Drug induced liver injury – a 2023 update

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

The underlying mechanisms responsible for DILI are still unknown.

“However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown.”

It may state two separate claims as one.

DILI may be classified as either predictable (intrinsic) or spontaneous (idiosyncratic) with the latter being associated with the most reported clinical presentations.

“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).”

• cites Katarey and Verma Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Chemically inert drugs may form non-covalent interactions with MHC II complexes, altering their binding pocket and encouraging an immune response.

“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).”

• cites Kubes and Jenne Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

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.

“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).”

• cites Gerussi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Investigations conducted in Africa demonstrated that the most common cause of DILI was due to anti-tuberculosis and anti-retroviral drugs utilization.

“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).”

• cites Amadi and Orisakwe Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Riebensahm et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

In acute DILI, reactive metabolites may directly induce misfolded proteins resulting in unfolded protein response (UPR).

“In acute DILI, reactive metabolites may directly induce misfolded proteins resulting in unfolded protein response (UPR).”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Host factors such as age, gender, genetic polymorphisms, lifestyle, and immune status may also contribute to the adverse drug reaction.

“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).”

• cites Villanueva-Paz et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Intrinsic reactions are less common, have a shorter latency period and are often described as being predictable, dose-dependent and reproducible in animal models.

“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).”

• cites Yokoi and Oda Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

DAMPs are released upon hepatocyte damage and initiate further inflammation.

“DAMPs are released upon hepatocyte damage and initiate further inflammation.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Inhibition of BSEPs was a common mechanism underlying drug-induced cholestasis.

“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.”

• cites Villanueva-Paz et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

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.

“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.”

It may state two separate claims as one.

Drug induced hepatic injury may be the result of direct toxicity from xenobiotics or their metabolites or indirectly through an aberrant immune system response.

“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).”

• cites Gerussi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

DILI is a significant concern in preclinical drug development and a leading cause of candidate drug attrition.

“DILI is a significant concern in preclinical drug development and a leading cause of candidate drug attrition (Korver et al. Citation2021).”

• cites Korver et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Frequently used drugs thought to be associated with an immune response include halothane, sulindac, sulfamethoxazole, chlorpromazine, flucloxacillin and amoxicillin-clavulanate.

“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.”

• cites Garcia-Cortes et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Autoantibodies or drug-induced antibodies may combine with bile duct epithelial cells to generate immune complexes that activate complement and damage the bile duct.

“Autoantibodies or drug-induced antibodies may combine with bile duct epithelial cells to generate immune complexes that activate complement and damage the bile duct.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

DILI accounts for approximately 15% of cases of acute liver failure in the United States and Europe.

“DILI accounts for approximately 15% of cases of acute liver failure in the United States and Europe (Reuben et al. Citation2010).”

• cites Reuben et al. Citation2010Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Endoplasmic reticulum stress is reported as a later event within metabolic dysfunction and is thought to occur due to over-accumulation of ROS, imbalance in intracellular Ca2+ levels and activation of the unfolded protein response.

“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).”

• cites Zhang et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Drug lipophilicity is positively associated with DILI risk as this might stimulate hepatocyte absorption, resulting in toxic levels of reactive metabolites.

“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).”

• cites Teschke and Danan Citation2021aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

The elevation in ROS levels activates mitochondrial permeability transition pores which further enhances ROS production and leads to mitochondrial swelling, apoptosis or necrosis.

“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).”

• cites Yan et al. Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Bile salts accumulate due to medication or reactive metabolite blockage of BSEP, which induces inflammation and immune-mediated bile duct damage.

“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).”

• cites Grewal and Ahmad Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Sustained cytotoxic activity may lead to ER-induced stress.

“Similarly, sustained cytotoxic activity may lead to ER-induced stress (Björnsson and Björnsson Citation2022).”

• cites Björnsson and Björnsson Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Pro-inflammatory cytokines are released by CD4+ helper T cells and other immune cells, including macrophages, which further promote inflammation and subsequent hepatic injury.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Pyroptosis is an inflammatory cell death mechanism resulting in activation of caspase which was found to damage hepatic cells and augment organ inflammation.

“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).”

• cites Luan and Ju Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Szabo and Petrasek Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Idiosyncratic reactions are not predictable, not dose-dependent, exhibit variable latency and are not reproducible experimentally in animal models.

“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).”

• cites Fontana et al. Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Hosack, Damry, and Biswas Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Yokoi and Oda Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

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.

“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).”

• cites McGill and Jaeschke Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In direct injury, toxic metabolites might overwhelm hepatic cells leading to an immune response, whereas immune-mediated DILI might occur without accumulation of metabolites as immune mechanisms mistakenly identify drug-altered hepatic cells as foreign.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

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.

“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.”

It may state two separate claims as one.

Hepatocytes are directly injured and undergo apoptosis due to CD8+ cytotoxic T cells activation.

“Hepatocytes are then directly injured and undergo apoptosis due to CD8+ cytotoxic T cells activation.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Direct drug-mediated toxicity, intracellular organelle stress, or hepatocyte membrane damage might activate cell signaling pathways that results in apoptosis or necrosis.

“Direct drug-mediated toxicity, intracellular organelle stress, or hepatocyte membrane damage might activate cell signaling pathways that results in apoptosis or necrosis (Krishna Citation2017).”

• cites Krishna Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

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.

“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.”

It may state two separate claims as one.

Inflammation plays a key role in both acute DILI and immune-mediated DILI.

“Inflammation plays a key role in both types of injury.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

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.

“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).”

• cites Grewal and Ahmad Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

In immune-mediated DILI, elevated levels of pro-inflammatory cytokines might alter ER function.

“In contrast, in immune-mediated DILI the elevated levels of pro-inflammatory cytokines might alter ER function.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The molecular mechanisms involved in T-cell response in DILI are described by the pharmacological interaction p-i model.

“The molecular mechanisms that are involved in T-cell response in DILI are described by the pharmacological interaction p-i model”

• cites Adair, Meng, and Naisbitt Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Gerussi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Pichler Citation2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

The established molecular mechanisms for DILI include mitochondrial dysfunction, increased reactive oxygen species levels, elevated apoptosis and necrosis, and bile duct injuries associated with immune mediated pathways.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Immune-mediated injuries occur when a hypersensitivity reaction provokes an inflammatory response that involves both the innate and adaptive immune systems.

“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).”

• cites Lee and Lawrence Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Approximately half of preclinical drugs with early evidence of hepatotoxicity are terminated prior to achieving market authorization.

“Approximately half of preclinical drugs with early evidence of hepatotoxicity are terminated prior to achieving market authorization (McGill and Jaeschke Citation2019).”

• cites McGill and Jaeschke Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

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.

“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.”

• cites Adair, Meng, and Naisbitt Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Gerussi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Damage-associated molecular patterns are known to bind to toll-like receptors (TLRs) and purinergic receptors expressed by KCs which secrete pro-inflammatory mediators such as IL6, IL18, TNF-α, IFN-Y and Fas ligands which further drive the proliferation of macrophages.

“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).”

• cites Katarey and Verma Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

In countries with a higher usage of a particular compound there tends to be higher incidences of DILI attributed to those specific drugs.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The altered peptide repertoire hypothesis suggests that drugs may induce mistargeting of endogenous peptides leading to HLA autoimmunity.

“The altered peptide repertoire hypothesis suggests that drugs may induce mistargeting of endogenous peptides leading to HLA autoimmunity (Segovia-Zafra et al. Citation2021).”

• cites Segovia-Zafra et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Acute DILI and immune-mediated DILI display distinct underlying causes but share molecular mechanisms that contribute to hepatic injury in both presentations.

“While acute DILI and immune-mediated DILI display distinct underlying causes, there are shared molecular mechanisms that contribute to hepatic injury in both presentations.”

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.

Reactive metabolites might 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.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

BSEP inhibition may lead to bile duct injuries such as obstruction, accumulation of bile salts and interference in sinusoidal uptake.

“BSEP inhibition may lead to bile duct injuries such as obstruction, accumulation of bile salts and interference in sinusoidal uptake.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

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.

“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).”

• cites Eiswerth et al. Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

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.

“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).”

• cites Garcia-Cortes et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

ER stress is a shared mechanism in both acute DILI and immune-mediated DILI, but the specific triggers and pathways involved vary between the two conditions.

“ER stress is another shared mechanism in both presentations, but the specific triggers and pathways involved vary between the two conditions.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Valproate and aspirin were frequent agents associated with DILI in children, whereas amoxicillin-clavulanate was the most frequent causative agent in those over 50.

“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.”

• cites Fisher, Vuppalanchi, and Saxena Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.

Most drugs with a carboxylic acid functional group are metabolized to acyl glucuronides that freely undergo excretion.

“This hypothesis considers that most of these drugs are metabolized to acyl glucuronides that freely undergo excretion (Teschke and Danan Citation2021a).”

• cites Teschke and Danan Citation2021aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Clinical intervention may often be delayed due to a lack of specific symptoms and lab testing.

“Clinical intervention may often be delayed due to a lack of specific symptoms and lab testing.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

HLA-B × 57:01 has been implicated in many DILI cases (OR 80.6); therefore, it is prudent to carry out HLA genetic testing when treating patients with these types of injuries.

“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).”

• cites Ahmad and Odin Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

RUCAM has been frequently utilized since its inception in 1993.

“RUCAM has been frequently utilized since its inception in 1993 (Danan and Benichou Citation1993).”

• cites Danan and Benichou Citation1993Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

There are numerous proposed risk factors for occurrence of iDILI or specific types of injury, including age, biological gender, genetics, preexisting disease state and drug characteristics.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

With DILI symptoms being nonspecific, clinical assessment methods are frequently employed to diagnose cases.

“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).”

• cites Björnsson Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites European Association for the study of the liver 2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In France between 1997 and 2000, anti-microbials (19%) and non-steroidal anti-inflammatory drugs (16%) were associated with the highest incidence of DILI.

“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.”

• cites Sgro et al. Citation2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

Multiple drugs are frequently prescribed concurrently, making isolation of the offending agent increasingly difficult.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Neither old age nor female gender were pre-disposing factors to DILI overall, but rather a determinant for cholestatic injury with male dominance.

“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.”

• cites Lucena et al. Citation2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The MHC consists of more than 200 genes on chromosome 6 and over 1500 alleles of the HLA-B gene were identified.

“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).”

• cites Perwitasari et al. Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Almost all drugs with black box warnings have a daily dosage of >50 mg.

“It is an interesting that almost all drugs with black box warnings have a daily dosage of >50 mg (Vuppalanchi et al. Citation2014).”

• cites Vuppalanchi et al. Citation2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In 2015, DILIN stated 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.

“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).”

• cites Chalasani et al. Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In an Icelandic study of patients with DILI diagnosis from 2010 to 2011 using RUCAM, amoxicillin-clavulanate was the most implicated agent at 22% of DILI patients, followed by diclofenac (6%), azathioprine (4%), infliximab (4%) and nitrofurantoin (4%).

“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).”

• cites Björnsson et al. Citation2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

CRMs generated by CYP450 enzymes produce cellular stress and an association was identified between covalent binding and the risk of iDILI occurrence.

“CRMs generated by CYP450 enzymes produce cellular stress and an association was identified between covalent binding and the risk of iDILI occurrence.”

• cites Jee, Sernoskie, and Uetrecht Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

ULN sometimes varies between different labs, which markedly alters the R ratio calculation.

“However, it is worth mentioning that the ULN sometimes varies between different labs, which markedly alters the calculation.”

It may state two separate claims as one.

Teschke and Danan (2021a) identified 61.1% of drugs implicated in iDILI being metabolized by CYP450 isoforms; among these, almost half (49.6%) were metabolized by CYP3A4 and 5 and almost a quarter (24.6%) were catabolized by CYP2C8 or 9.

“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).”

• cites Teschke and Danan Citation2021aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In an Indian tertiary hospital, 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%).

“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).”

• cites Rathi et al. Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

RUCAM is a diagnostic tool based upon seven clinical observations that provide a framework for diagnosis and evaluation.

“The method is a diagnostic tool based upon seven clinical observations that provide a framework for diagnosis and evaluation (Jee, Sernoskie, and Uetrecht Citation2021).”

• cites Jee, Sernoskie, and Uetrecht Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In the Delaware study, 43% of cases were attributed to herbal dietary supplements and 36% to antibiotics.

“Surprisingly, 43% of cases were attributed to herbal dietary supplements (HDS), while 36% were due to antibiotics (Vega et al. Citation2017).”

• cites Vega et al. Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The Biopharmaceutics Drug Disposition Classification System (BDDCS) evaluates the severity of DILI warning drug labels and is a four-class approach based on water solubility and extent of metabolism.

“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.”

• cites Bocci, Oprea, and Benet Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Females are not at increased risk for DILI but are more likely to progress to acute liver failure, indicating females likely exhibit worsened prognosis once DILI has occurred.

“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.”

• cites Fisher, Vuppalanchi, and Saxena Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

A functional biomarker ideally needs high sensitivity and specificity (>90%) to achieve a high Positive Predictive Value and Negative Predictive Value (70-80%).

“Ideally, a functional biomarker needs exhibit high sensitivity and specificity (>90%) to achieve a high Positive Predictive Value and Negative Predictive Value (70–80%).”

It may state two separate claims as one.

Elevations in ALT, AST, ALP, and total bilirubin are most frequently used for detection but do not reliably correlate with the degree of hepatic impairment and do not show good prognostic value.

“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).”

• cites McGill and Jaeschke Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In that Icelandic study, 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.

“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).”

• cites Björnsson et al. Citation2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Physicians may face issues in discontinuing the offending agent as doing so may worsen the patient's other co-morbidities.

“Physicians may face further issues in discontinuing the offending agent as doing so may worsen the patient’s other co-morbidities.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Chalasani et al. (2015) presented conflicting data regarding female gender being an enhanced risk factor for DILI where a higher prevalence of females (59%) was noted.

“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.”

• cites Chalasani et al. Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Increased lipophilicity of a compound leads to increased permeability and uptake and increased levels of biotransformation and subsequent higher concentrations of toxic metabolites.

“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).”

• cites Teschke and Danan Citation2021aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

RUCAM provides possible causative agent in the case of multiple drug administration, unpredictability of idiosyncratic liver events, and lack of diagnostic biomarkers, inferring that clinical recognition is still troublesome.

“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).”

• cites Hosack, Damry, and Biswas Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Clinical testing is useful for the detection of DILI but is not indicative of prognosis or etiology.

“Clinical testing is useful for the detection of DILI but is not indicative of prognosis or etiology (McGill and Jaeschke Citation2019).”

• cites McGill and Jaeschke Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In a 2016 genome-wide study, the most significant single nucleotide polymorphisms identified were rs114577328 in the major histocompatibility complex region of chromosome 6 and rs72631567 on chromosome 2.

“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).”

• cites Nicoletti et al. Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

Symptoms may mimic other hepatic disorders such as autoimmune hepatitis, emphasizing the need for DILI diagnosis by exclusion.

“Symptoms may mimic other hepatic disorders such as autoimmune hepatitis which emphasizes the need for DILI diagnosis by exclusion.”

• AssumptionRests on an assumption: DILI diagnosis requires exclusion of other hepatic disorders.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In a South African hospital in 2009, the highest risk for DILI was antiretroviral therapy (35%) followed by anti-TB drugs (27%).

“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).”

• cites Schutz et al. Citation2012Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Data suggest that immune-checkpoint inhibitors for HIV treatment are a significant enhanced risk for liver injury.

“Data seem to further suggest that immune-checkpoint inhibitors for HIV treatment are a significant enhanced risk for liver injury (Real et al. Citation2019).”

• cites Real et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In a study from 2001 to 2009, patients aged 60+ accounted for 46% of DILI cases with no cases recorded in the 20-29-year group.

“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).”

• cites Lucena et al. Citation2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

LiverTox is a multilayered and interactive website with evidence-based information on drug, dietary supplements, and herbal-induced liver injury.

“LiverTox (LiverTox Citation2022) is another multilayered and interactive website with evidence-based information on drug, dietary supplements, and herbal-induced liver injury.”

• cites LiverTox Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Younger age was associated with cytolytic damage with a female over-representation.

“Younger age was associated with cytolytic damage with a female over-representation (Lucena et al. Citation2009).”

• cites Lucena et al. Citation2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Recently some issues have been raised regarding the appropriateness of the LiverTox database as a means of predicting iDILI due to concerns with quality of data, lack of evidence-based case studies and absence of standard definitions and categorization of liver injury.

“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).”

• cites Teschke and Danan Citation2021bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

ART/TB drugs and herbal compounds exhibit significantly higher prevalence within the Eastern world, whereas antibiotics, NSAIDs and psychotropic drugs display higher prevalence in the Western world.

“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).”

• cites Low et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In a UK study using the General Practice Research Database from 1994 to 1999, the crude incidence rate of DILI was 2.4 per 100,000 person-years with the strongest drug associations consisting of anti-microbials and NSAIDs.

“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).”

• cites De Abajo et al. Citation2004Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

A common HLA allele present in patients with DILI administered amoxicillin-clavulanate is HLA-DRB1 × 15 and HLA-DRB1 × 06.

“A common HLA allele present in patients with DILI administered amoxicillin-clavulanate is HLA-DRB1 × 15 and HLA-DRB1 × 06.”

• cites Ahmad and Odin Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

There is no official recommendation for scenarios with preexisting liver impairment or abnormal baseline serum enzyme activity levels.

“Further, there is no official recommendation for scenarios with preexisting liver impairment or abnormal baseline serum enzyme activity levels.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Sex hormones are important in regulation of drug metabolism, transport and dimorphism in cellular stress pathways.

“It is believed that sex hormones are important in regulation of drug metabolism, transport and dimorphism in cellular stress pathways (Wang et al. Citation2021).”

• cites Wang et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Flucloxacillin is a frequent cause of DILI and is associated with HLA-B × 57:01.

“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).”

• cites Ahmad and Odin Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

HLA genotyping is now widely accessible, affordable and might assist with diagnosis.

“HLA genotyping is now widely accessible, affordable and might assist with diagnosis.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Teschke and Danan (2020) found that the RUCAM model was used to assess possible cases of idiosyncratic DILI in 81,856 published reports listed on PubMed since 1993.

“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.”

• cites Teschke and Danan Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

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.

“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).”

• cites Bocci, Oprea, and Benet Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In the Swedish study, DILI occurred more often in women and antibiotics were the most frequent agent (30%) followed by diclofenac (22%).

“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%).”

• cites De Valle et al. Citation2006Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The FDA announced support for further clinical exploration of novel biomarkers microRNA-122 and glutamate dehydrogenase.

“Recently, the FDA announced support for further clinical exploration of novel biomarkers microRNA-122 and glutamate dehydrogenase (Andrade et al. Citation2019).”

• cites Andrade et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

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 due to the specific drug in question.

“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).”

• cites Danan and Teschke Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

HLA encodes for components of the MHC which are involved in immune processes that occur during DILI via surface proteins that bind to foreign molecules to elicit an immune response.

“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.”

• cites Ahmad and Odin Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Drugs with a carboxylic acid functional group may be associated with a lower risk of iDILI occurrence.

“On the other hand, drugs with a carboxylic acid functional group may be associated with a lower risk of iDILI occurrence.”

• cites Teschke and Danan Citation2021aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Another study originating in China reported antimicrobial incidence at 32% and glucocorticoids at 24%.

“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).”

• cites Xu et al. Citation2012Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In France, the annual incidence of DILI was 13.9% (±2.4%) per 100,000 inhabitants.

“Sgro et al. (Citation2002) also noted an annual incidence of 13.9% (±2.4%) per 100,000 inhabitants.”

• cites Sgro et al. Citation2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In 2011, the International Serious Adverse Events Consortium set biochemical thresholds at ALT or AST ≥5× ULN and ALP >2 ULN, providing a baseline reference for physicians.

“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).”

• cites Jee, Sernoskie, and Uetrecht Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In a South Korean study of hospitals from 2005 to 2007, the incidence of DILI was 12 per 100,000 inhabitants with frequent causative agents being herbal medications (27.5%).

“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%).”

• cites Suk et al. Citation2012Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In a Swedish study of DILI cases from 1995 to 2005 within a single hospital, 1164 cases were analyzed leading to a DILI diagnosis in 77 cases (6.6%).

“A total of 1164 cases were analyzed leading to a DILI diagnosis in 77 cases (6.6%).”

• cites De Valle et al. Citation2006Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

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).

“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).”

• cites McGill and Jaeschke Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

It has been suggested that glutamate dehydrogenase might be a more specific marker of liver injury as compared to ALT.

“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).”

• cites Clinton et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

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.

“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).”

• cites Chalasani et al. Citation2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In an Icelandic investigation, there was a 3-fold increased risk of DILI in older patients, although this may be attributed to higher prescription rates in the elderly.

“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.”

• cites Björnsson et al. Citation2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In a Delaware (USA) study during 2014, the incidence rate of DILI was 2.7 per 100,000 adult residents.

“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).”

• cites Vega et al. Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper may give no reason why it holds.

There is an increased health risk attributed to toxic compounds exposure including drugs in patients with a metabolically compromised liver.

“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.”

It may state two separate claims as one.

From 1998 to 2009 in the United Kingdom, there was a 43% reduction in paracetamol-related death and a 61% fall in liver transplant following paracetamol overdose.

“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).”

• cites Hawton et al. Citation2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

There is a reported association between the microbiome of the gut and immune mediated DILI, particularly with the use of isoniazid when treating tuberculosis.

“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).”

• cites Liu et al. Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

DILI treatment has remained relatively unchanged for decades.

“DILI treatment has remained relatively unchanged for decades.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In 2023, metabolic dysfunction-associated steatotic liver disease displayed a high prevalence affecting 25% of the global population, amongst whom nearly 30% progressed to metabolic dysfunction-associated steatohepatitis.

“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).”

• cites McPherson et al. Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

At present, there are no approved therapies to manage MASLD.

“At present, there are no approved therapies to manage MASLD.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In severe cases, high dose use of tocilizumab, an IL-8 inhibitor, is utilized to manage the cytokine storm in COVID-19 patients.

“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).”

• cites Muhović et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Vitiello et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Most cases of ALF in the Western world are produced by intrinsic DILI (paracetamol).

“Most cases of ALF in the Western world are produced by intrinsic DILI (paracetamol) (Chan and Benet Citation2017).”

• cites Chan and Benet Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The organs implicated most commonly in SJS are the liver and skin with severe cutaneous adverse reactions.

“The organs implicated most commonly in SJS are the liver and skin with severe cutaneous adverse reactions (Ortega-Alonso et al. Citation2016).”

• cites Ortega-Alonso et al. Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

Hepatoprotective medications including N-acetylcysteine and L-carnitine may be used as an antidote, but these are only indicated for intrinsic DILI.

“Hepatoprotective medications including N-acetylcysteine and L-carnitine may be used as an antidote, but these are only indicated for intrinsic DILI.”

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.

Treatment 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.”

• AssumptionRests on an assumption: Treatment of DILI is aimed at detoxification, scavenging free radicals, anti-oxidation, hepatocyte protection and immune regulation.

It may state two separate claims as one.

A shortage of animal models exists that accurately capture iDILI, although promising candidates exist such as the inflammagen model or the Uetrecht-Pohl model.

“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).”

• cites Segovia-Zafra et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Gerussi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Similar observations were found when anti-viral drugs were applied prophylactically, leading to subsequent liver damage.

“Similar observations were found when anti-viral drugs were applied prophylactically, leading to subsequent liver damage.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

It is estimated that 2 out of every 3 adults in the UK exhibit early stages of MASLD.

“It is now estimated that 2 out of every 3 adults in the UK exhibit early stages of MASLD.”

• cites British Liver Trust Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Immune mediated DILI may benefit from a course of corticosteroids.

“Immune mediated DILI may benefit from a course of corticosteroids.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Numerous investigations noted a link between DILI and polymorphisms of certain HLA genotypes as well as CYP450s.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Recent clinical practice guidelines agree that liver transplantation is still the primary resolution for severe ALF.

“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).”

• cites Devarbhavi et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Andrade et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

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 infects hepatocytes directly via the angiotensin-converting enzyme 2 receptor.

“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.”

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.

The classification of injury needs to be determined as this dictates the treatment plan to follow.

“The classification of injury needs to be determined as this dictates the treatment plan to follow.”

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.

Prompt identification and discontinuation of the offending agent is crucial in early DILI management.

“The prompt identification and discontinuation of the offending agent is crucial in early DILI management.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

SJS is associated with immune-mediated DILI and patients with both SJS and DILI concurrently exhibit a higher risk of morbidity.

“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).”

• cites Andrade et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

In a systematic review of 305 trials, a third were at high risk of bias, most frequently because the clinical population used was not appropriate for the trial examined.

“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.”

• cites He, Morales, and Gutherie Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Xenobiotic-induced adverse effects in the liver are aggravated in the diseased organ.

“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).”

• cites Allard et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Kermanizadeh et al. Citation2017, Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Lammert et al. Citation2019Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Liver injury in mild cases of COVID-19 is usually reversible.

“Liver injury in mild cases of COVID-19 is usually reversible.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

A frequently utilized treatment for cholestatic injury is ursodeoxycholic acid, a naturally occurring hydrophilic bile acid that decreases cholesterol saturation index of bile.

“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).”

• cites Li et al. Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Robles-Diaz et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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.

iDILI is one of the more challenging forms of liver disease, both in terms of diagnosis and management.

“iDILI is one of the more challenging forms of liver disease, both in terms of diagnosis and management.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

96% of adults with MASLD in the United States were unaware that they were suffering from liver disease.

“Importantly, 96% of adults with MASLD in the United States were unaware that these individuals were suffering from liver disease (Alqahtani et al. Citation2021).”

• cites Alqahtani et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

In more severe injuries, a liver biopsy may be required to determine injury type and prognosis.

“In more severe injuries, a liver biopsy may be required to determine injury type and prognosis.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Exposure to xenobiotics might aggravate preexisting liver conditions, related to the growing obesity pandemic, western diet and sedentary lifestyle.

“The exposure to xenobiotics might aggravate preexisting liver conditions, related to the growing obesity pandemic, western diet and sedentary lifestyle.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In one study, iDILI had a 3-week transplant-free survival rate of 27%.

“In one study, iDILI showed a 3-week transplant-free survival rate of just 27% (Ostapowicz et al. Citation2002).”

• cites Ostapowicz et al. Citation2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Biochemical tests may aid diagnosis but are not reliably indicative of severity or prognosis.

“Biochemical tests may aid diagnosis but are not reliably indicative of severity or prognosis (Rathi et al. Citation2017).”

• cites Rathi et al. Citation2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

This is a particular issue in the treatment of TB where no alternative therapies are available.

“This is a particular issue in the treatment of TB where no alternative therapies are available.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Liver support devices such as hemodialysis and MARS might replicate the detoxifying function of the liver and stabilize the patient while awaiting transplant.

“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).”

• cites Adam et al. Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

The most common experimental animal models (particularly mice) express homologs of the major human CYP450s, but not all those homologs possess the same substrate specificity, leading to overall poor human response predictivity.

“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.”

• cites Turpeinen et al. Citation2007Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Approximately 20% of DILI patients develop chronic liver disease.

“Approximately 20% of DILI patients develop chronic liver disease (Wang et al. Citation2021)”

• cites Wang et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper may give no reason why it holds.

Patients with clinically asymptomatic MASLD are clearly underrepresented in clinical safety studies.

“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.”

• AssumptionThe authors state this as an assumption: Clinically asymptomatic MASLD might render patients under medication to a higher risk for developing liver injury.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Inhibition of CYP3A4 enzyme activity and liver transporter proteins are suspected as 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.”

• AssumptionRests 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.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

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 over £10 billion, accounting for 5% of the national health service budget.

“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).”

• cites NHS Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

DILI-related mortality is 5-10% in large cohort studies.

“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.”

• cites Björnsson Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Activated charcoal may provide therapeutic benefits, but its administration is restricted to within 3-4 hr since consumption.

“Activated charcoal may provide therapeutic benefits, but its administration is restricted to within 3–4 hr since consumption (Hosack, Damry, and Biswas Citation2023).”

• cites Hosack, Damry, and Biswas Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Metabolic liver diseases and exposure to xenobiotics might trigger similar cellular stress responses, with the capability to stimulate and accelerate further disease progression.

“Metabolic liver diseases and exposure to xenobiotics might trigger similar cellular stress responses, with the capability to stimulate and accelerate further disease progression.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A rare complication occurs when Stevens-Johnson Syndrome occurs concurrently with DILI.

“A rare complication occurs when Stevens-Johnson Syndrome (SJS) occurs concurrently with DILI.”

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.

Female gender and increased age are not necessarily risk factors for DILI overall, but these demographics are more likely to lead to certain types of injury and greater risk of mortality.

“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.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Mortality rates for liver disease have increased 400% since 1970, and in individuals aged younger than 65 years, mortality frequencies have risen almost 500%.

“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).”

• cites British Liver Trust Citation2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In this scenario, re-challenge strategies may be implemented with the aim of desensitizing patient reaction.

“In this scenario, re-challenge strategies may be implemented with the aim of desensitizing patient reaction (Stine and Lewis Citation2016).”

• cites Stine and Lewis Citation2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Severe COVID-19 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 hepatocytes to reduce liver damage.

“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.”

It may state two separate claims as one.

Direct infection of hepatocytes by SARS-CoV-2 results in liver injury, inflammation, cellular damage, treatment-related DILI and immune-mediated injury.

“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).”

• cites Clinton et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Marjot et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites McGrowder et al. Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

Patients fighting an active COVID-19 infection may be relatively immunodeficient; however, when treated with an array of drugs, the consequence is a greater risk of developing immune-mediated DILI.

“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).”

• cites Bonaventura et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Hui et al. Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Lu, Stratton, and Tang Citation2020Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Proactive measures may be taken for recent ingestion such as in the case of paracetamol overdose.

“Proactive measures may be taken for recent ingestion such as in the case of paracetamol overdose.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Immune-checkpoint inhibitor 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.

“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).”

• cites Björnsson Citation2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Another frequently employed pharmacotherapy is bicyclol, an inflammatory cytokine inhibitor that suppresses activity of various necrosis factors and interleukins.

“Another frequently employed pharmacotherapy is bicyclol, an inflammatory cytokine inhibitor that suppresses activity of various necrosis factors and interleukins (Adam et al. Citation2018).”

• cites Adam et al. Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Diagnosis is made further difficult as DILI follows diagnosis by exclusion.

“Diagnosis is made further difficult as DILI follows diagnosis by exclusion.”

• AssumptionRests on an assumption: DILI diagnosis requires exclusion of other hepatic disorders.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

A significant issue in treating DILI is that the therapeutic effect of the offending agent is lost upon the de-challenge.

“Unfortunately, a significant issue in treating DILI is that the therapeutic effect of the offending agent is lost upon the de-challenge.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In a recent investigation using liver biopsies from COVID-19 patients, microvesicular steatosis, patchy necrosis and infiltration of lymphocytes were shown.

“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.”

• cites Saha, Vij, and Rawat Citation2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The 5-year post-transplant survival rate in DILI-ALF patients is between 70% and 80%.

“Studies indicate a 5-year post-transplant survival rate between 70% and 80% in DILI-ALF patients (Adam et al. Citation2018).”

• cites Adam et al. Citation2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.