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

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.

Paracetamol dosing in hospital and on discharge for older people who are frail or have low body weight

“…6 Although paracetamol-induced hepatotoxicity at standard therapeutic doses (up to 4 g/d) is rare, cases have been reported. 4,12,13 Despite a plausible rationale for increased risk of hepatotoxicity in frail and low-weight older people at standard therapeutic doses, and isolated case reports of toxicity with repeated therapeutic dosing, there is no conclusive evidence that low body weight and frailty are independent risk factors for paracetamol-induced hepatotoxicity. 3,5,[8][9][10]14,15 Nevertheless, some clinical guidelines and expert opinions recommend that the dose of paracetamol should be reduced in patients who may be more susceptible to paracetamol-induced liver injury, including older people who are frail or have low body weight (<50 kg).…”

The Role of the NRF2 Pathway in Maintaining and Improving Cognitive Function

“…Curcumin has been reported to display a favorable safety profile although recently a number of cases of acute non-infectious cholestatic hepatitis related to the consumption of curcumin dietary supplements were reported [ 108 , 109 , 110 ]. Curcumin is able to cross the BBB [ 111 , 112 ] without neurotoxicity, even at a high dose [ 113 ].…”

Probiotics: Evolving as a Potential Therapeutic Option against Acetaminophen-Induced Hepatotoxicity

“…In a report, it has been claimed that APAP hepatotoxicity is more prevalent in women as compared to men in the United States [ 37 ]. According to recent reports, hospitalizations for intentional APAP overdose increased by 108% in Australia from 2004 to 2017, and the trend is continuing [ 38 , 39 ]. Similarly, the prevalence of acute APAP toxicity, due to unintentional overdosing, is not uncommon [ 11 ].…”