INTRODUCTION:Idiosyncratic drug-induced liver injury (DILI) is the second leading cause of acute liver failure (ALF) in the United States. Our study aims were to characterize secular trends in the implicated agents, clinical features, and outcomes of adults with DILI ALF over a 20-year period.METHODS:Among 2,332 patients with ALF enrolled in the ALF Study Group registry, 277 (11.9%) were adjudicated as idiosyncratic DILI ALF (INR ≥ 1.5 and hepatic encephalopathy) through expert opinion. The 155 cases in era 1 (January 20, 1998–January 20, 2008) were compared with the 122 cases in era 2 (January 21, 2008–January 20, 2018).RESULTS:Among 277 cases of DILI ALF, 97 different agents, alone or in combination, were implicated: antimicrobials, n = 118 (43%); herbal/dietary supplements (HDS), n = 42 (15%); central nervous system agents/illicit substances, n = 37 (13%); oncologic/biologic agents, n = 29 (10%); and other, n = 51 (18%). Significant trends over time included (i) an increase in HDS DILI ALF (9.7% vs 22%, P < 0.01) and decrease in antimicrobial-induced DILI ALF (45.8% vs. 38.5%, P = 0.03) and (ii) improved overall transplant-free survival (23.5%–38.7%, P < 0.01) while the number of patients transplanted declined (46.4% vs 33.6%, P < 0.03).DISCUSSION:DILI ALF in North America is evolving, with HDS cases rising and other categories of suspect drugs declining. The reasons for a significant increase in transplant-free survival and reduced need for liver transplantation over time remain unclear but may be due to improvements in critical care, increased NAC utilization, and improved patient prognostication.

Background While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF. Methods From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.5, any degree of hepatic encephalopathy) and 667 with acute liver injury (ALI; INR ≥ 2.0, no hepatic encephalopathy) were enrolled. Anti-HCV testing was done routinely, with confirmatory RT-PCR testing for HCV RNA where necessary. Results A total of 136 patients were anti-HCV-antibody positive, as follows: 56 HCV RNA negative, 65 HCV RNA positive, and 8 with no result nor sera available for testing. Only three subjects with ALI/ALF were determined to represent acute HCV infection. Case 1: 47-year-old female with morbid obesity (BMI 52.4) developed ALF and recovered, experiencing anti-HCV seroconversion. Case 2: 37-year-old female using cocaine presented with ALI and fully recovered. Case 3: 54-year-old female developed ALF requiring transplantation and was anti-HCV negative but viremic prior to transplant experiencing anti-HCV seroconversion thereafter. Among 1636 APAP overdose patients, the 52 with concomitant chronic HCV had higher 3-week mortality than the 1584 without HCV (31% vs 17%, p = 0.01). Conclusions ALI/ALF solely related to acute hepatitis C infection is very rare. Chronic HCV infection, found in at least 65 (2.2%) of ALI/ALF patients studied, contributed to more severe outcomes in APAP ALI/ALF; ClinicalTrials.gov number, NCT000518440. Trial Registration ClinicalTrials.gov number NCT000518440.

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