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Cited by 0Drug-Induced Hepatotoxicity and ProtectionPharmacovigilance and Adverse Drug ReactionsDrug-Induced Adverse Reactions

The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index; none of the 137 sources its claims cite is checked for support yet.

The contemporary epidemiology, causes, and management of drug-induced liver injury

Open access
Swanson, Linea, Fontana, Robert J.·2026·Hepatology Communications
DOI 10.1097/hc9.0000000000001011PMC PMC13671609
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Abstract

Drug-induced liver injury is an important cause of clinically significant liver disease. In Western countries, antibiotics are the leading cause of DILI, with amoxicillin–clavulanate and trimethoprim–sulfamethoxazole most frequently implicated. Herbal and dietary supplements (HDS) are increasingly implicated as a cause of DILI worldwide, including ashwagandha, turmeric, and green tea extract in the United States. Advances in DILI diagnosis include the development of the Revised Electronic Causality Assessment Method (RECAM) instrument and the creation of the LiverTox website with drug and HDS likelihood scores. Newer causes of DILI include kinase inhibitors for cancer and autoimmune conditions, various immunomodulatory agents, and medications to treat liver disease. Immune-mediated liver injury from checkpoint inhibitors (ILICI) typically presents within the first 6 months of treatment with asymptomatic laboratory abnormalities. Treatment of DILI remains primarily supportive by withholding the offending agent and close monitoring, with corticosteroids only showing benefit in highly selected patients. Over 80% of DILI patients will fully recover within 6 months of drug discontinuation with supportive care, but recent outcomes for DILI-related ALF due to HDS have been worsening. Prognostic models can help identify hospitalized DILI patients in need of transplant and others who are at increased risk for 6-month mortality. Whole-exome sequencing to identify new genetic risk factors, development of in vitro diagnostic assays, and further studies of the host adaptive immune response in DILI pathogenesis will hopefully lead to further improvements in DILI diagnosis and treatment.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Drug-induced liver injury is an uncommon but important cause of acute and chronic liver disease, with antibiotics still leading in Western countries while herbal/dietary supplements and newer agents such as immune checkpoint inhibitors and kinase inhibitors are increasingly implicated. Diagnosis relies on exclusion of competing causes plus tools like RECAM and LiverTox, and management remains primarily drug withdrawal and supportive care, with selected use of corticosteroids, N-acetylcysteine, and ursodeoxycholic acid.

Key findings

  • Pooled DILI incidence was 4.9 per 100,000 person-years in a meta-analysis of 14 studies, with prospective population-based rates of 19.1 and 13.9 per 100,000 in Iceland and France, 2 per 100,000 in Delaware and Sweden, and an estimated 23.8 per 100,000 in hospitalized patients in mainland China. In registries, antimicrobials were the leading drug class, amoxicillin–clavulanate was the most frequently implicated individual agent in Western countries, and HDS accounted for 3.4%–16.1% of cases; DILIN HDS cases rose from 7% to 20% between 2004 and 2012, and US ALF cases attributed to HDS rose from 9.7% in 1998–2007 to 22% in 2008–2018.
  • The 2022 RECAM instrument removed non-evidence-based risk factors, anchored hepatotoxicity scoring to LiverTox likelihood scores, and added an optional histology/rechallenge domain; it improved sensitivity for extreme likelihood categories but still had only 62% agreement with expert opinion. LiverTox provides clinical hepatotoxicity data and likelihood scores on over 1200 drugs and 160 HDS products.
  • Newly emphasized causes include immune-mediated liver injury from checkpoint inhibitors (ILICI), with incidence 5%–10% overall and up to 20% in hepatocellular carcinoma, typically presenting within the first 6 months; 70%–80% normalize liver tests after withholding the drug and giving corticosteroids. There are 85 FDA-approved kinase inhibitors, more than half associated with mild reversible AST/ALT elevations and <5% with severe hepatotoxicity with jaundice. Turmeric-associated DILI cases were 80% female, 50% hospitalized, and 1 of 7 patients (11%) died; HLA-B*35:01 was associated with turmeric, green tea extract, and Polygonum multiflorum hepatotoxicity.
  • Over 80% of DILI patients fully recover within 6 months of drug discontinuation, while 4.6%–17.1% develop chronic DILI. In non-acetaminophen ALF with early encephalopathy, intravenous N-acetylcysteine improved transplant-free survival from 27% to 58% but showed no overall survival benefit at 3 weeks; corticosteroids benefit highly selected groups such as ILICI or drug-induced autoimmune hepatitis, not moderate-to-severe idiosyncratic DILI. The DILI-Inpt prognostic score, using 5 variables in 305 inpatients, was superior to MELD and King’s College criteria for predicting 21-day transplant-free survival.

Methods

  • Narrative review synthesizing prospective DILI registries (DILIN, Pro-Euro DILI, Spanish, Latin American, Indian, Japanese), population-based incidence studies, a meta-analysis, clinical trials, case series, and genetic association studies.
  • Main analysis is a qualitative synthesis presented through tables of registry features and outcomes, RECAM domains and interpretation, drug-specific HLA associations, CTCAE grading for checkpoint inhibitor hepatotoxicity, and key clinical pearls.
  • No primary data collection, systematic search strategy, or formal quality appraisal is reported.

Limitations

  • The paper does not state a formal limitations section.
  • Evident from the text: DILI diagnosis remains difficult and relies primarily on expert opinion and clinical judgment; under-reporting is likely due to lack of reliable diagnostic tests and billing codes, and RECAM still agrees with expert opinion only 62% of the time.
  • Evident from the text: many treatment and management conclusions rest on observational studies, case series, and registry data, with a stated lack of randomized controlled trials for ursodeoxycholic acid and most corticosteroid studies lacking contemporary controls.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1097/hc9.0000000000001011

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 137 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    In Singapore, China, and Korea, HDS products have surpassed prescription medications as suspect agents.

    “In Singapore, China, and Korea, HDS products have surpassed prescription medications as suspect agents.7,17,18”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Shen T Liu Y Shang J Xie Q Li J Yan M. Incidence and etiology of drug-induced liver injury in Mainland China. Gastroenterology. 2019; 156: 2230– 2241. 30742832
    • cites [17] Wai CT. Presentation of drug-induced liver injury in Singapore. Singapore Med J. 2006; 47: 116– 120. 16435052
    • cites [18] Suk KT Kim DJ Kim CH Park SH Yoon JH Kim YS. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol. 2012; 107: 1380– 1387. 22733303
  • Premisecitation

    Population-based studies in Delaware and Sweden reported lower rates of DILI at 2 per 100,000 person-years.

    “In comparison, population-based studies in Delaware and Sweden reported lower rates of DILI at 2 per 100,000 person-years.5,6”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Vega M Verma M Beswick D Bey S Hossack J Merriman N. The incidence of drug- and herbal and dietary supplement-induced liver injury: Preliminary findings from gastroenterologist-based surveillance in the population of the state of Delaware. Drug Saf. 2017; 40: 783– 787. PMC5699929 28555362
    • cites [6] De Valle MB Av Klinteberg V Alem N Olsson R Björnsson E. Drug-induced liver injury in a Swedish University hospital out-patient hepatology clinic. Aliment Pharmacol Ther. 2006; 24: 1187– 1195. 17014577
  • Premisecitation

    Retrospective data from mainland China suggest a higher incidence of DILI in hospitalized patients with an estimated annual incidence of 23.8 per 100,000 person-years.

    “Retrospective data from mainland China suggest a higher incidence of DILI in hospitalized patients with an estimated annual incidence of 23.8 per 100,000 person-years. 7”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Shen T Liu Y Shang J Xie Q Li J Yan M. Incidence and etiology of drug-induced liver injury in Mainland China. Gastroenterology. 2019; 156: 2230– 2241. 30742832
  • Premisecitation

    A subset of antibiotics [minocycline, AC, nitrofurantoin, terbinafine, trimethoprim-sulfamethoxazole] had an estimated incidence of 1 DILI case per 1000-5000 prescriptions.

    “Azithromycin had the highest estimated annual incidence of DILI at 1 case per 350 new prescriptions, older anti-epileptic drugs (AEDs) were one DILI case per 350–2500 prescriptions, and a subset of antibiotics [minocycline, AC, nitrofurantoin, terbinafine, trimethoprim–sulfamethoxazole (TMP/SMX)] had an estimated incidence of 1 DILI case per 1000–5000 prescriptions. 20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Chen VL Rockey DC Bjornsson ES Barnhart H Hoofnagle JH. Incidence of idiosyncratic drug-induced liver injury caused by prescription drugs. Drug Saf. 2025; 48: 151– 160. PMC11785493 39317916
  • Premisecitation

    In the DILI registries, the proportion of cases attributed to an HDS product varied from 3.4% to 16.1%.

    “In the DILI registries, the proportion of cases attributed to an HDS product varied from 3.4% to 16.1% (Table 1).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [8] Chalasani N Bonkovsky HL Fontana R Lee W Stolz A Talwalkar J. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology. 2015; 148: 1340– 1352. PMC4446235 25754159
    • cites [9] Björnsson ES Stephens C Atallah E Robles-Diaz M Alvarez-Alvarez I Gerbes A. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023; 43: 115– 126. PMC7614006 35899490
    • cites [10] Stephens C Robles-Diaz M Medina-Caliz I Garcia-Cortes M Ortega-Alonso A Sanabria-Cabrera J. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021; 75: 86– 97. 33539847
    • cites [11] Bessone F Hernandez N Medina-Caliz I García-Cortés M Schinoni MI Mendizabal M. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025; 23: 89– 102. 38992407
    • cites [12] Devarbhavi H Joseph T Sunil Kumar N Rathi C Thomas V Prasad Singh S. The Indian Network of Drug-Induced Liver Injury: Etiology, clinical features, outcome and prognostic markers in 1288 patients. J Clin Exp Hepatol. 2021; 11: 288– 298. PMC8103312 33994711
    • cites [13] Aiso M Takikawa H Tsuji K Kagawa T Watanabe M Tanaka A. Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan. Hepatol Res. 2019; 49: 105– 110. 30565816
  • It may state two separate claims as one. 40
  • Probably not a substantial claim. 15

  • It may state two separate claims as one.

    Premisecitation

    A recent meta-analysis of 14 studies reported the pooled incidence of DILI to be 4.9 per 100,000 person-years, with significant variability among countries.

    “A recent meta-analysis of 14 studies reported the pooled incidence of DILI to be 4.9 per 100,000 person-years, though significant variability was noted among countries. 2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Li M Wang Y Lv TT Liu JM Kong YY Jia JD. Mapping the incidence of drug-induced liver injury: A systematic review and meta-analysis. J Dig Dis. 2023; 24: 332– 339. 37460777

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

    Premisenone given

    After an additional workup excludes competing etiologies, standardized causality assessment instruments can help determine the probability of DILI.

    “After an additional workup excludes competing etiologies, standardized causality assessment instruments can help determine the probability of DILI.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    The RECAM removed non-evidence-based risk factors (age, alcohol, pregnancy), anchored hepatoxicity scoring to LiverTox likelihood scores, and added an optional domain 5 to include liver histology and rechallenge data when available.

    “In addition to creating a computerized interface with detailed user instructions, the RECAM removed non–evidence-based risk factors (age, alcohol, pregnancy), anchored hepatoxicity scoring to LiverTox likelihood scores, and added an optional domain 5 to include liver histology and rechallenge data when available (Table 2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Hayashi PH Lucena MI Fontana RJ Bjornsson ES Aithal GP Barnhart H. A revised electronic version of RUCAM for the diagnosis of drug-induced liver injury. Hepatology. 2022; 76: 18– 31. PMC9233102 35014066

  • 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.

    Premisenone given

    Over the past 20 years, the causes of idiosyncratic DILI in the United States have significantly evolved, with fewer cases attributed to antibiotics, anti-tuberculosis (TB) drugs, and aromatic anticonvulsants and an increasing proportion attributed to herbal and dietary supplements (HDS) and oncological agents.

    “Over the past 20 years, the causes of idiosyncratic DILI in the United States have significantly evolved, with fewer cases attributed to antibiotics, anti-tuberculosis (TB) drugs, and aromatic anticonvulsants and an increasing proportion attributed to herbal and dietary supplements (HDS) and oncological agents.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Premisenone given

    Currently, the diagnosis of DILI relies primarily on expert opinion and clinical judgment after exclusion of more common causes of liver injury with a compelling temporal association between drug exposure and injury onset and improvement following drug cessation.

    “Currently, the diagnosis of DILI relies primarily on expert opinion and clinical judgment after exclusion of more common causes of liver injury with a compelling temporal association between drug exposure and injury onset and improvement following drug cessation.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Premisecitation

    Patients enrolled in prospective DILI registries were 49-59 years of age with a slight female predominance.

    “Patients enrolled in these studies were 49–59 years of age with a slight female predominance.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [8] Chalasani N Bonkovsky HL Fontana R Lee W Stolz A Talwalkar J. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology. 2015; 148: 1340– 1352. PMC4446235 25754159
    • cites [9] Björnsson ES Stephens C Atallah E Robles-Diaz M Alvarez-Alvarez I Gerbes A. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023; 43: 115– 126. PMC7614006 35899490
    • cites [10] Stephens C Robles-Diaz M Medina-Caliz I Garcia-Cortes M Ortega-Alonso A Sanabria-Cabrera J. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021; 75: 86– 97. 33539847
    • cites [11] Bessone F Hernandez N Medina-Caliz I García-Cortés M Schinoni MI Mendizabal M. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025; 23: 89– 102. 38992407
    • cites [12] Devarbhavi H Joseph T Sunil Kumar N Rathi C Thomas V Prasad Singh S. The Indian Network of Drug-Induced Liver Injury: Etiology, clinical features, outcome and prognostic markers in 1288 patients. J Clin Exp Hepatol. 2021; 11: 288– 298. PMC8103312 33994711
    • cites [13] Aiso M Takikawa H Tsuji K Kagawa T Watanabe M Tanaka A. Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan. Hepatol Res. 2019; 49: 105– 110. 30565816

  • It may state two separate claims as one.

    Premisecitation

    Although improved and easier to use than the RUCAM, the RECAM still only had 62% agreement with expert opinion.

    “Although improved and easier to use than the RUCAM, the RECAM still only had 62% agreement with expert opinion. 24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Hayashi PH Lucena MI Fontana RJ Bjornsson ES Aithal GP Barnhart H. A revised electronic version of RUCAM for the diagnosis of drug-induced liver injury. Hepatology. 2022; 76: 18– 31. PMC9233102 35014066

  • 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.

    Premisenone given

    Newer causes of DILI include kinase inhibitors for cancer and autoimmune conditions, various immunomodulatory agents, and medications to treat liver disease.

    “Newer causes of DILI include kinase inhibitors for cancer and autoimmune conditions, various immunomodulatory agents, and medications to treat liver disease.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Nearly 60% of adult Americans reported taking an HDS product in the last 30 days between 2017 and 2018, with the frequency of HDS use greatest in older adults.

    “Nearly 60% of adult Americans reported taking an HDS product in the last 30 days between 2017 and 2018, with the frequency of HDS use greatest in older adults. 14”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Mishra S Stierman B Gahche JJ Potischman N. Dietary Supplement Use Among Adults: United States, 2017–2018. Natl Cent Heal Stat. 2021; 399: 1– 8; NCHS Data. 33663653

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

    Premisenone given

    Recent outcomes for DILI-related acute liver failure (ALF) due to HDS have been worsening.

    “Over 80% of DILI patients will fully recover within 6 months of drug discontinuation with supportive care, but recent outcomes for DILI-related ALF due to HDS have been worsening.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisenone given

    Treatment of DILI remains primarily supportive by withholding the offending agent and close monitoring, with corticosteroids only showing benefit in highly selected patients.

    “Treatment of DILI remains primarily supportive by withholding the offending agent and close monitoring, with corticosteroids only showing benefit in highly selected patients.”
    Quote in the paperNot a substantial claim

  • 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.

    Premisenone given

    Advances in DILI diagnosis include the development of the Revised Electronic Causality Assessment Method (RECAM) instrument and the creation of the LiverTox website with drug and HDS likelihood scores.

    “Advances in DILI diagnosis include the development of the Revised Electronic Causality Assessment Method (RECAM) instrument and the creation of the LiverTox website with drug and HDS likelihood scores.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    The group from Cincinnati reported 123 suspected DILI cases and found that removal of the requirement for HCV-RNA and HEV testing would improve the scoring system compared with expert opinion.

    “The group from Cincinnati reported 123 suspected DILI cases and found that removal of the requirement for HCV-RNA and HEV testing would improve the scoring system compared with expert opinion. 25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Ciricillo J Myer A Yeboah-Korang A Osman A Rahim F Goldfarb DG. Improving the diagnostic accuracy of RECAM in North American patients with suspected idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2025; 120: 1325– 1333. 39422304

  • It may state two separate claims as one.

    Premisenone given

    In Western countries, antibiotics are the leading cause of DILI, with amoxicillin-clavulanate and trimethoprim-sulfamethoxazole most frequently implicated.

    “In Western countries, antibiotics are the leading cause of DILI, with amoxicillin–clavulanate and trimethoprim–sulfamethoxazole most frequently implicated.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    The presence of eosinophils and granulomas was associated with a more favorable prognosis, while hepatic fibrosis and ductular reaction were associated with a poorer prognosis.

    “In addition, the presence of eosinophils and granulomas was associated with a more favorable prognosis, while hepatic fibrosis and ductular reaction were associated with a poorer prognosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Kleiner DE Chalasani NP Lee WM Fontana RJ Bonkovsky HL Watkins PB. Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations. Hepatology. 2014; 59: 661– 670. PMC3946736 24037963

  • Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.

    Premisenone given

    Prognostic models can help identify hospitalized DILI patients in need of transplant and others who are at increased risk for 6-month mortality.

    “Prognostic models can help identify hospitalized DILI patients in need of transplant and others who are at increased risk for 6-month mortality.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    Immune-mediated liver injury from checkpoint inhibitors (ILICI) typically presents within the first 6 months of treatment with asymptomatic laboratory abnormalities.

    “Immune-mediated liver injury from checkpoint inhibitors (ILICI) typically presents within the first 6 months of treatment with asymptomatic laboratory abnormalities.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Among hospitalized patients in Iceland, AC was the most frequent drug associated with DILI (1 per 1300 patients), while TMP/SMX had the highest overall proportional risk at ~1 per 1000 new prescriptions.

    “In addition, among hospitalized patients in Iceland, AC was the most frequent drug associated with DILI (ie, 1 per 1300 patients), while TMP/SMX had the highest overall proportional risk at ~1 per 1000 new prescriptions. 21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Björnsson RA Sigurdsson SS Arnarson DT Logason E Björnsson ES. The frequency of drug-induced liver injury due to antibiotics among hospitalised patients. Drug Saf. 2025; 48: 795– 804. 40072769

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

    Premisenone given

    Herbal and dietary supplements (HDS) are increasingly implicated as a cause of DILI worldwide, including ashwagandha, turmeric, and green tea extract in the United States.

    “Herbal and dietary supplements (HDS) are increasingly implicated as a cause of DILI worldwide, including ashwagandha, turmeric, and green tea extract in the United States.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Similar findings were reported by the Japanese.

    “Similar findings were reported by the Japanese. 26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Tanaka A Tsuji K Komiyama Y Tsuruya K Kakisaka K Tsutsui A. RECAM-J 2023—Validation and development of the Japanese version of RECAM for the diagnosis of drug-induced liver injury. Hepatol Res. 2024; 54: 503– 512. 38642343

  • 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.

    Premisenone given

    Multiple studies have demonstrated drug-specific human leukocyte antigen (HLA) associations with DILI susceptibility, implicating the adaptive immune response in its pathogenesis.

    “Multiple studies have demonstrated drug-specific human leukocyte antigen (HLA) associations with DILI susceptibility, implicating the adaptive immune response in its pathogenesis.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Antimicrobials, including anti-TB drugs, were the most common culprit medications, with amoxicillin/clavulanate being the most frequently implicated individual agent in Western countries.

    “Antimicrobials, including anti-TB drugs, were the most common culprit medications, with amoxicillin/clavulanate (AC) being the most frequently implicated individual agent in Western countries.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [8] Chalasani N Bonkovsky HL Fontana R Lee W Stolz A Talwalkar J. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology. 2015; 148: 1340– 1352. PMC4446235 25754159
    • cites [9] Björnsson ES Stephens C Atallah E Robles-Diaz M Alvarez-Alvarez I Gerbes A. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023; 43: 115– 126. PMC7614006 35899490
    • cites [10] Stephens C Robles-Diaz M Medina-Caliz I Garcia-Cortes M Ortega-Alonso A Sanabria-Cabrera J. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021; 75: 86– 97. 33539847
    • cites [11] Bessone F Hernandez N Medina-Caliz I García-Cortés M Schinoni MI Mendizabal M. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025; 23: 89– 102. 38992407
    • cites [12] Devarbhavi H Joseph T Sunil Kumar N Rathi C Thomas V Prasad Singh S. The Indian Network of Drug-Induced Liver Injury: Etiology, clinical features, outcome and prognostic markers in 1288 patients. J Clin Exp Hepatol. 2021; 11: 288– 298. PMC8103312 33994711
    • cites [13] Aiso M Takikawa H Tsuji K Kagawa T Watanabe M Tanaka A. Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan. Hepatol Res. 2019; 49: 105– 110. 30565816

  • It may state two separate claims as one.

    Premisecitation

    In Latin America, Camellia sinensis, Garcinia cambogia, and Herbalife products accounted for almost half of the HDS cases, while in DILIN, green tea extract, anabolic steroids, and turmeric-containing products were the leading causes.

    “In Latin America, Camellia sinensis, Garcinia cambogia, and Herbalife products accounted for almost half of the HDS cases, while in DILIN, green tea extract, anabolic steroids, and turmeric-containing products were the leading causes.11,19”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Bessone F Hernandez N Medina-Caliz I García-Cortés M Schinoni MI Mendizabal M. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025; 23: 89– 102. 38992407
    • cites [19] Halegoua-DeMarzio D Navarro VJ Davis A Ahmad J Avula B Barnhart H. Investigation of the role of chemical analysis in causality assessment of herbal and dietary supplement-induced liver injury. Drug Saf. 2025; 48: 143– 150. PMC11785658 39354283

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

    Premisenone given

    The R ratio at liver injury onset can guide additional serologic and imaging tests to narrow the differential diagnosis.

    “The R ratio at liver injury onset can guide additional serologic and imaging tests to narrow the differential diagnosis (Figure 1).”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    In a case series of hepatotoxicity attributed to AUD medications, disulfiram was most commonly implicated, with only 1 case attributed to naltrexone despite its widespread and increasing use.

    “In a case series of hepatotoxicity attributed to AUD medications, disulfiram was most commonly implicated, with only 1 case attributed to naltrexone despite its widespread and increasing use. 62”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Gopalakrishna H Ghabril M Gu J Li YJ Fontana RJ Kleiner DE. Drug-induced liver injury due to medications for alcohol use disorder: Results from the DILIN Prospective Study. J Addict Med. 2025; 19: 314– 321. PMC12133418 39651750

  • It may state two separate claims as one.

    Premisecitation

    Recent case series have demonstrated clinically significant liver injury in inflammatory bowel disease (IBD) patients receiving anti-tumor necrosis factor (TNF) α agents, with an over-representation of infliximab.

    “Recent case series have demonstrated clinically significant liver injury in inflammatory bowel disease (IBD) patients receiving anti-tumor necrosis factor (TNF) α agents, with an over-representation of infliximab.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [54] Ghabril M Bonkovsky HL Kum C Davern T Hayashi PH Kleiner DE. Liver injury from tumor necrosis factor-α antagonists: Analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013; 11: 558– 564. PMC3865702 23333219
    • cites [55] Björnsson HK Gudbjornsson B Björnsson ES. Infliximab-induced liver injury: Clinical phenotypes, autoimmunity and the role of corticosteroid treatment. J Hepatol. 2022; 76: 86– 92. 34487751

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

    Premisecitation

    A recent population-based study demonstrated that nearly 15 million Americans are using botanical products for general well-being.

    “A recent population-based study demonstrated that nearly 15 million Americans are using botanical products for general well-being. 57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Likhitsup A Chen VL Fontana RJ. Estimated exposure to 6 potentially hepatotoxic botanicals in US adults. JAMA Netw Open. 2024; 7: 1– 15. PMC11301549 39102266

  • It may state two separate claims as one.

    Premisecitation

    The liver injury was cholestatic or mixed in all of the ashwagandha DILI patients, and most of them had protracted jaundice and pruritus, but no fatalities were reported.

    “The liver injury was cholestatic or mixed in all of the ashwagandha DILI patients, and most of them had protracted jaundice and pruritus, but no fatalities were reported. 58”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Björnsson HK Björnsson ES Avula B Khan IA Jonasson JG Ghabril M. Liver injury due to Ashwagandha. A case series from Iceland and the U.S. Drug-Induced Liver Injury Network. Liver Int. 2020; 40: 825– 289. PMC8041491 31991029

  • It may state two separate claims as one.

    Premisenone given

    Clinically, ILICI tends to be mild, with 70%-80% of patients normalizing their liver tests to pretreatment baseline after withholding the drug and administration of corticosteroids.

    “Clinically, ILICI tends to be mild, with 70%–80% of patients normalizing their liver tests to pretreatment baseline after withholding the drug and administration of corticosteroids.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Although many of these patients required short-term corticosteroids, some were successfully rechallenged with other anti-TNFα inhibitors.

    “Although many of these patients required short-term corticosteroids, some were successfully rechallenged with other anti-TNFα inhibitors.54,55”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [54] Ghabril M Bonkovsky HL Kum C Davern T Hayashi PH Kleiner DE. Liver injury from tumor necrosis factor-α antagonists: Analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013; 11: 558– 564. PMC3865702 23333219
    • cites [55] Björnsson HK Gudbjornsson B Björnsson ES. Infliximab-induced liver injury: Clinical phenotypes, autoimmunity and the role of corticosteroid treatment. J Hepatol. 2022; 76: 86– 92. 34487751

  • It may state two separate claims as one.

    Premisecitation

    HLA-B*35:01 was associated with turmeric hepatotoxicity, as it had been previously associated with green tea extract hepatotoxicity.

    “Interestingly, HLA-B*35:01 was associated with turmeric hepatotoxicity, as it had been previously associated with green tea extract hepatotoxicity. 32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Hoofnagle JH Bonkovsky HL Phillips EJ Li YJ Ahmad J Barnhart H. HLA-B*35:01 and green tea–induced liver injury. Hepatology. 2021; 73: 2484– 2493. PMC8052949 32892374

  • It may state two separate claims as one.

    Premisecitation

    The pattern of liver injury with ILICI is hepatocellular in 40%-50% of patients, with older individuals more likely to present with a mixed or cholestatic profile, and typically occurs in the first 6 months of therapy.

    “The pattern of liver injury with ILICI is hepatocellular in 40%–50% of patients, with older individuals more likely to present with a mixed or cholestatic profile, and typically occurs in the first 6 months of therapy.42,43,46”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [42] Tsung I Dolan R Lao CD Fecher L Riggenbach K Yeboah-Korang A. Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Aliment Pharmacol Ther. 2019; 50: 800– 808. 31309615
    • cites [43] Swanson LA Kassab I Tsung I Schneider BJ Fontana RJ. Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Front Oncol. 2022; 12: 984940. PMC9637844 36353563
    • cites [46] De Martin E Michot JM Papouin B Champiat S Mateus C Lambotte O. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018; 68: 1181– 1190. 29427729

  • It may state two separate claims as one.

    Premisecitation

    A diagnosis of ILICI requires exclusion of alternative etiologies via serological testing along with contrast-enhanced cross-sectional imaging of the liver to exclude hepatic metastases and biliary obstruction.

    “A diagnosis of ILICI requires exclusion of alternative etiologies via serological testing along with contrast-enhanced cross-sectional imaging of the liver to exclude hepatic metastases and biliary obstruction.42,43”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Tsung I Dolan R Lao CD Fecher L Riggenbach K Yeboah-Korang A. Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Aliment Pharmacol Ther. 2019; 50: 800– 808. 31309615
    • cites [43] Swanson LA Kassab I Tsung I Schneider BJ Fontana RJ. Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Front Oncol. 2022; 12: 984940. PMC9637844 36353563

  • It may state two separate claims as one.

    Premisecitation

    The majority of these patients present within 6 months with a severe acute hepatocellular injury and have detectable serum autoantibodies and an autoimmune-like hepatitis on biopsy.

    “The majority of these patients present within 6 months with a severe acute hepatocellular injury and have detectable serum autoantibodies and an autoimmune-like hepatitis on biopsy.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [54] Ghabril M Bonkovsky HL Kum C Davern T Hayashi PH Kleiner DE. Liver injury from tumor necrosis factor-α antagonists: Analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013; 11: 558– 564. PMC3865702 23333219
    • cites [55] Björnsson HK Gudbjornsson B Björnsson ES. Infliximab-induced liver injury: Clinical phenotypes, autoimmunity and the role of corticosteroid treatment. J Hepatol. 2022; 76: 86– 92. 34487751

  • It may state two separate claims as one.

    Interpretationreasoning

    These data suggest that individuals with these polymorphisms may be more susceptible to DILI from multiple drugs and highlight the important role of the adaptive immune response in the development of idiosyncratic DILI through drug-derived antigens triggering antigen-specific T-cell responses in genetically susceptible individuals.

    “These data suggest that individuals with these polymorphisms may be more susceptible to DILI from multiple drugs and highlight the important role of the adaptive immune response in the development of idiosyncratic DILI through drug-derived antigens triggering antigen-specific T-cell responses in genetically susceptible individuals.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    There are currently 85 FDA-approved KIs for cancer, autoimmune, and inflammatory conditions, which most frequently target EGFR, JAK, VEGFR, BCR-Abl, ALK, and cyclin-dependent kinases.

    “There are currently 85 FDA-approved KIs for cancer, autoimmune, and inflammatory conditions, which most frequently target EGFR, JAK, VEGFR, BCR-Abl, ALK, and cyclin-dependent kinases. 51”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Roskoski R. Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update. Pharmacol Res. 2023; 216: 107723. 36403719

  • It may state two separate claims as one.

    Premisecitation

    Kratom, which acts as an opioid receptor agonist, can also cause hepatotoxicity with similar features of mixed or cholestatic injury and a prolonged course with jaundice and synthetic dysfunction.

    “Kratom, which acts as an opioid receptor agonist, can also cause hepatotoxicity with similar features of mixed or cholestatic injury and a prolonged course with jaundice and synthetic dysfunction. 59”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Ahmad J Odin JA Hayashi PH Fontana RJ Conjeevaram H Avula B. Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. Drug Induced Liver Injury Network and a review of the literature. Drug Alcohol Depend. 2021; 218: 108426. PMC8113016 33257199

  • It may state two separate claims as one.

    Premisecitation

    In patients with high-grade ILICI who received initial doses of ≥1.5 mg/kg versus <1.5 mg/kg methylprednisolone equivalents, there was no difference in time to normalization of ALT or development of steroid-refractory disease.

    “In a retrospective analysis of patients with high-grade ILICI who received initial doses of either ≥1.5 mg/kg versus <1.5 mg/kg methylprednisolone equivalents, there was no difference in time to normalization of ALT or development of steroid-refractory disease.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Li M Wong D Vogel AS Sack JS Rahma OE Hodi FS. Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis. Hepatology. 2022; 75: 531– 540. 34709662

  • It may state two separate claims as one.

    Premisecitation

    Patients with hepatocellular carcinoma (HCC) are at the highest risk of ILICI, with an incidence of up to 20%, likely due to their underlying liver disease and higher burden of chronic viral infections.

    “Patients with hepatocellular carcinoma (HCC) are at the highest risk of ILICI, with an incidence of up to 20%, likely due to their underlying liver disease and higher burden of chronic viral infections. 45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Yau T Kang YK Kim TY El-Khoueiry AB Santoro A Sangro B. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The CheckMate 040 randomized clinical trial. JAMA Oncol. 2020; 6: 1– 8. PMC7530824 33001135

  • It may state two separate claims as one.

    Premisecitation

    Immune-mediated liver injury from checkpoint inhibitors (ILICIs) is an increasingly recognized cause of liver injury with an incidence of 5%-10%.

    “Immune-mediated liver injury from checkpoint inhibitors (ILICIs) is an increasingly recognized cause of liver injury with an incidence of 5%–10%.41–43”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [41] Liu Z Zhu Y Xie H Zou Z. Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives. Front Oncol. 2023; 4: 1077468. PMC9868416 36699050
    • cites [42] Tsung I Dolan R Lao CD Fecher L Riggenbach K Yeboah-Korang A. Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Aliment Pharmacol Ther. 2019; 50: 800– 808. 31309615
    • cites [43] Swanson LA Kassab I Tsung I Schneider BJ Fontana RJ. Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Front Oncol. 2022; 12: 984940. PMC9637844 36353563

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

    Premisecitation

    PTPN22 encodes a tyrosine phosphatase that dampens T-cell receptor signaling, and polymorphisms have been associated with several autoimmune diseases.

    “PTPN22 encodes a tyrosine phosphatase that dampens T-cell receptor signaling, and polymorphisms have been associated with several autoimmune diseases. 39”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Stanford S Bottini N. PTPN22: The archetypal non-HLA autoimmunity gene. Nat Rev Rheumatol. 2013; 10: 602– 611. PMC4375551 25003765

  • It may state two separate claims as one.

    Premisecitation

    Despite their widespread use by millions of patients, there have only been a handful of DILI cases attributed to glucagon-like peptide-1 (GLP-1) receptor agonists, although cholecystitis is more frequent compared with placebo-treated patients.

    “Despite their widespread use by millions of patients, there have only been a handful of DILI cases attributed to glucagon-like peptide-1 (GLP-1) receptor agonists, although cholecystitis is more frequent compared with placebo-treated patients.66–68”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [66] Fontana RJ Choi EYK Kaganove J Dodson A. First report of tirzepatide hepatotoxicity with jaundice. Clin Gastroenterol Hepatol. 2024; 22: 2538– 2539. 38964597
    • cites [67] Ma J Mathur K Muldoon JL Ghabril M Chalasani N Vuppalanchi R. Progressive cholestasis and biliary cirrhosis after initiating oral semaglutide: Report from the Drug-Induced Liver Injury Network. ACG Case Reports J. 2022; 9: e00922. PMC9794239 36600793
    • cites [68] Kalsi H Arora SS Essilfie-Quaye K Bassi R Akhavan N Perbtani Y. Semaglutide-induced liver injury. ACG Case Reports J. 2025; 12: e01776. PMC12321452 40761336

  • It may state two separate claims as one.

    Premisecitation

    Most patients with turmeric hepatotoxicity were female (80%) and presented with an acute hepatocellular injury profile, 50% were hospitalized, and 1 patient (11%) died.

    “Most patients with turmeric hepatotoxicity were female (80%) and presented with an acute hepatocellular injury profile, 50% were hospitalized, and 1 patient (11%) died.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Halegoua-DeMarzio D Navarro V Ahmad J Avula B Barnhart H Barritt AS. Liver injury associated with turmeric—A growing problem: Ten cases from the Drug-Induced Liver Injury Network [DILIN]. Am J Med. 2023; 136: 200– 206. PMC9892270 36252717

  • It may state two separate claims as one.

    Premisecitation

    Although severe hepatotoxicity with jaundice from KIs develops in <5%, fulminant hepatitis leading to acute liver failure and an autoimmune phenotype has been reported.

    “Although severe hepatotoxicity with jaundice from KIs develops in <5%, fulminant hepatitis leading to acute liver failure and an autoimmune phenotype has been reported. 52”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Jiang H Jin Y Yan H Xu Z Yang B He Q. Hepatotoxicity of FDA-approved small molecule kinase inhibitors. Expert Opin Drug Saf. 2021; 20: 335– 348. 33356646

  • It may state two separate claims as one.

    Premisecitation

    Clinical trials of obeticholic acid in non-cirrhotic metabolic dysfunction-associated steatotic liver disease (MASLD) failed to demonstrate efficacy and were also associated with a higher rate of liver injury compared with placebo, and the drug was recently withdrawn from the market.

    “Clinical trials of obeticholic acid in non-cirrhotic metabolic dysfunction–associated steatotic liver disease (MASLD) failed to demonstrate efficacy and were also associated with a higher rate of liver injury compared with placebo, and the drug was recently withdrawn from the market. 65”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Alkhouri N LaCerte C Edwards J Poordad F Lawitz E Lee L. Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH. Liver Int. 2024; 44: 966– 978. 38293761

  • It may state two separate claims as one.

    Premisecitation

    HLA polymorphisms shown to be significantly associated with multiple drugs include HLA-A*02:01 for AC and cefazolin DILI and HLA-B*35:01 for multiple HDS products, including green tea extract, turmeric, and Polygonum multiform.

    “HLA polymorphisms shown to be significantly associated with multiple drugs include HLA-A*02:01 for AC and cefazolin DILI and HLA-B*35:01 for multiple HDS products, including green tea extract, turmeric, and Polygonum multiform.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [29] Lucena MI Molokhia M Shen Y Urban TJ Aithal GP Andrade RJ. Susceptibility to amoxicillin–clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011; 141: 338– 347. PMC3129430 21570397
    • cites [30] Vuppalanchi R Li YJ Rockey DC Halegoua-DeMarzio D Fontana RJ Bonkovsky HL. Clinical and genetic associations in cephalosporin-induced liver injury: Insights from the Drug-Induced Liver Injury Network. Aliment Pharmacol Ther. 2025; 62: 1012– 1022. PMC12543336 40685563
    • cites [31] Urban TJ Nicoletti P Chalasani N Serrano J Stolz A Daly AK. Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B*35:02 as a risk factor. J Hepatol. 2017; 67: 137– 144. PMC5634615 28323125
    • cites [32] Hoofnagle JH Bonkovsky HL Phillips EJ Li YJ Ahmad J Barnhart H. HLA-B*35:01 and green tea–induced liver injury. Hepatology. 2021; 73: 2484– 2493. PMC8052949 32892374
    • cites [33] Halegoua-DeMarzio D Navarro V Ahmad J Avula B Barnhart H Barritt AS. Liver injury associated with turmeric—A growing problem: Ten cases from the Drug-Induced Liver Injury Network [DILIN]. Am J Med. 2023; 136: 200– 206. PMC9892270 36252717
    • cites [34] Nicoletti P Aithal GP Bjornsson ES Andrade RJ Sawle A Arrese M. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017; 152: 1078– 1089. PMC5367948 28043905
    • cites [35] Nicoletti P Aithal GP Chamberlain TC Coulthard S Alshabeeb M Grove JI. Drug-induced liver injury due to flucloxacillin: Relevance of multiple human leukocyte antigen alleles. Clin Pharmacol Ther. 2019; 106: 245– 253. 30661239
    • cites [36] Li C Rao T Chen X Zou Z Wei A Tang J. HLA-B*35:01 allele is a potential biomarker for predicting polygonum multiflorum–induced liver injury in humans. Hepatology. 2019; 70: 346– 357. 30985007
    • cites [37] Li YJ Phillips EJ Dellinger A Nicoletti P Schutte R Li D. Human leukocyte antigen B*14:01 and B*35:01 are associated with trimethoprim–sulfamethoxazole induced liver injury. Hepatology. 2021; 73: 268– 281. PMC7544638 32270503

  • It may state two separate claims as one.

    Premisecitation

    Patients with vanishing bile duct syndrome on biopsy have a poorer long-term outcome and frequently remain symptomatic for many months or years.

    “Patients with vanishing bile duct syndrome on biopsy have a poorer long-term outcome and frequently remain symptomatic for many months or years.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Bonkovsky HL Kleiner DE Gu J Odin JA Russo MW Navarro VM. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology. 2017; 65: 1267– 1277. PMC5360519 27981596

  • It may state two separate claims as one.

    Premisecitation

    A systematic review of 11 studies found similar improvement in transplant-free survival with NAC but inconsistent benefit in overall survival.

    “A systematic review of 11 studies found similar improvement in transplant-free survival but inconsistent benefit in overall survival.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Sanabria-Cabrera J Tabbai S Niu H Alvarez-Alvarez I Licata A Björnsson E. N-acetylcysteine for the management of non-acetaminophen drug-induced liver injury in adults: A systematic review. Front Pharmacol. 2022; 13: 876868. PMC9152180 35656297
48 of 48

  • The paper relies on this without support.

    Idiosyncratic drug-induced liver injury is an infrequent but important cause of clinically significant acute and chronic liver injury.

    “Idiosyncratic drug-induced liver injury (DILI) is an infrequent but important cause of clinically significant acute and chronic liver injury.”

  • The paper relies on this without support.

    DILI is uncommon with most marketed drugs, occurring in fewer than 1 in 3000 exposed patients.

    “In addition to being uncommon with most marketed drugs (ie, <1 in 3000 exposed patients), the clinical phenotype and severity of DILI due to a specific agent can vary substantially.”

  • The paper relies on this without support.

    Most cases of idiosyncratic DILI arise within the first 6 months of drug initiation.

    “Host age, gender, and underlying diseases are not reliable risk factors, nor is the dose of the drug administered, but most cases arise within the first 6 months of drug initiation.”

  • The paper relies on this without support.

    Spontaneous survival in DILI-related ALF is 30%.

    “Refer all DILI-related ALF cases to the nearby liver transplant center in light of poor spontaneous survival (30%).”
4 of 4

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.

  • Reported registry age range excludes the Indian registry

    Minor

    The text says patients in the registries were 49-59 years old, but Table 1 reports a median age of 43 years for the Indian registry.

1 of 1

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Galan, 2005, The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center, J Clin Gastroenterol, 39, 64
  2. Mishra, 2021, Dietary Supplement Use Among Adults: United States, 2017–2018, Natl Cent Heal Stat, 399, 1
  3. Wai, 2006, Presentation of drug-induced liver injury in Singapore, Singapore Med J, 47, 116
  4. Liu, 2023, Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives, Front Oncol, 4, 1077468
  5. Bessone, 2025, Ursodeoxycholic acid for the management of drug-induced liver injury: Role of hepatoprotective and anti-cholestatic mechanisms, J Clin Transl Hepatol, 13, 162

Cited by

Still being checked.

Related

Metadata

Authors
Swanson, L., & Fontana, R. J.
Affiliations
University of Michigan (US)
Corresponding author
Fontana, Robert J.
ORCID
Fontana, Robert J.
Venue
Hepatology Communications
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2026-07-20
Volume
10
Issue
8
ISSN
2471-254X (ISSN-L)
DOI
10.1097/hc9.0000000000001011
PMC
PMC13671609
OpenAlex
W7169785460
Cited by
0
References
83
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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 › Pharmacology (medical) › Drug-Induced Adverse Reactions
Keywords
drug-induced liver injury, antibiotic hepatotoxicity, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, herbal and dietary supplements, Withania somnifera, turmeric, green tea extract, immune-mediated liver injury, immune checkpoint inhibitors, kinase inhibitors, immunomodulators, corticosteroid therapy, liver transplantation, acute liver failure, prognostic model, genetic risk factors, exome sequencing, in vitro diagnostic assays
MeSH terms
Anti-Bacterial Agents, Humans, Risk Factors, Chemical and Drug Induced Liver Injury

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