Role of Hepatitis C Infection in Acute Liver Injury/Acute Liver Failure in North America

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00518440.

Keywords: Fulminant hepatic failure; Liver transplantation; Viral hepatitis.

Conflict of interest statement

WML serves as a consultant for Affibody, Genentech, Forma, Karuna, SeaGen, Cortexyme, Pfizer, and Alnylam. He receives research funding to conduct clinical trials from Merck, BMS, Intercept, Novo Nordisk, Eiger, and Alexion. RJF receives research support from AbbVie, Gilead, and Bristol Myers Squibb and has consulted for Sanofi. RTS receives funding from IL and Exalenz. AR, JR, GC, BMM, and GL have no financial disclosures to report. All authors certify that they have no non-financial interests (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Fig. 1

ALF and ALI cases stratified by HCV status; 56 patients were anti-HCV-antibody positive and HCV RNA negative consistent with prior resolved infection or false-positive test result; 66 patients were anti-HCV-antibody positive and HCV RNA positive, consistent with current HCV infection; 8 patients were anti-HCV-antibody positive, but HCV RNA testing could not be obtained

Fig. 2

Explanted Liver from Case 3 (H&E stain). A (low power) Lobules (short arrows) show a significant panlobular inflammatory infiltrate with lobular architectural disarray and prominent hepatocyte drop-out. A portal tract on the right (long arrows) reveals an inflammatory infiltrate with interface activity. No bile duct injury is seen. There is no evidence of cirrhosis. B (high power) The lobular inflammatory infiltrate (long arrows) consists predominantly of lymphocytes with plasma cells. Cholestasis (short arrow) is also noted