The DOI matches its Crossref record; 145 of the 145 references it cites were found in a registry or an index; none of the 157 sources its claims cite is checked for support yet.
Drug induced liver injury – a 2023 update
Open accessAbstract
Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to as intrinsic, while if the injury occurs spontaneously, it is termed as idiosyncratic. This review predominately focused on idiosyncratic liver injury. The established molecular mechanisms for DILI include (1) mitochondria dysfunction, (2) increased reactive oxygen species levels, (3) presence of elevated apoptosis and necrosis, (4) and bile duct injuries associated with immune mediated pathways. However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown. Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed. The aim of this review was to utilize retrospective cohort studies from across the globe to gain insight into epidemiological patterns. This review considers (1) what is currently known regarding the mechanisms underlying DILI, (2) discusses potential risk factors and (3) implications of the coronavirus pandemic on DILI presentation and research. Future perspectives are also considered and discussed and include potential new biomarkers, causality assessment and reporting methods.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review updates understanding of drug-induced liver injury (DILI), focusing on idiosyncratic DILI (iDILI), its molecular mechanisms, global epidemiological patterns, risk factors, and clinical management. It concludes that mechanisms remain incompletely understood, diagnosis relies on exclusion and tools like RUCAM, and treatment is largely limited to withdrawing the offending drug.
Key findings
- DILI accounts for approximately 15% of acute liver failure cases in the United States and Europe, and roughly half of preclinical drugs with early evidence of hepatotoxicity are terminated before market authorization.
- Global incidence varies widely: 19.1 per 100,000 inhabitants in Iceland (amoxicillin-clavulanate most implicated at 22%, diclofenac 6%, azathioprine 4%, infliximab 4%, nitrofurantoin 4%), 13.9 (±2.4) per 100,000 in France, 2.4 per 100,000 person-years in the UK GPRD (1,636,792 individuals; 128 confirmed cases), 2.7 per 100,000 adults in Delaware (43% attributed to herbal dietary supplements, 36% to antibiotics), and 12 per 100,000 in South Korea (herbal medications 27.5%). Herbal medicines accounted for up to 53.63% of DILI in some Chinese cohorts, while antitubercular drugs (49%) and antiepileptics (12%) predominated in an Indian tertiary hospital, and ART (35%) and anti-TB drugs (27%) in South Africa.
- Among drugs implicated in iDILI, 61.1% are metabolized by CYP450 isoforms, 49.6% by CYP3A4/5 and 24.6% by CYP2C8/9; flucloxacillin-associated DILI is linked to HLA-B*57:01 (OR 80.6).
- Upon drug discontinuation, approximately 80% of DILI cases resolve spontaneously; about 20% develop chronic liver disease, DILI-related mortality is 5–10%, iDILI showed a 3-week transplant-free survival of 27%, and 5-year post-transplant survival in DILI-ALF patients is 70–80%.
Methods
- Narrative review with an extensive literature search of PubMed and Cochrane Library using terms including "Drug Induced Liver Injury," "DILI," "DILI mechanisms," "DILI incidence," "Idiosyncratic DILI," "DILI causality assessment," "Drug Injury" and "Drug Discovery"; last search conducted 16 May 2023.
- Exclusion criteria were publications focused on hepatic injury primarily from alcohol and studies of autoimmune hepatitis; paracetamol-induced injury was excluded from the global incidence review to focus on idiopathic DILI.
- No new data were created or analyzed (per the data availability statement); the review synthesizes retrospective cohort studies, registry data, and meta-analysis findings.
Limitations
- Stated: the authors note that due to the "inevitable limitations and exclusionary nature of any literature search," investigations that did not include the search terms in the title or lacked adequate abstract information might have been unintentionally omitted.
- Stated: findings across incidence studies are difficult to compare directly because diagnostic parameters, cohort demographics, and regional prescribing/epidemiological patterns differ.
- Evident from the text: the review is narrative rather than systematic, and several cited incidence figures derive from single-hospital or single-region retrospective studies with differing biochemical thresholds (e.g., ALT > 3× ULN vs. ALT > 10× ULN), limiting generalizability.
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Claims the paper makes
134 Sources not found · 61 Own interpretation · 3 No basis given · 1 Not checked yet
In the paper
“Drug metabolism enzymes and transporters-particularly cytochrome P450 enzymes (CYP450) – convert drugs into metabolites through bioactivation (Russmann, Kullak-Ublick, and Grattagliano Citation2009).”
What the sources say
- Not matchedcites Russmann, Kullak-Ublick, and Grattagliano Citation2009
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In the paper
“Drug metabolites may bind either covalently or non-covalently bind to CYP450 enzymes creating a hapten-like drug-protein adduct (Villanueva-Paz et al. Citation2021).”
What the sources say
- Not matchedcites Villanueva-Paz et al. Citation2021
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In the paper
“It is noteworthy that while there are shared mechanisms, acute DILI and immune-mediated DILI are usually distinct in their clinical presentation and prognosis.”
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“In iDILI, it is understood that activation of T lymphocytes is a critical process in hepatocellular damage.”
What the sources say
- Not matchedcites Gerussi et al. Citation2021
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In the paper
“T cells are activated when antigen-presenting cells (APCs) present drug antigens or drug-modified self-antigens to these cells (Gerussi et al. Citation2021).”
What the sources say
- Not matchedcites Gerussi et al. Citation2021
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In the paper
“The inflammatory response is also enhanced by excess production of ROS in both processes.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Findings are difficult to directly compare as various diagnostic parameters were employed, cohort demographics varied and epidemiological differences in prescriptions and drug uses contribute to varying contrasting results.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Both types of injury involve release of cascade of pro-inflammatory cytokines (Tasnim et al. Citation2021).”
What the sources say
- Not matchedcites Tasnim et al. Citation2021
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plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Antigens connected to bile duct epithelial cells may be recognized by CD4+ T lymphocytes, triggering an immunological response and production of cytokines that initiate bile duct damage.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Dysfunction of the hepatic mitochondria might occur when reactive metabolites disrupt complexes involved in the mitochondrial electron transport chain, leading to an increased formation of ROS, which is a consequence of electrons prematurely reacting with molecular oxygen (Russmann, Kullak-Ublick, and Grattagliano Citation2009).”
What the sources say
- Not matchedcites Russmann, Kullak-Ublick, and Grattagliano Citation2009
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hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“DILI may be classified as either predictable (intrinsic) or spontaneous (idiosyncratic) with the latter being associated with the most reported clinical presentations (Katarey and Verma Citation2016).”
What the sources say
- Not matchedcites Katarey and Verma Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“Alternatively, chemically inert drugs may form non-covalent interactions with MHC II complexes, altering their binding pocket and encouraging an immune response (Kubes and Jenne Citation2018).”
What the sources say
- Not matchedcites Kubes and Jenne Citation2018
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In the paper
“These hapten-like drug-protein adducts might bind to endogenous proteins to form neoantigen structures that are presented to CD8+ cytotoxic T-Cells via MHC II complexes initiating upregulation of transcription factors Fas and TNF-α which ultimately lead to cell death after immune cell recruitment (Gerussi et al. Citation2021).”
What the sources say
- Not matchedcites Gerussi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“For example, investigations conducted in Africa demonstrated that the most common cause of DILI was due to anti-tuberculosis and anti-retroviral drugs utilization (Amadi and Orisakwe Citation2018; Riebensahm et al. Citation2019).”
What the sources say
- Not matchedcites Amadi and Orisakwe Citation2018
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- Not matchedcites Riebensahm et al. Citation2019
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boostedstates a cause- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In acute DILI, reactive metabolites may directly induce misfolded proteins resulting in unfolded protein response (UPR).”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Host factors such as age, gender, genetic polymorphisms, lifestyle, and immune status may also contribute to the adverse drug reaction (Villanueva-Paz et al. Citation2021).”
What the sources say
- Not matchedcites Villanueva-Paz et al. Citation2021
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In the paper
“Intrinsic reactions are less common, have a shorter latency period and are often described as being predictable, dose-dependent and reproducible in animal models (Yokoi and Oda Citation2021).”
What the sources say
- Not matchedcites Yokoi and Oda Citation2021
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plainstates an association- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DAMPs are released upon hepatocyte damage and initiate further inflammation.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Villanueva-Paz et al. (Citation2021) proposed that inhibition of BSEPs was a common mechanism underlying drug-induced cholestasis as it is understood that retention of bile acid contributes to hepatocellular stress.”
What the sources say
- Not matchedcites Villanueva-Paz et al. Citation2021
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it is postulated that multiple factors determine the immune-mediated response to a drug or its metabolite and this may account for the rarity in these types of injuries.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Drug induced hepatic injury may be the result of direct toxicity from xenobiotics or their metabolites or indirectly through an aberrant immune system response (Gerussi et al. Citation2021).”
What the sources say
- Not matchedcites Gerussi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“DILI is a significant concern in preclinical drug development and a leading cause of candidate drug attrition (Korver et al. Citation2021).”
What the sources say
- Not matchedcites Korver et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Garcia-Cortes et al. (Citation2020) indicated that frequently used drugs thought to be associated with an immune response include halothane, sulindac, sulfamethoxazole, chlorpromazine, flucloxacillin and amoxicillin-clavulanate.”
What the sources say
- Not matchedcites Garcia-Cortes et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Autoantibodies or drug-induced antibodies may combine with bile duct epithelial cells to generate immune complexes that activate complement and damage the bile duct.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“DILI accounts for approximately 15% of cases of acute liver failure in the United States and Europe (Reuben et al. Citation2010).”
What the sources say
- Not matchedcites Reuben et al. Citation2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Endoplasmic reticulum stress is reported as a later event within metabolic dysfunction and is thought to occur due to (1) an over-accumulation of ROS, (2) an imbalance in intracellular Ca2+ levels and (3) activation of the unfolded protein response (Zhang et al. Citation2020).”
What the sources say
- Not matchedcites Zhang et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Drug lipophilicity is positively associated with DILI risk as this might stimulate hepatocyte absorption, resulting in toxic levels of reactive metabolites (Teschke and Danan Citation2021a).”
What the sources say
- Not matchedcites Teschke and Danan Citation2021a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“The elevation in ROS levels activates mitochondrial permeability transition pores which further enhances ROS production and leads to mitochondrial swelling, apoptosis or necrosis (Yan et al. Citation2018).”
What the sources say
- Not matchedcites Yan et al. Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Further, bile salts accumulate due to medication or reactive metabolite blockage of the BSEP, which induces inflammation and immune-mediated bile duct damage (Grewal and Ahmad Citation2019).”
What the sources say
- Not matchedcites Grewal and Ahmad Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, sustained cytotoxic activity may lead to ER-induced stress (Björnsson and Björnsson Citation2022).”
What the sources say
- Not matchedcites Björnsson and Björnsson Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In parallel, pro-inflammatory cytokines are released by CD4+ helper T cells and other immune cells, including macrophages, which further promote inflammation and subsequent hepatic injury.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Pyroptosis is an inflammatory cell death mechanism (cells under stress conditions, upregulate Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes) resulting in activation of caspase which was found to damage hepatic cells and augment organ inflammation (Luan and Ju Citation2018; Szabo and Petrasek Citation2015).”
What the sources say
- Not matchedcites Luan and Ju Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Szabo and Petrasek Citation2015
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In the paper
“On the other hand, idiosyncratic reactions are not predictable, not dose-dependent, exhibit variable latency and are not reproducible experimentally in animal models (Fontana et al. Citation2023; Hosack, Damry, and Biswas Citation2023; Yokoi and Oda Citation2021).”
What the sources say
- Not matchedcites Fontana et al. Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Hosack, Damry, and Biswas Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Yokoi and Oda Citation2021
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plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Hepatic injuries are associated with one or more molecular pathways in response to xenobiotic compounds administration and vary between individuals depending upon host factors which makes predicting adverse drug reactions very difficult (McGill and Jaeschke Citation2018).”
What the sources say
- Not matchedcites McGill and Jaeschke Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In direct injury toxic metabolites might overwhelm hepatic cells leading to an immune response, whereas immune-mediated DILI might occur without an accumulation of metabolites as immune mechanisms mistakenly identify drug-altered hepatic cells as foreign.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Acute DILI is associated with recent drug exposure and may resolve quickly upon discontinuation of the offending agent, whereas immune-mediated DILI might be chronic requiring immunosuppressive treatment.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hepatocytes are then directly injured and undergo apoptosis due to CD8+ cytotoxic T cells activation.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Direct drug-mediated toxicity, intracellular organelle stress, or hepatocyte membrane damage might activate cell signaling pathways that results in apoptosis or necrosis (Krishna Citation2017).”
What the sources say
- Not matchedcites Krishna Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hepatocyte injury is initiated by an increase in oxidative stress resulting from ROS imbalance, endoplasmic reticulum stress, ATP depletion, mitochondrial dysfunction, calcium overload, glutathione depletion, protein dysfunction and BSEP inhibition.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inflammation plays a key role in both types of injury.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Bile duct injuries are thought to be the result of T-cell mediated hypersensitivity but might also occur as biliary epithelium is directly exposed chemically reactive metabolites (CRMs) which are excreted following biotransformation (Grewal and Ahmad Citation2019).”
What the sources say
- Not matchedcites Grewal and Ahmad Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, in immune-mediated DILI the elevated levels of pro-inflammatory cytokines might alter ER function.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The molecular mechanisms that are involved in T-cell response in DILI are described by the pharmacological interaction p-i model”
What the sources say
- Not matchedcites Adair, Meng, and Naisbitt Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Gerussi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Pichler Citation2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The established molecular mechanisms for DILI include (1) mitochondria dysfunction, (2) increased reactive oxygen species levels, (3) presence of elevated apoptosis and necrosis, (4) and bile duct injuries associated with immune mediated pathways.”
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Immune-mediated injuries occur when a hypersensitivity reaction provokes an inflammatory response that involves both the innate and adaptive immune systems (Lee and Lawrence Citation2018).”
What the sources say
- Not matchedcites Lee and Lawrence Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Approximately half of preclinical drugs with early evidence of hepatotoxicity are terminated prior to achieving market authorization (McGill and Jaeschke Citation2019).”
What the sources say
- Not matchedcites McGill and Jaeschke Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“In addition, the interaction of parental or metabolized drugs with T-cell receptors and MHC II and antigen interactions leads to activation of CD8+ cytotoxic cells and CD4+ helper cells which both play key role in idiosyncratic DILI.”
What the sources say
- Not matchedcites Adair, Meng, and Naisbitt Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Gerussi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Damage-associated molecular patterns are known to bind to toll-like receptors (TLRs) and purinergic receptors expressed by KCs which secrete an array of pro-inflammatory mediators such as IL6, IL18, TNF-α, IFN-Y and Fas ligands which further drive the proliferation of macrophages (Katarey and Verma Citation2016).”
What the sources say
- Not matchedcites Katarey and Verma Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is not surprising that in countries with a higher usage of a particular compound there tends to be higher incidences of DILI attributed to those specific drugs.”
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“The altered peptide repertoire hypothesis suggests that drugs may induce mistargeting of endogenous peptides leading to HLA autoimmunity (Segovia-Zafra et al. Citation2021).”
What the sources say
- Not matchedcites Segovia-Zafra et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While acute DILI and immune-mediated DILI display distinct underlying causes, there are shared molecular mechanisms that contribute to hepatic injury in both presentations.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reactive metabolites might also activate the immune response via drug-protein adducts, haptens, TLR binding, mistargeting of peptides, MHC II binding release of pro-inflammatory cytokines in a positive loop with upregulation of the recruitment of additional immune cells.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BSEP inhibition may lead to bile duct injuries such as obstruction, accumulation of bile salts and interference in sinusoidal uptake.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Injuries of the bile duct present in cholestatic or mixed liver injuries and are characterized by the destruction of biliary epithelium which leads to biliary cirrhosis (Eiswerth et al. Citation2022).”
What the sources say
- Not matchedcites Eiswerth et al. Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“DILI occurs when drug metabolism is altered and results in hepatic damage attributed to oxidative stress, inflammatory damage, apoptosis, necrosis or mitochondrial membrane breakdown and organ dysfunction (Garcia-Cortes et al. Citation2020).”
What the sources say
- Not matchedcites Garcia-Cortes et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ER stress is another shared mechanism in both presentations, but the specific triggers and pathways involved vary between the two conditions.”
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Fisher, Vuppalanchi, and Saxena (Citation2015) reported similar evidence and shared that valproate and aspirin were frequent agents associated with DILI in children, whereas amoxicillin-clavulanate was the most frequent causative agent in those over 50.”
What the sources say
- Not matchedcites Fisher, Vuppalanchi, and Saxena Citation2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“This hypothesis considers that most of these drugs are metabolized to acyl glucuronides that freely undergo excretion (Teschke and Danan Citation2021a).”
What the sources say
- Not matchedcites Teschke and Danan Citation2021a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinical intervention may often be delayed due to a lack of specific symptoms and lab testing.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“This allele has been implicated in many DILI cases (OR 80.6); and therefore, it is prudent to carry out HLA genetic testing when treating patients with these types of injuries (Ahmad and Odin Citation2017).”
What the sources say
- Not matchedcites Ahmad and Odin Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“RUCAM has been frequently utilized since its inception in 1993 (Danan and Benichou Citation1993).”
What the sources say
- Not matchedcites Danan and Benichou Citation1993
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are numerous proposed risk factors for occurrence of iDILI or specific types of injury, which include but not limited to age, biological gender, genetics, preexisting disease state and drug characteristics.”
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“With DILI symptoms being nonspecific, clinical assessment methods are frequently employed to diagnose cases (Björnsson Citation2021; European Association for the study of the liver 2019).”
What the sources say
- Not matchedcites Björnsson Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites European Association for the study of the liver 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Elsewhere, symptomatic drug-induced injuries were investigated in France between 1997 and 2000 by Sgro et al. (Citation2002) who reported that anti-microbials (19%) and non-steroidal anti-inflammatory drugs (NSAIDs) (16%) were associated with the highest incidence of DILI.”
What the sources say
- Not matchedcites Sgro et al. Citation2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Multiple drugs are frequently prescribed concurrently to treat several diseases and patients may take numerous drugs for their condition. This makes isolation of the offending agent increasingly difficult.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“However, it was concluded that neither old age nor female gender were pre-disposing factors to DILI overall, but rather a determinant for cholestatic injury with male dominance.”
What the sources say
- Not matchedcites Lucena et al. Citation2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“The MHC consists of more than 200 genes on chromosome 6 and a total of over 1500 alleles of the HLA-B gene were identified (Perwitasari et al. Citation2018).”
What the sources say
- Not matchedcites Perwitasari et al. Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“It is an interesting that almost all drugs with black box warnings have a daily dosage of >50 mg (Vuppalanchi et al. Citation2014).”
What the sources say
- Not matchedcites Vuppalanchi et al. Citation2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In 2015, the Drug-Induced Liver Injury Network (DILIN) also stated that older age was not an overall risk factor for DILI but corroborates that older age is associated with cholestatic injury, especially resulting from amoxicillin-clavulanate, isoniazid and nitrofurantoin exposure (Chalasani et al. Citation2015).”
What the sources say
- Not matchedcites Chalasani et al. Citation2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“An Icelandic study of patients with a DILI diagnosis from 2010 to 2011 using the Roussel Uclaf Causality Assessment Method (RUCAM) assessment method found amoxicillin-clavulanate to be the most implicated agent at 22% of DILI patients, followed by diclofenac (6%), azathioprine (4%), infliximab (4%) and nitrofurantoin (4%) (Björnsson et al. Citation2013).”
What the sources say
- Not matchedcites Björnsson et al. Citation2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a causen = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“CRMs generated by CYP450 enzymes produce cellular stress and an association was identified between covalent binding and the risk of iDILI occurrence.”
What the sources say
- Not matchedcites Jee, Sernoskie, and Uetrecht Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it is worth mentioning that the ULN sometimes varies between different labs, which markedly alters the calculation.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Teschke and Danan (Citation2021a) identified 61.1% of drugs implicated in iDILI being metabolized by CYP450 isoforms. Among these pharmaceuticals, almost half (49.6%) were shown to be metabolized by CYP3A4 and 5 and almost quarter (24.6%) were catabolized by CYP2C8 or 9 (Teschke and Danan Citation2021a).”
What the sources say
- Not matchedcites Teschke and Danan Citation2021a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In an Indian tertiary hospital studied 82 suspected DILI patients from 2014 to 2015 were detected and the most frequently implicated drugs were antitubercular therapy drugs (49%) and antiepileptic drugs (12%) (Rathi et al. Citation2017).”
What the sources say
- Not matchedcites Rathi et al. Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 82- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“The method is a diagnostic tool based upon seven clinical observations that provide a framework for diagnosis and evaluation (Jee, Sernoskie, and Uetrecht Citation2021).”
What the sources say
- Not matchedcites Jee, Sernoskie, and Uetrecht Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Surprisingly, 43% of cases were attributed to herbal dietary supplements (HDS), while 36% were due to antibiotics (Vega et al. Citation2017).”
What the sources say
- Not matchedcites Vega et al. Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a causen = 20- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“The Biopharmaceutics Drug Disposition Classification System (BDDCS) evaluates the severity of DILI warning drug labels. The system is a four-class approach based on water solubility and extent of metabolism.”
What the sources say
- Not matchedcites Bocci, Oprea, and Benet Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“In another study, Fisher, Vuppalanchi, and Saxena (Citation2015) suggested that females are not at an increased risk but are more likely to progress to acute liver failure, indicating that females are likely to exhibit worsened prognosis once DILI has occurred.”
What the sources say
- Not matchedcites Fisher, Vuppalanchi, and Saxena Citation2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ideally, a functional biomarker needs exhibit high sensitivity and specificity (>90%) to achieve a high Positive Predictive Value and Negative Predictive Value (70–80%).”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Elevations in activities of ALT, AST and ALP, and total bilirubin content are most frequently used for detection but do not reliably correlate with the degree of hepatic impairment, and do not show good prognostic value (McGill and Jaeschke Citation2018).”
What the sources say
- Not matchedcites McGill and Jaeschke Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“The highest risk of hepatotoxicity occurred with azathioprine (0.75%) and infliximab (0.68%), and the population-based incidence of idiopathic DILI was 19.1 per 100,000 inhabitants (Björnsson et al. Citation2013).”
What the sources say
- Not matchedcites Björnsson et al. Citation2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a causen = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Physicians may face further issues in discontinuing the offending agent as doing so may worsen the patient’s other co-morbidities.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Chalasani et al. (Citation2015) presented conflicting data regarding the female gender being an enhanced risk factor for DILI where a higher prevalence of females (59%) was noted.”
What the sources say
- Not matchedcites Chalasani et al. Citation2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Increased lipophilicity of a compound leads to increased permeability and uptake and increased levels of biotransformation and subsequent higher concentrations of toxic metabolites (Teschke and Danan Citation2021a).”
What the sources say
- Not matchedcites Teschke and Danan Citation2021a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“RUCAM provides (1) possible causative agent in the case of multiple drug administration, (2) unpredictability idiosyncratic liver events and (3) lack of diagnostic biomarkers inferring that clinical recognition is still troublesome (Hosack, Damry, and Biswas Citation2023).”
What the sources say
- Not matchedcites Hosack, Damry, and Biswas Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Clinical testing is useful for the detection of DILI but is not indicative of prognosis or etiology (McGill and Jaeschke Citation2019).”
What the sources say
- Not matchedcites McGill and Jaeschke Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In a 2016 genome-wide study, the most significant single nucleotide polymorphisms identified were rs114577328 in the major histocompatibility complex (MHC) region of chromosome 6 and rs72631567 on chromosome 2 (Nicoletti et al. Citation2016).”
What the sources say
- Not matchedcites Nicoletti et al. Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Symptoms may mimic other hepatic disorders such as autoimmune hepatitis which emphasizes the need for DILI diagnosis by exclusion.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: DILI diagnosis requires exclusion of other hepatic disorders.
In the paper
“Similarly, a study carried out in 2009 at a hospital in South Africa showed the highest risk for DILI was antiretroviral therapy (ART) (35%) followed by anti-TB drugs (27%) (Schutz et al. Citation2012).”
What the sources say
- Not matchedcites Schutz et al. Citation2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Data seem to further suggest that immune-checkpoint inhibitors for HIV treatment are a significant enhanced risk for liver injury (Real et al. Citation2019).”
What the sources say
- Not matchedcites Real et al. Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In this study, patients aged 60+ accounted for 46% of cases with no cases recorded in the 20–29-year group (Lucena et al. Citation2009).”
What the sources say
- Not matchedcites Lucena et al. Citation2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“LiverTox (LiverTox Citation2022) is another multilayered and interactive website with evidence-based information on drug, dietary supplements, and herbal-induced liver injury.”
What the sources say
- Not matchedcites LiverTox Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Younger age was associated with cytolytic damage with a female over-representation (Lucena et al. Citation2009).”
What the sources say
- Not matchedcites Lucena et al. Citation2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“However, recently some issues have been raised regarding the appropriateness of this database as a means of predicting iDILI fundamentally due to concerns with factors such as quality of data, lack of evidence-based case studies and absence of standard definitions and categorization of liver injury itself (Teschke and Danan Citation2021b).”
What the sources say
- Not matchedcites Teschke and Danan Citation2021b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“ART/TB drugs and herbal compounds exhibit a significantly higher prevalence within the Eastern world, whereas antibiotics, NSAIDs and psychotropic drugs display a higher prevalence in the Western world (Low et al. Citation2020).”
What the sources say
- Not matchedcites Low et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Data demonstrated a crude incidence rate of 2.4 per 100,000 person-years with the strongest drug associations consisting of anti-microbials (amoxicillin-clavulanic acid, flucloxacillin, macrolides, tetracyclines) and NSAIDs (De Abajo et al. Citation2004).”
What the sources say
- Not matchedcites De Abajo et al. Citation2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“A common HLA allele present in patients with DILI administered amoxicillin-clavulanate is HLA-DRB1 × 15 and HLA-DRB1 × 06.”
What the sources say
- Not matchedcites Ahmad and Odin Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further, there is no official recommendation for scenarios with preexisting liver impairment or abnormal baseline serum enzyme activity levels.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“It is believed that sex hormones are important in regulation of drug metabolism, transport and dimorphism in cellular stress pathways (Wang et al. Citation2021).”
What the sources say
- Not matchedcites Wang et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“It has been demonstrated that flucloxacillin (an antibiotic widely used for staphylococcal infection) is a frequent cause of DILI and is associated with HLA-B × 57:01 (Ahmad and Odin Citation2017).”
What the sources say
- Not matchedcites Ahmad and Odin Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HLA genotyping is now widely accessible, affordable and might assist with diagnosis.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Recently, Teschke and Danan (Citation2020) found that the RUCAM model was used to assess possible cases of idiosyncratic DILI in 81,856 published reports listed on PubMed since 1993.”
What the sources say
- Not matchedcites Teschke and Danan Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“With the BDDCS, it is possible to predict the role of metabolic transporters and enzymes to calculate the new molecular entity prior to its administration to animals or humans (Bocci, Oprea, and Benet Citation2022).”
What the sources say
- Not matchedcites Bocci, Oprea, and Benet Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“De Valle et al. (Citation2006) found that DILI occurred more often in women and antibiotics were the most frequent agent (30%) followed by diclofenac (22%).”
What the sources say
- Not matchedcites De Valle et al. Citation2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an associationn = 77- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Recently, the FDA announced support for further clinical exploration of novel biomarkers microRNA-122 and glutamate dehydrogenase (Andrade et al. Citation2019).”
What the sources say
- Not matchedcites Andrade et al. Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In summary, RUCAM is a well established and trusted system of assigning points for clinical and biochemical features of liver injury which provides an overall assessment score indicating the likelihood of hepatic injury is due to the specific drug in question (Danan and Teschke Citation2016).”
What the sources say
- Not matchedcites Danan and Teschke Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“HLA encodes for components of the MHC which are involved in immune processes that occur during DILI (Ahmad and Odin Citation2017) via surface proteins that bind to foreign molecules to elicit an immune response.”
What the sources say
- Not matchedcites Ahmad and Odin Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“On the other hand, drugs with a carboxylic acid functional group may be associated with a lower risk of iDILI occurrence.”
What the sources say
- Not matchedcites Teschke and Danan Citation2021a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In contrast, another study originating in China reported similar findings to western countries and noted antimicrobial incidence at 32% and glucocorticoids at 24% (Xu et al. Citation2012).”
What the sources say
- Not matchedcites Xu et al. Citation2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Sgro et al. (Citation2002) also noted an annual incidence of 13.9% (±2.4%) per 100,000 inhabitants.”
What the sources say
- Not matchedcites Sgro et al. Citation2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In 2011, the International Serious Adverse Events Consortium set biochemical thresholds at ALT or AST ≥ 5× ULN and ALP > 2 ULN which helps to provide a baseline reference for physicians (Jee, Sernoskie, and Uetrecht Citation2021).”
What the sources say
- Not matchedcites Jee, Sernoskie, and Uetrecht Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Suk et al. (Citation2012) focused on hospitals in South Korea from 2005 to 2007 and noted an incidence of 12 per 100,000 inhabitants with the frequent causative agents being herbal medications (27.5%).”
What the sources say
- Not matchedcites Suk et al. Citation2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“A total of 1164 cases were analyzed leading to a DILI diagnosis in 77 cases (6.6%).”
What the sources say
- Not matchedcites De Valle et al. Citation2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 77- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Other biomarkers may be analyzed during diagnosis (acetaminophen-cysteine protein adducts), prediction (genetic markers), and prognosis (micro-RNA-122, keratin-18, glutamate dehydrogenase and mtDNA) (McGill and Jaeschke Citation2019).”
What the sources say
- Not matchedcites McGill and Jaeschke Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Taking this into account, it has been suggested that glutamate dehydrogenase might be a more specific marker of liver injury as compared to ALT (Clinton et al. Citation2021).”
What the sources say
- Not matchedcites Clinton et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Although preexisting liver disease is not necessarily an enhanced risk factor for DILI, these patients have been found to have a significantly higher risk of morbidity (Chalasani et al. Citation2015).”
What the sources say
- Not matchedcites Chalasani et al. Citation2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Further, in an Icelandic investigation, Björnsson et al. (Citation2013) suggested that there was a 3-fold increased risk of DILI in older patients, although this may be attributed to higher prescription rates in the elderly.”
What the sources say
- Not matchedcites Björnsson et al. Citation2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Further, in a study conducted in Delaware (USA) via surveillance of DILI symptoms during 2014, an incidence rate of 2.7 per 100,000 adult residents was detected (Vega et al. Citation2017).”
What the sources say
- Not matchedcites Vega et al. Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 20- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, it stands to reason that there is an increased health risk attributed toxic compounds exposure including drugs in patients with a metabolically compromised liver.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“From 1998 to 2009 there was a 43% reduction in paracetamol-related death and a 61% fall in liver transplant following paracetamol overdose (Hawton et al. Citation2013).”
What the sources say
- Not matchedcites Hawton et al. Citation2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“There is also a reported association between the microbiome of the gut and immune mediated DILI, particularly with the use of isoniazid when treating tuberculosis (Liu et al. Citation2023).”
What the sources say
- Not matchedcites Liu et al. Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DILI treatment has remained relatively unchanged for decades.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In 2023, metabolic dysfunction-associated steatotic liver disease (MASLD) (formally known as nonalcoholic fatty liver disease) displayed a high prevalence affecting 25% of the global population (McPherson et al. Citation2022), amongst whom nearly 30% progressed to metabolic dysfunction-associated steatohepatitis (MASH) (formally known as nonalcoholic steatohepatitis).”
What the sources say
- Not matchedcites McPherson et al. Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At present, there are no approved therapies to manage MASLD.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“In severe cases, high dose use of tocilizumab, an IL-8 inhibitor is utilized to manage the cytokine storm in COVID-19 patients (Muhović et al. Citation2020; Vitiello et al. Citation2021).”
What the sources say
- Not matchedcites Muhović et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Vitiello et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Most cases of ALF in the Western world are produced by intrinsic DILI (paracetamol) (Chan and Benet Citation2017).”
What the sources say
- Not matchedcites Chan and Benet Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The organs implicated most commonly in SJS are the liver and skin with severe cutaneous adverse reactions (Ortega-Alonso et al. Citation2016).”
What the sources say
- Not matchedcites Ortega-Alonso et al. Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hepatoprotective medications including N-acetylcysteine and L-carnitine may be used as an antidote, but these are only indicated for intrinsic DILI.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment is aimed at detoxification, scavenging free radicals, anti-oxidation, hepatocyte protection and immune regulation.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Treatment of DILI is aimed at detoxification, scavenging free radicals, anti-oxidation, hepatocyte protection and immune regulation.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Evidence indicates that an important consideration from the scrutiny of the literature is that shortage of animal models exists that accurately capture iDILI, although a number of promising candidates do exist such as inflammagen model (Segovia-Zafra et al. Citation2021) or the Uetrecht-Pohl model (Gerussi et al. Citation2021).”
What the sources say
- Not matchedcites Segovia-Zafra et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Gerussi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar observations were found when anti-viral drugs were applied prophylactically, leading to subsequent liver damage.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“It is now estimated that 2 out of every 3 adults in the UK exhibit early stages of MASLD.”
What the sources say
- Not matchedcites British Liver Trust Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immune mediated DILI may benefit from a course of corticosteroids.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As discussed, numerous investigations noted a link between DILI and polymorphisms of certain HLA genotypes as well as CYP450s; yet more investigations of better understanding of the mechanisms underlying DILI/iDILI are urgently needed.”
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Recent clinical practice guidelines have agreed that liver transplantation is still the primary resolution for severe ALF (Devarbhavi et al. Citation2021; Andrade et al. Citation2019).”
What the sources say
- Not matchedcites Devarbhavi et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Andrade et al. Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The precise pathophysiological mechanism related to COVID is not yet fully understood, but current theories are centered on direct viral injury, treatment-related DILI and immune-mediated injury, where SARS-CoV-2 infect hepatocytes, directly via the angiotensin-converting enzyme 2 receptor, which the virus uses to infiltrate respiratory tissue cells.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The classification of injury needs to be determined as this dictates the treatment plan to follow.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The prompt identification and discontinuation of the offending agent is crucial in early DILI management.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“SJS is associated with immune-mediated DILI and patients with both SJS and DILI concurrently exhibit a higher risk of morbidity (Andrade et al. Citation2019).”
What the sources say
- Not matchedcites Andrade et al. Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“He, Morales, and Gutherie (Citation2020) reported that of a total of 305 investigated trials a third of the studies were at high risk of bias, most frequently because the clinical population used was not appropriate for the trial examined.”
What the sources say
- Not matchedcites He, Morales, and Gutherie Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Several investigators suggested that xenobiotic-induced adverse effects in the liver are aggravated in the diseased organ (Allard et al. Citation2021; Kermanizadeh et al. Citation2017, Citation2022; Lammert et al. Citation2019; Li, Gao, and Niu Citation2019; Vargas et al. Citation2017).”
What the sources say
- Not matchedcites Allard et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Kermanizadeh et al. Citation2017, Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Lammert et al. Citation2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Liver injury in mild cases of COVID-19 is usually reversible.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“A frequently utilized treatment for cholestatic injury is ursodeoxycholic acid which is a naturally occurring hydrophilic bile acid that decreases cholesterol saturation index of bile (Li et al. Citation2022; Robles-Diaz et al. Citation2021).”
What the sources say
- Not matchedcites Li et al. Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Robles-Diaz et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“iDILI is one of the more challenging forms of liver disease, both in terms of diagnosis and management.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Importantly, 96% of adults with MASLD in the United States were unaware that these individuals were suffering from liver disease (Alqahtani et al. Citation2021).”
What the sources say
- Not matchedcites Alqahtani et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In more severe injuries, a liver biopsy may be required to determine injury type and prognosis.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The exposure to xenobiotics might aggravate preexisting liver conditions, related to the growing obesity pandemic, western diet and sedentary lifestyle.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In one study, iDILI showed a 3-week transplant-free survival rate of just 27% (Ostapowicz et al. Citation2002).”
What the sources say
- Not matchedcites Ostapowicz et al. Citation2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Biochemical tests may aid diagnosis but are not reliably indicative of severity or prognosis (Rathi et al. Citation2017).”
What the sources say
- Not matchedcites Rathi et al. Citation2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is a particular issue in the treatment of TB where no alternative therapies are available.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Liver support devices such as hemodialysis and use of a Molecular Adsorbent Recirculating System (MARS) might replicate the detoxifying function of the liver and thus stabilize the patient’s health while awaiting transplant (Adam et al. Citation2018).”
What the sources say
- Not matchedcites Adam et al. Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Although the most common experimental animal models (particularly mice) express homologs of the major CYP450s in humans, not all those homologs possess the same substrate specificity (Turpeinen et al. Citation2007); hence, there is an overall poor human response predictivity.”
What the sources say
- Not matchedcites Turpeinen et al. Citation2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Approximately 20% of DILI patients develop chronic liver disease (Wang et al. Citation2021)”
What the sources say
- Not matchedcites Wang et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Assuming that clinically asymptomatic MASLD might render patients under medication to a higher risk for developing liver injury, then this cohort is clearly underrepresented in clinical safety studies.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- The authors state this as an assumption: Clinically asymptomatic MASLD might render patients under medication to a higher risk for developing liver injury.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inhibition of CYP3A4 enzyme activity and liver transporter proteins are suspected as being important factors leading to disruption of drug metabolism and subsequent manifestation of DILI.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Inhibition of CYP3A4 enzyme activity and liver transporter proteins are important factors leading to disruption of drug metabolism and subsequent manifestation of DILI.
In the paper
“Of note, in 2016, the USA’s economic burden of chronic liver diseases was $32.5 billion, with over 65% of spending on inpatient or emergency care, while in 2020, the clinical cost of liver disease in the UK alone was reported to be over £10 billion, accounting for 5% of the national health service budget (NHS Citation2023).”
What the sources say
- Not matchedcites NHS Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“large cohort studies reported DILI-related mortality to be 5–10% (Björnsson Citation2021)”
- Also stated in: § Methods · plain
“Large studies found DILI mortality rates to be approximately 5–10% and transplant is usually considered if symptoms progress to ALF.”
What the sources say
- Not matchedcites Björnsson Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Methods · plain
In the paper
“Activated charcoal may provide therapeutic benefits, but its administration is restricted to within 3–4 hr since consumption (Hosack, Damry, and Biswas Citation2023).”
What the sources say
- Not matchedcites Hosack, Damry, and Biswas Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metabolic liver diseases and exposure to xenobiotics might trigger similar cellular stress responses, with the capability to stimulate and accelerate further disease progression.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A rare complication occurs when Stevens-Johnson Syndrome (SJS) occurs concurrently with DILI.”
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Investigators demonstrated that while the female gender and increased age are not necessarily a risk factor for DILI overall, these demographics are more likely to lead to certain types of injury and greater risk of mortality.”
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Mortality rates for liver disease have increased 400% since 1970, and in individuals aged younger than 65 years, mortality frequencies have risen almost 500% (British Liver Trust Citation2023).”
What the sources say
- Not matchedcites British Liver Trust Citation2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“In this scenario, re-challenge strategies may be implemented with the aim of desensitizing patient reaction (Stine and Lewis Citation2016).”
What the sources say
- Not matchedcites Stine and Lewis Citation2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, severe cases have required medical attention where liver functions are closely monitored and treated with hepatoprotective, anti-inflammatory agents such as glycyrrhizic acid, bicyclol and polyene phosphatidyl choline to diminish cytopathic effects of virus on the hepatocytes to reduce liver damage.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“This direct infection results in liver injury, inflammation, cellular damage, treatment-related DILI and immune-mediated injury (Clinton et al. Citation2021; Marjot et al. Citation2021; McGrowder et al. Citation2021).”
What the sources say
- Not matchedcites Clinton et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Marjot et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites McGrowder et al. Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Several investigators proposed that patients fighting an active COVID-19 infection may be relatively immunodeficient; however, when being treated with an array of drugs, the consequence is a greater risk of developing immune-mediated DILI (Bonaventura et al. Citation2020; Hui et al. Citation2020; Lu, Stratton, and Tang Citation2020; Naseralallah et al. Citation2022; Xie et al. Citation2020).”
What the sources say
- Not matchedcites Bonaventura et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Hui et al. Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Lu, Stratton, and Tang Citation2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Proactive measures may be taken for recent ingestion such as in the case of paracetamol overdose.”
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Immune-checkpoint inhibitor (ICI) in hepatitis is rare, but cases are increasing as use of novel ICIs and combination with other chemotherapy drugs are being prescribed to oncology patients (Björnsson Citation2021).”
What the sources say
- Not matchedcites Björnsson Citation2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Another frequently employed pharmacotherapy is bicyclol, an inflammatory cytokine inhibitor that suppresses activity of various necrosis factors and interleukins (Adam et al. Citation2018).”
What the sources say
- Not matchedcites Adam et al. Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diagnosis is made further difficult as DILI follows diagnosis by exclusion.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: DILI diagnosis requires exclusion of other hepatic disorders.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unfortunately, a significant issue in treating DILI is that the therapeutic effect of the offending agent is lost upon the de-challenge.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In a recent investigation, Saha, Vij, and Rawat (Citation2022) using liver biopsies taken from COVID-19 patients showed microvesicular steatosis, patchy necrosis and infiltration of lymphocytes.”
What the sources say
- Not matchedcites Saha, Vij, and Rawat Citation2022
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Studies indicate a 5-year post-transplant survival rate between 70% and 80% in DILI-ALF patients (Adam et al. Citation2018).”
What the sources say
- Not matchedcites Adam et al. Citation2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper relies on this without support.
Incidences of DILI occur frequently.
“Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed.”
The paper relies on this without support.
Treatment options are limited once DILI has developed.
“Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed.”
The paper relies on this without support.
The cited retrospective cohort studies are representative of global DILI epidemiology.
“The aim of this review was to utilize retrospective cohort studies from across the globe to gain insight into epidemiological patterns.”
The paper relies on this without support.
Animal models of DILI are informative for human DILI mechanisms.
“Lorincz et al. (Citation2015) noted that challenge with ferrostatin-1 (specific ferroptosis inhibitor) in primary mouse hepatocytes treated with acetaminophen increased cell viability.”
The paper relies on this without support.
DILI diagnosis requires exclusion of other hepatic disorders.
“Symptoms may mimic other hepatic disorders such as autoimmune hepatitis which emphasizes the need for DILI diagnosis by exclusion.”
The paper relies on this without support.
Between 5% and 20% of a normal population have preexisting liver impairment or abnormal baseline serum enzyme activity levels.
“It is worth noting that between 5% and 20% of a normal population fall into this category.”
The paper relies on this without support.
Higher dosage is a risk factor for DILI development.
“Higher dosage has also been linked as a potential risk factor for DILI development.”
The paper relies on this without support.
The clinical efficacy and safety of anti-viral drugs used in COVID-19 have potential for hepatotoxicity resulting in DILI after repeated dosing.
“The clinical efficacy and safety of these anti-viral drugs have shown potential for hepatotoxicity resulting in DILI after repeated dosing.”
The paper relies on this without support.
Inhibition of CYP3A4 enzyme activity and liver transporter proteins are important factors leading to disruption of drug metabolism and subsequent manifestation of DILI.
“Inhibition of CYP3A4 enzyme activity and liver transporter proteins are suspected as being important factors leading to disruption of drug metabolism and subsequent manifestation of DILI.”
The paper relies on this without support.
Treatment of DILI is aimed at detoxification, scavenging free radicals, anti-oxidation, hepatocyte protection and immune regulation.
“Treatment is aimed at detoxification, scavenging free radicals, anti-oxidation, hepatocyte protection and immune regulation.”
The authors state this as an assumption.
Clinically asymptomatic MASLD might render patients under medication to a higher risk for developing liver injury.
“Assuming that clinically asymptomatic MASLD might render patients under medication to a higher risk for developing liver injury, then this cohort is clearly underrepresented in clinical safety studies.”
The authors state this as an assumption.
Heavy drinkers might be more susceptible to developing acute DILI.
“It is not unreasonable to assume the same argument might be valid for heavy drinkers who might be more susceptible to developing acute DILI.”
The paper relies on this without support.
Treatment for DILI is limited.
“As treatment for DILI is limited, focus has shifted toward prevention.”
The paper relies on this without support.
Most cases of DILI are self-limiting and resolve upon withdrawal of the offending drug.
“Most cases of DILI are self-limiting and resolve upon withdrawal of the offending drug, but treatments for more serious reactions are limited.”
The paper relies on this without support.
There is no standardized clinical guidance for the treatment of DILI as most treatments are nonspecific.
“There is no standardized clinical guidance for the treatment of DILI as most treatments are nonspecific.”
The paper relies on this without support.
Current causality assessment models may be ambiguous, lacking data to comprehensively evidence some of their components.
“Current causality assessment models may be ambiguous, lacking data to comprehensively evidence some of their components.”
The paper relies on this without support.
The lack of specific biomarkers makes distinguishing DILI cases from other hepatic conditions difficult.
“The lack of specific biomarkers makes distinguishing DILI cases from other hepatic conditions difficult.”
The paper relies on this without support.
The diagnosis of DILI relies upon the exclusion of alternative causes.
“This problem is worsened as the diagnosis of DILI relies upon the exclusion of alternative causes.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Molecular mechanisms involved in DILI include mitochondrial dysfunction, increased reactive oxygen species generation, depletion of ATP, increased apoptosis and necrosis, altered bile acid homeostasis/bile duct injuries, and, as a result, cell death by apoptosis or necrosis (Fig. 1). [6–8]”
From Drug-induced liver injury: Diagnosis, management and the role of liver transplantation (2025) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Methods
“If the result is >5 it is considered hepatocellular”
§ Methods
“between 2 and 5 is mixed and >2 is considered cholestatic.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Pages 442-467 | Published online: 02 Oct 2023”
§ References
“NHS. 2023. Accessed November 1 2023.”
Citations
Cites
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Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle
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Research works printed but not linked: 7
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- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. 2012c. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. Carbamazepine. [Updated 2017 Jan 15]. https://www.ncbi.nlm.nih.gov/books/NBK548097/
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Metadata
- Authors
- Allison, R., Guraka, A., Shawa, I. T., Tripathi, G., Moritz, W., & Kermanizadeh, A.
- Affiliations
- University of Derby (GB)
- Nottingham Trent University (GB)
- InSphero AG, Schlieren, Switzerland
- Corresponding author
- Kermanizadeh, Ali
- Venue
- Journal of Toxicology and Environmental Health, Part B
- Publisher
- Informa UK Limited
- Published
- 2023-10-02
- Volume
- 26
- Issue
- 8
- Pages
- 442-467
- ISSN
- 1093-7404 (ISSN-L)
- 1521-6950
- OpenAlex
- W4387296925
- Cited by
- 167
- References
- 145
- Citations by year
- 2026: 56 · 2025: 75 · 2024: 32 · 2023: 2
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Toxicology and Environmental Health Part B (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Animal Free Research UK
- UK Research and Innovation
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- drug-induced liver injury, idiosyncratic drug reactions, hepatotoxicity mechanisms, mitochondrial dysfunction, reactive oxygen species, apoptosis and necrosis, immune-mediated liver injury, hepatocyte injury, cholestatic liver injury, risk factors, COVID-19 pandemic impact, biomarkers, causality assessment, adverse drug reaction reporting
- MeSH terms
- Humans, Liver Diseases, Retrospective Studies, Risk Factors, Chemical and Drug Induced Liver Injury
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