Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements

Emily Nash; Abdul-Hamid Sabih; John Chetwood; Georgette Wood; Keval Pandya; Terry Yip; Avik Majumdar; Geoffrey W McCaughan; Simone I Strasser; Ken Liu

doi:10.5694/mja2.51173

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements

Med J Aust. 2021 Sep 20;215(6):261-268. doi: 10.5694/mja2.51173. Epub 2021 Jul 17.

Authors

Emily Nash¹, Abdul-Hamid Sabih¹, John Chetwood¹, Georgette Wood², Keval Pandya¹, Terry Yip³, Avik Majumdar^{1

2}, Geoffrey W McCaughan^{1

2}, Simone I Strasser^{1

2}, Ken Liu^{1

2}

Affiliations

¹ AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW.
² Sydney Medical School, University of Sydney, Sydney, NSW.
³ Medical Data Analytic Centre and Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.

PMID: 34272737
DOI: 10.5694/mja2.51173

Abstract

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.

Keywords: Chemical and drug induced liver injury; Liver diseases; Liver transplantation; chemical and drug induced.

MeSH terms

Acetaminophen / toxicity*
Adult
Anti-Bacterial Agents / toxicity
Antineoplastic Agents / toxicity
Antipyretics / toxicity*
Antitubercular Agents / toxicity
Australia / epidemiology
Case-Control Studies
Chemical and Drug Induced Liver Injury / complications
Chemical and Drug Induced Liver Injury / epidemiology*
Chemical and Drug Induced Liver Injury / mortality
Dietary Supplements / toxicity*
End Stage Liver Disease / classification*
End Stage Liver Disease / diagnosis
End Stage Liver Disease / epidemiology
End Stage Liver Disease / mortality
Female
Hospitalization / statistics & numerical data
Hospitalization / trends
Humans
Male
Middle Aged
Predictive Value of Tests
Retrospective Studies
Survival Analysis

Substances

Anti-Bacterial Agents
Antineoplastic Agents
Antipyretics
Antitubercular Agents
Acetaminophen