Drug‐induced liver injury in Australia, 2009–2020: the increasing proportion of non‐paracetamol cases linked with herbal and dietary supplements
Open accessAbstract
OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.
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
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?
For sources examining causes of ALI/ALF, Scotland and Australia had the highest number of cases relating to paracetamol at approximately 78% and 63%, respectively.
“For sources examining causes of ALI/ALF, Scotland and Australia had the highest number of cases relating to paracetamol at approximately 78% [204] and 63% [201], respectively.”
From Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease (2023) · cites this paper as [201]
Paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF.
“Overall, paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF [201-208] and 7.3% (range 1.2-29.2%) of drug-induced liver injury (DILI) [209-219] (see Figure 7).”
From Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease (2023) · cites this paper as [201]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Early indicators of prognosis in fulminant hepatic failure
O'Grady, J. G., Alexander, G. J. M., Hayllar, K. M., & Williams, R. (1989) · Gastroenterology · doi:10.1016/0016-5085(89)90081-4 · Cited by 2,085 · see citing works
The model for end-stage liver disease (MELD)
Kamath, P. S., & Kim, R. W. (2007) · Hepatology · doi:10.1002/hep.21563 · Cited by 1,674 · see citing works
Danan, G., & Benichou, C. (1993) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(93)90101-6 · Cited by 1,481 · see citing works
EASL Clinical Practice Guidelines: Drug-induced liver injury
Andrade, R. J., Aithal, G. P., Bjornsson, E. S., Kaplowitz, N., Kullak-Ublick, G. A., Larrey, D. G., & Karlsen, T. H. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.02.014 · Cited by 1,254 · see citing works
Criteria of drug-induced liver disorders
(1990) · Journal of Hepatology · doi:10.1016/0168-8278(90)90124-a · Cited by 1,106 · see citing works
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 · see citing works
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 · see citing works
Liver injury from herbal and dietary supplements
Navarro, V. J., Khan, I. A., Bjornsson, E. S., Seeff, L. B., Serrano, J., & Hoofnagle, J. H. (2016) · Hepatology · doi:10.1002/hep.28813 · Cited by 462 · see citing works
Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network
Navarro, V. J., Barnhart, H., Bonkovsky, H. L., Davern, T., Fontana, R. J., Grant, L., Reddy, R. K., Seeff, L. B., Serrano, J., Sherker, A. H., et al. (2014) · Hepatology · doi:10.1002/hep.27317 · Cited by 418 · see citing works
Katarey, D. R., & Verma, S. (2016) · Clinical Medicine · doi:10.7861/clinmedicine.16-6-s104 · Cited by 339 · see citing works
Robles‐Díaz, M., Lucena, M. I., Kaplowitz, N., Stephens, C. M., Medina‐Cáliz, I., Gonzalez-Jimenez, A., Ulzurrun, E., González, A. F., Fernández, M. C., Romero‐Gómez, M., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.03.050 · Cited by 332 · see citing works
McPhail, M. J. W., Farne, H. A., Senvar, N., Wendon, J. A., & Bernal, W. E. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.10.007 · Cited by 168 · see citing works
Vuppalanchi, R., Liangpunsakul, S., & Chalasani, N. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.01019.x · Cited by 146 · see citing works
Hillman, L., Gottfried, M., Whitsett, M. P., Rakela, J. L., Schilsky, M. L., Lee, W. M., & Ganger, D. R. (2016) · The American Journal of Gastroenterology · doi:10.1038/ajg.2016.114 · Cited by 119 · see citing works
Herbal and Dietary Supplement-Induced Liver Injuries in the Spanish DILI Registry
Medina‐Cáliz, I., García‐Cortés, M., Gonzalez-Jimenez, A., Cabello, M. R., Robles‐Díaz, M., Sanabria‐Cabrera, J., Sanjuán‐Jiménez, R., Ortega‐Alonso, A., García-Muñoz, B., Moreno, I., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.12.051 · Cited by 111 · see citing works
Fatal fulminant hepatic failure induced by a natural therapy containing kava
Gow, P. J., Connelly, N. J., Crowley, P. F., Angus, P., & Hill, R. L. (2003) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2003.tb05286.x · Cited by 94 · see citing works
Herbal and Dietary Supplement–Induced Liver Injury
de Boer, Y. S., & Sherker, A. H. (2016) · Clinics in Liver Disease · doi:10.1016/j.cld.2016.08.010 · Cited by 84 · see citing works
Paracetamol poisoning‐related hospital admissions and deaths in Australia, 2004–2017
Cairns, R., Brown, J. A., Wylie, C. E., Dawson, A. H., Isbister, G. K., & Buckley, N. A. (2019) · Medical Journal of Australia · doi:10.5694/mja2.50296 · Cited by 84 · see citing works
Assessing Supplement Safety — The FDA's Controversial Proposal
Cohen, P. A. (2012) · New England Journal of Medicine · doi:10.1056/nejmp1113325 · Cited by 79 · see citing works
Herbal medicines: challenges in the modern world. Part 1. Australia and New Zealand
Barnes, J., McLachlan, A. J., Sherwin, C. M. T., & Enioutina, E. Y. (2016) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2016.1171712 · Cited by 60 · see citing works
Drug-induced liver injury in older adults
Mitchell, S. J., & Hilmer, S. N. (2010) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098610386281 · Cited by 45 · see citing works
Severe liver injury due to herbal and dietary supplements and the role of liver transplantation
Grewal, P., & Ahmad, J. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i46.6704 · Cited by 30 · see citing works
Drug-induced liver injury in the Australian setting
Sistanizad, M., & Peterson, G. M. (2013) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12039 · Cited by 28 · see citing works
Fulminant liver failure and transplantation after use of dietary supplements
Smith, R. J., Bertilone, C., & Robertson, A. G. (2016) · The Medical Journal of Australia · doi:10.5694/mja15.00816 · Cited by 24 · see citing works
Fatal fulminant hepatic failure induced by a natural therapy containing kava
Gow, P. J., Connelly, N. J., Hill, R. L., et al. (2004) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2004.tb05876.x · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Chidiac, A. S., Buckley, N. A., Noghrehchi, F., & Cairns, R. (2023) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2023.2223959 · Cited by 215 · see citing works
- Authors
- Nash, E., Sabih, A., Chetwood, J., Wood, G., Pandya, K., Yip, T., Majumdar, A., McCaughan, G. W., Strasser, S. I., & Liu, K.
- Affiliations
- Royal Prince Alfred Hospital (AU)
- The University of Sydney (AU)
- Chinese University of Hong Kong (HK)
- Corresponding author
- Liu, Ken
- ORCID
- Venue
- Medical Journal of Australia
- Publisher
- Wiley
- Published
- 2021-07-17
- Volume
- 215
- Issue
- 6
- Pages
- 261-268
- ISSN
- 0025-729X (ISSN-L)
- 1326-5377
- OpenAlex
- W3179773498
- Cited by
- 28
- References
- 25
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 2
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Medical Journal of Australia (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Nephrotoxicity and Medicinal Plants
- Keywords
- drug-induced liver injury, paracetamol, herbal and dietary supplements, antibiotics, transplant-free survival, MELD score, temporal trends, Australia, hospitalization, pharmacovigilance, adverse drug reactions
- MeSH terms
- Acetaminophen, Adult, Anti-Bacterial Agents, Antineoplastic Agents, Antitubercular Agents, Australia, Female, Hospitalization, Humans, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Survival Analysis, Case-Control Studies, Dietary Supplements, Chemical and Drug Induced Liver Injury, End Stage Liver Disease, Antipyretics
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
