Population-Representative Incidence of Drug-Induced Acute Liver Failure Based on an Analysis of an Integrated Health Care System

Abstract

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.

Plantago major treatment enhanced innate antioxidant activity in experimental acetaminophen toxicity

“…The incidence of drug-induced liver diseases is increasing day by day and unintentional drug toxicity is very common nowadays all over the world. The drug-induced liver diseases attribute more than 50% of acute liver failure [1] . The APAP overdose is associated with high tendency of development of acute liver failure [2] .…”

Drug-Induced Liver Injury: Expanding Our Knowledge by Enlarging Population Analysis With Prospective and Scoring Causality Assessment

“…1,2 In this issue of Gastroenterology, 2 studies provide new details on DILI epidemiology and outcome using different approaches. 3,4 In the first study, 3 the Drug-induced Liver Injury Network (DILIN) presents an updated and subgroup analysis of 889 DILI patients. Their results are in line with an earlier study, 2 confirming a previous study of 461 DILI cases from Spain 1 and a prospective population-based study from Iceland.…”

“…5 The second study used the Kaiser Permanente Northern California database as a surrogate of a wide population sample in order to determine the incidence and outcome of drug-induced acute liver failure (ALF). 4 In both studies, DILI was not confined to synthetic drugs, but also included herbs and herbal dietary supplements, 3,4 which were the second most common causative group (17%) in the DILIN cohort and whose proportion has more than doubled since the initiation of the study in 2004 (7%). 2,4 Indeed, herbs and dietary supplements are a growing cause of liver injury (HILI) worlwide.…”

Acetaminophen (Paracetamol) induced acute liver failure – A social problem in an era of increasing tendency to self-treatment

“…The majority of toxicity cases, including ALF, associated with the ingestion of paracetamol were due to chronic poisoning. This finding constitutes an important warning regarding paracetamol chronic poisoning, and clinicians should have a higher index of clinical suspicion for this entity [16,17,18,19,20].…”