Đột biến gen preS/S của HBV và biến thể NTCP S267F ở bệnh nhân viêm gan B mạn, xơ gan và ung thư biểu mô tế bào gan HBsAg (+)

Hepatocellular carcinoma (HCC) remains a formidable global health challenge, representing a leading cause of cancer-related mortality, particularly in regions with high prevalence of Hepatitis B virus (HBV) infection like Vietnam. The pathogenesis of HBV-associated HCC is notoriously complex, involving intricate interactions between viral factors and host genetic predisposition. Understanding these molecular mechanisms is paramount for developing effective prevention and targeted treatment strategies. This study aims to delineate the associations between specific HBV preS/S gene mutations and the host NTCP S267F variant with the progressive stages of chronic hepatitis B (CHB), liver cirrhosis (LC), and ultimately, hepatocellular carcinoma.

Hepatologists, gastroenterologists, infectious disease specialists, medical geneticists, and researchers focused on viral hepatitis and liver cancer.

This cross-sectional study investigated 429 HBsAg-positive patients, categorized into hepatocellular carcinoma (HCC, n=231), liver cirrhosis (LC, n=96), and chronic hepatitis B (CHB, n=102) cohorts, to determine the interplay of viral and host genetic factors in liver disease progression. Using Sanger sequencing, researchers identified HBV preS/S gene mutations (aa20-174) and the NTCP S267F variant. The findings revealed 28 hotspot preS/S mutations, with their distribution largely consistent across the three patient groups. Significantly, a specific N51M/Y/P/T/D/S/K/Q mutation in HBV genotype B was strongly associated with a 5-fold increased risk of HCC development from chronic liver disease. While the NTCP S267F variant was observed more frequently in the HCC group (16.9%) compared to LC (6.2%) and CHB (5.9%), this difference did not reach statistical significance across groups. Furthermore, no association was established between the NTCP S267F variant and mutations within the NTCP-binding region of HBV. These results collectively underscore the synergistic involvement of both viral preS/S mutations and host genetic factors in the intricate pathogenesis of hepatocellular carcinoma, offering crucial insights for future prognostic markers and therapeutic interventions against HBV-related liver disease.