Hepatitis B virus mutations associated with in situ expression of hepatitis B core antigen, viral load and prognosis in chronic hepatitis B patients

• Published in: Pathology, research and practice research and practice, 2008-01, Vol.204 (10), p.731-742
• Main Authors: Zhu, Rong, Zhang, Hui-Ping, Yu, Hui, Li, Hua, Ling, Yu-Qin, Hu, Xi-Qi, Zhu, Hong-Guang
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Antigen; Carcinoma, Hepatocellular - virology; DNA Mutational Analysis; DNA, Viral - analysis; Female; Hepatitis B Core Antigens - analysis; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - diagnosis; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - immunology; Humans; Immunohistochemistry; Liver - virology; Liver Cirrhosis - virology; Liver Neoplasms - virology; Male; Middle Aged; Molecular Sequence Data; Mutation; Polymerase Chain Reaction - methods; Prognosis; Quantification; Retrospective Studies; Viral Load
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2008.05.001

In this retrospective study, we investigated the prevalence and significance of mutations in part of the hepatitis B virus (HBV) x gene, and tried to clarify their relationship with clinicopathological or histopathological characteristics and prognosis in patients with chronic hepatitis B (CHB). A total of 83 consecutive CHB patients (1986–1994) were chosen for the present study. Sequence analysis was performed using polymerase chain reaction (PCR) and the direct sequencing method. The histological activity index was described using Scheuer scores. Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real-time PCR. For the prognostic study, all the patients were followed up using clinical and laboratory data. Mutation at nt1726–1730 correlated significantly with decreased expression of HBcAg in situ ( P=0.006) and with lower HBV DNA levels in the liver ( P=0.004). In particular, the CTGAC mutation showed the strongest decrease of the viral load ( P=0.007). By contrast, nt1762/1764 mutation correlated with increased HBcAg ( P=0.005) and higher HBV DNA levels ( P=0.006). The mutants with the wild-type of nt1726–1730 or nt1762/1764 mutation were more prevalent in hepatocellular carcinoma (HCC) patients than in CHB patients. Although the mutations did not correlate with cirrhosis, the frequency of nt1762/1764 mutation in patients with hepatocarcinogenesis was significantly higher than in those without hepatocarcinogenesis ( P=0.011). Mutations at nt1726–1730 and nt1762/1764 are associated with in situ expression of HBcAg and viral load. Higher HBV DNA levels in the liver may be associated with hepatocarcinogenesis. Mutation at nt1762/1764 remarkably increases the risk of hepatocarcinogenesis.