The causal relationship between hepatitis B, immunophenotypes and liver cancer: a Mendelian randomization study

Area of Science:

• Genetics
• Hepatology
• Oncology

Background:

• Hepatocellular carcinoma (HCC) is a major global cancer-related mortality cause.
• Hepatitis B virus (HBV) infection is a primary risk factor for HCC development.
• The direct causal link between HBV and liver cancer requires definitive establishment.

Purpose of the Study:

• To ascertain the causal effect of Hepatitis B virus (HBV) infection on the risk of developing hepatocellular carcinoma (HCC).
• To utilize Mendelian randomization (MR) with genetic variations as instrumental variables for causal inference.

Main Methods:

• Genome-wide association study (GWAS) summary statistics for HCC and HBV were analyzed.
• Mendelian randomization (MR) analysis employed the inverse variance weighted (IVW) method.
• Sensitivity analyses included MR Egger regression and weighted median methods for robustness.

Main Results:

• A significant causal association was found, with HBV infection increasing liver cancer risk (OR=2.233, P<0.001).
• Sensitivity analyses confirmed the causal effect without evidence of horizontal pleiotropy.
• Specific immune phenotypes, including CD25 and HLA DR+ monocytes, were associated with HCC risk.

Conclusions:

• This Mendelian randomization study provides strong evidence for a causal relationship between HBV infection and liver cancer.
• HBV is confirmed as a significant causal factor in the etiology of hepatocellular carcinoma.