Prolonged Intrahepatic Cholestasis After Acute Hepatitis E Infection: A Case Series and Genetic Analysis

Area of Science:

• Hepatology
• Virology
• Human Genetics

Background:

• Hepatitis E virus (HEV) is a major cause of acute viral hepatitis globally.
• While typically self-limiting, HEV can rarely cause prolonged cholestasis.
• Mechanisms for prolonged cholestasis are unclear, but host genetic factors may play a role.

Purpose of the Study:

• Investigate the role of genetic predisposition in HEV-induced prolonged cholestasis.
• Analyze variants in genes crucial for hepatocanalicular transport.
• Explore potential genetic influences on HEV infection outcomes.

Main Methods:

• Retrospective review of medical records from three university centers.
• Identified five immunocompetent patients with prolonged cholestasis post-HEV infection.
• Next-generation sequencing of five genes (ATP8B1, ABCB11, ABCB4, ABCC2, MYO5B) involved in cholestatic liver diseases.
• Compared variant frequencies with asymptomatic HEV-infected blood donors.

Main Results:

• Two patients had potentially pathogenic heterozygous variants: ATP8B1 p.N45T (one patient) and MYO5B p.K429R (one patient).
• Common ABCB11 variants were found in all patients, potentially contributing to cholestasis.
• MYO5B p.K429R was absent in controls; ATP8B1 p.N45T was rare in controls.

Conclusions:

• Host genetic variations may influence the severity of HEV infection, particularly prolonged cholestatic jaundice.
• Specific variants in ATP8B1 and MYO5B could predispose individuals to severe HEV outcomes.
• Further research is needed on the interplay between viral infections and host genetics in liver diseases.