Background and Aims
Medications are a major cause of acute liver failure (ALF) in the US, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated healthcare system that approximates a population-based cohort.
Methods
We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) healthcare system between January 1, 2004 and December 31, 2010. We included all KPNC members ≥18 y old with ≥6 months of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF.
Results
Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 (18.8%), antimicrobials in 2 (6.3%), and miscellaneous medications in 6 (18.8%). One patient with acetaminophen-induced ALF died (5.6%; .06 events/1,000,000 person-years) compared to 3 patients with non-acetaminophen induced ALF (21.4%; .18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06–2.35) events and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59–1.63), respectively.
Conclusions
Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.