Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study

Area of Science:

• Genetics
• Hepatology
• Epidemiology

Background:

• The relationship between hepatitis B virus (HBV) infection and type 2 diabetes (T2D) risk is debated.
• Understanding this association is crucial for managing both conditions.

Purpose of the Study:

• To investigate the causal link between HBV infection and T2D using Mendelian randomization (MR).
• To clarify the role of chronic hepatitis B (CHB), liver fibrosis, and liver cirrhosis in T2D development.

Main Methods:

• Utilized Mendelian randomization (MR) analysis with genetic data from large biobanks (BioBank Japan, EBI, FinnGen).
• Employed inverse variance weighted (IVW) as the primary MR method.
• Assessed pleiotropy and heterogeneity using MR-Egger intercept and Cochran's Q test, with leave-one-out analysis for robustness.

Main Results:

• Chronic hepatitis B (CHB) showed a significant inverse association with T2D risk (OR, 0.975; p < 0.001).
• Liver cirrhosis and liver fibrosis were associated with increased T2D susceptibility (ORs > 1.015; p < 0.020).
• Sensitivity analyses confirmed the robustness of findings and absence of significant pleiotropy or heterogeneity.

Conclusions:

• Chronic hepatitis B (CHB) may exert a protective effect against type 2 diabetes (T2D).
• This protective effect is contingent on viral load and disease stage, diminishing with reduced viral activity.
• Progression to liver fibrosis and cirrhosis transforms HBV's impact, increasing T2D risk.