AUTHOR=Yu Yunfeng , Tong Keke , Hu Gang , Yang Xinyu , Wu Jingyi , Bai Siyang , Yu Rong 

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

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1378311

DOI=10.3389/fmicb.2024.1378311

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Objective</title><p>The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR).</p></sec><sec id="sec2"><title>Methods</title><p>Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran’s <italic>Q</italic> test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis.</p></sec><sec id="sec3"><title>Results</title><p>MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962–0.989; <italic>p</italic> &lt; 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007–1.036; <italic>p</italic> = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002–1.028; <italic>p</italic> = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (<italic>p</italic> &gt; 0.05). Cochran’s <italic>Q</italic> showed no heterogeneity (<italic>p</italic> &gt; 0.05). Leave-one-out sensitivity analysis showed that the results were robust.</p></sec><sec id="sec4"><title>Conclusion</title><p>CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.</p></sec>