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

Samira Asgari, Nimisha Chaturvedi, Petar Scepanovic, Christian Hammer, Nasser Semmo, Emiliano Giostra, Beat Müllhaupt, Peter Angus, Alexander J. Thompson, Darius Moradpour, Jacques Fellay

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)271-277
Number of pages7
JournalJournal of Viral Hepatitis
Volume26
Issue number2
DOIs
StatePublished - Feb 2019
Externally publishedYes

Keywords

  • acute liver failure
  • exome sequencing
  • fulminant hepatitis
  • hepatitis B virus

Fingerprint

Dive into the research topics of 'Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients'. Together they form a unique fingerprint.

Cite this