Host and Viral Factors Influencing Chronic Hepatitis B Infection Across Three Generations in a Family.

Abstract

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways.