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

• Published in: Medical journal of Australia 2021-09, Vol.215 (6), p.261-268
• Main Authors: Nash, Emily, Sabih, Abdul‐Hamid, Chetwood, John, Wood, Georgette, Pandya, Keval, Yip, Terry, Majumdar, Avik, McCaughan, Geoffrey W, Strasser, Simone I, Liu, Ken
• Format: Article
• Language: English
• Subjects: Acetaminophen - toxicity; Adult; Anti-Bacterial Agents - toxicity; Antineoplastic Agents - toxicity; Antipyretics - toxicity; Antitubercular Agents - toxicity; Australia - epidemiology; Case-Control Studies; chemical and drug induced; Chemical and drug induced liver injury; 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; Liver diseases; Liver transplantation; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Survival Analysis
• ISSN: 0025-729X; 1326-5377
• DOI: 10.5694/mja2.51173

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.