Deoxycholic Acid Promotes Persistent Low-Level Viremia in Chronic Hepatitis B via Enhancing HBV Particle Formation

Area of Science:

• Hepatology
• Virology
• Biochemistry

Background:

• Low-level viremia (LLV) in chronic hepatitis B (CHB) predicts poor treatment outcomes.
• Bile acids (BAs) influence HBV transcription, but their role in LLV is unknown.

Purpose of the Study:

• Investigate the impact of specific bile acids (BAs) on antiviral efficacy in CHB.
• Identify potential therapeutic targets related to BA metabolism for improving CHB treatment.

Main Methods:

• Analyzed 111 CHB patients, profiling serum BAs using mass spectrometry.
• Utilized propensity score matching, correlation, and ROC analyses to link BAs and HBV DNA.
• Conducted in vitro (HepG2.2.15, HepG2-NTCP cells) and in vivo (HBV-transgenic mice) experiments with deoxycholic acid (DCA).

Main Results:

• LLV patients exhibited elevated DCA, LCA, and TUDCA levels, correlating with HBV DNA.
• In vitro, DCA enhanced HBV Dane particle secretion and infection.
• In vivo, hepatic DCA positively correlated with HBV DNA; DCA supplementation reversed antiviral effects.

Conclusions:

• Elevated DCA promotes viral persistence by enhancing Dane particle formation and HBs-HBc interactions, contributing to LLV.
• Modulating BA metabolism presents a potential novel therapeutic strategy for CHB.