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

Asgari, Samira; Chaturvedi, Nimisha; Scepanovic, Petar; Hammer, Christian; Semmo, Nasser; Giostra, Emiliano; Müllhaupt, Beat; Angus, Peter; Thompson, Alexander J; Moradpour, Darius; Fellay, Jacques (2019). Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients. Journal of viral hepatitis, 26(2), pp. 271-277. Wiley 10.1111/jvh.13019

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Semmo, Nasser

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1352-0504

Publisher:

Wiley

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

19 Dec 2018 08:30

Last Modified:

26 Jan 2019 01:32

Publisher DOI:

10.1111/jvh.13019

PubMed ID:

30315682

Uncontrolled Keywords:

acute liver failure exome sequencing fulminant hepatitis hepatitis B virus

BORIS DOI:

10.7892/boris.122148

URI:

https://boris.unibe.ch/id/eprint/122148

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