Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients

Abstract

Summary Acute liver failure (ALF) or fulminant hepatitis is a rare, yet severe outcome of infection with hepatitis B virus (HBV) that carries a high mortality rate. The occurrence of a life‐threatening condition upon infection with a prevalent virus in individuals without known risk factors is suggestive of pathogen‐specific immune dysregulation. In the absence of established differences in HBV virulence, we hypothesized that ALF upon primary infection with HBV could be due to rare deleterious variants in the human genome. To search for such variants, we performed exome sequencing in 21 previously healthy adults who required liver transplantation upon fulminant HBV infection and 172 controls that were positive for anti‐HBc and anti‐HBs but had no clinical history of jaundice or liver disease. After a series of hypothesis‐driven filtering steps, we searched for putatively pathogenic variants that were significantly associated with case‐control status. We did not find any causal variant or gene, a result that does not support the hypothesis of a shared monogenic basis for human susceptibility to HBV‐related ALF in adults. This study represents a first attempt at deciphering the human genetic contribution to the most severe clinical presentation of acute HBV infection in previously healthy individuals.

Association of single nucleotide polymorphisms in non‑coding RNAs (miRNA‑100 and MALAT1) with susceptibility to hepatitis B virus infection

“…There is high inter-individual variability in the clinical presentation of HBV infection, ranging from self-limited to acute fulminant hepatitis. This can cause chronic liver inflammation leading to cirrhosis and hepatocellular carcinoma (HCC) (2). Despite the presence of effective antiviral therapies and vaccines (3), the mortality rates have increased from 0.8 to 1.4 million from 1990 to 2013 (4).…”