The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports
Abstract
An important element in assessing causality in drug‐induced liver injury is whether the implicated agent is known to cause hepatotoxicity. We classified drugs into categories based on the number of published reports of convincingly documented, clinically apparent, idiosyncratic liver injury. Drugs described in the website LiverTox (http://livertox.nih.gov) were classified into five categories based on the number of published cases (category A, ≥50; category B, 12‐49; category C, 4‐11; category D, 1‐3; category E, none). Case reports in categories C and D were individually reanalyzed using the Roussel Uclaf Causality Assessment Method. Drugs with fatal cases or with rechallenge were noted. Among 671 individual drugs or closely related agents, 353 (53%) were considered convincingly linked to liver injury in published case reports; 48 (13%) were assigned to category A, 76 (22%) were assigned to category B, 96 (27%) were assigned to category C, and 126 (36%) were assigned to category D. Another 7 (2%) were direct hepatotoxins but only in high doses and placed in a separate category (T). The remaining 318 (47%) drugs had no convincing case report of hepatoxicity in the literature (category E). All except one in category A have been available since 1999, 98% had at least one fatal case and 89% a positive rechallenge. In category B, 54% had a fatal case and 41% a rechallenge. Drugs in categories C and D less frequently had instances of fatal (23% and 7%) or rechallenge cases (26% and 11%). Conclusion : Documentation of hepatoxicity in the medical literature is variable, and many published instances do not stand up to critical review. A standardized system for categorizing drugs for hepatotoxicity potential will help develop objective and reliable, computer‐based instruments for assessing causality in drug‐induced liver injury. (H epatology 2016;63:590–603)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The LiverTox database is known for inclusion of liver injury cases lacking robust CAMs and is therefore disputed.
“Critical is also the data source of used cases, which were partially retrieved from the USA’s National Institutes of Health LiverTox database,67 known for inclusion of liver injury cases lacking robust CAMs and being therefore disputed.69–71”
From Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases (2020) · cites this paper as [70]
Cases were also derived from the LiverTox database, with its published problems in assessing a correct causality in liver injury cases.
“Cases were also derived from the LiverTox database,67 with its published problems in assessing a correct causality in liver injury cases.69–71”
From Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases (2020) · cites this paper as [70]
LiverTox provides comprehensive data on the hepatotoxic risk assessment of over 1000 drugs and 60 HDS.
“‘LiverTox’ is an open access authoritative website developed by Jay Hoofnagle, who was the driving force, with the support of various DILI experts (http://livertox.nih.gov), which provides comprehensive data on the hepatotoxic risk assessment of over 1000 drugs and 60 HDS”
From Methods for causality assessment of idiosyncratic drug‐induced liver injury (2025) · cites this paper as [17]
The likelihood score describes the likelihood of a given drug being associated with DILI, ranging from A to E, based on the number of published cases; it is more accurate for extensively used drugs and less accurate for recently approved drugs and HDS.
“Using this repository, Björnsson & Hoofnagle developed ‘The likelihood score’, that describes the likelihood of a given drug being associated with DILI, ranging from A to E. The score is based on the number of cases published in the literature, so it is more accurate for drugs that have been used extensively over a longer period, and less accurate for more recently approved drugs and HDS that have”
From Methods for causality assessment of idiosyncratic drug‐induced liver injury (2025) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Björnsson, E. S., Bergmann, O. M., Björnsson, H. K., Kvaran, R. B., & Olafsson, S. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.006 · Cited by 865
Flagged first, then by citations
Research works printed but not linked: 20
- 2015, Discrepancies in liver disease labeling in the package inserts of commonly prescribed medications, Gastroenterology, 148, 269, 10.1053/j.gastro.2014.12.007 · DOI
- 1993, Causality assessment of adverse reactions to drugs—I. A novel method based on the conclusions of international consensus meetings: application to drug‐induced liver injuries, J Clin Epidemiol, 46, 1323, 10.1016/0895-4356(93)90101-6 · DOI · Paper page
- 1993, Causality assessment of adverse reactions to drugs‐II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge, J Clin Epidemiol, 46, 1331, 10.1016/0895-4356(93)90102-7 · DOI · Paper page
- 2002, Incidence of drug‐induced hepatic injuries: a French population‐based study, Hepatology, 36, 451, 10.1053/jhep.2002.34857 · DOI
- 2005, Drug‐induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10‐year period, Gastroenterology, 129, 512, 10.1016/j.gastro.2005.05.006 · DOI
- 2009, Phenotypic characterization of idiosyncratic drug‐induced liver injury: the influence of age and gender, Hepatology, 49, 2001, 10.1002/hep.22895 · DOI · Paper page
- 2005, Outcome and prognostic markers in severe drug‐induced liver disease, Hepatology, 42, 481, 10.1002/hep.20800 · DOI · Paper page
- 2005, Fulminant drug‐induced hepatic failure leading to death or liver transplantation in Sweden, Scand J Gastroenterol, 40, 1095, 10.1080/00365520510023846 · DOI · Paper page
- 2006, Drug‐induced liver injury in a Swedish University hospital out‐patient hepatology clinic, Aliment Pharmacol Ther, 24, 1187, 10.1111/j.1365-2036.2006.03117.x · DOI
- 2008, Causes, clinical features, and outcomes from a prospective study of drug‐induced liver injury in the United States, Gastroenterology, 135, 1924, 10.1053/j.gastro.2008.09.011 · DOI
- 2015, Features and outcomes of 889 patients with drug‐induced liver injury: the DILIN Prospective Study, Gastroenterology, 48, 1340
- 2010, Single‐center experience with drug‐induced liver injury from India: causes, outcome, prognosis, and predictors of mortality, Am J Gastroenterol, 105, 2396, 10.1038/ajg.2010.287 · DOI · Paper page
- 2014, Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports, Ann Hepatol, 13, 231, 10.1016/S1665-2681(19)30886-5 · DOI
- 2014, Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges, Drug Saf, 37, S9
- 2009, Drug‐induced liver injury following positive drug rechallenge, Regul Toxicol Pharmacol, 54, 84, 10.1016/j.yrtph.2009.03.003 · DOI
- 2009, Rechallenge in drug‐induced liver injury: the attractive hazard, Expert Opin Drug Saf, 8, 709, 10.1517/14740330903397378 · DOI · Paper page
- 2007, Severe liver toxicity in postexposure prophylaxis for HIV infection with a zidovudine, lamivudine and fosamprenavir/ritonavir regimen, AIDS, 21, 268, 10.1097/QAD.0b013e328011aa35 · DOI
- 1997, Severe hepatitis in three AIDS patients treated with indinavir, Lancet, 349, 924, 10.1016/S0140-6736(05)62700-6 · DOI
- 1998, Indinavir‐associated hepatitis in patients with advanced HIV infection, Int J STD AIDS, 9, 53, 10.1258/0956462981920883 · DOI
- 2011, Causality assessment methods in drug induced liver injury: strengths and weaknesses, J Hepatol, 55, 683, 10.1016/j.jhep.2011.02.007 · DOI · Paper page
Cited by
Sorted by citations
EASL Clinical Practice Guidelines: Drug-induced liver injury
Andrade, R. J., Aithal, G. P., Björnsson, E. S., Kaplowitz, N., Kullak-Ublick, G. A., Larrey, D., & Karlsen, T. H. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.02.014 · Cited by 1,276
Drug-induced liver injury—types and phenotypes
Hoofnagle, J. H., & Björnsson, E. S. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1816149 · Cited by 652
Self-citationChen, M., Suzuki, A., Thakkar, S., Yu, K., Hu, C., & Tong, W. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.02.015 · Cited by 398
AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury
Fontana, R. J., Liou, I., Reuben, A., Suzuki, A., Fiel, M. I., Lee, W., & Navarro, V. (2023) · Hepatology · doi:10.1002/hep.32689 · Cited by 340
LeFort, K. R., Rungratanawanich, W., & Song, B.-J. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-05061-7 · Cited by 202
A revised electronic version of RUCAM for the diagnosis of DILI
Hayashi, P. H., Lucena, M. I., Fontana, R. J., Bjornsson, E. S., Aithal, G. P., Barnhart, H., Gonzalez‐Jimenez, A., Yang, Q., Gu, J., Andrade, R. J., et al. (2022) · Hepatology · doi:10.1002/hep.32327 · Cited by 160
Self-citationSundaram, V., & Björnsson, E. S. (2017) · Hepatology Communications · doi:10.1002/hep4.1088 · Cited by 138
Self-citationTeschke, R., Zhu, Y., & Jing, J. (2020) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2020.00009 · Cited by 41
Methods for causality assessment of idiosyncratic drug‐induced liver injury
García‐Cortés, M., Matilla‐Cabello, G., & Lucena, M. I. (2025) · Liver International · doi:10.1111/liv.16083 · Cited by 15
Metadata
- Authors
- Björnsson, E. S., & Hoofnagle, J. H.
- Affiliations
- The National University Hospital of Iceland,Reykjavik,Iceland
- Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MD
- Venue
- Hepatology
- Published
- 2015-12-21
- Volume
- 63
- Issue
- 2
- Pages
- 590-603
- ISSN
- 0270-9139
- 1527-3350
- Cited by
- 245
- References
- 1
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
