Hepatitis B virus mutations associated with in situ expression of hepatitis B core antigen, viral load and prognosis in chronic hepatitis B patients.
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.
Zhu
Rong
R
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Zhang
Hui-Ping
HP
Yu
Hui
H
Li
Hua
H
Ling
Yu-Qin
YQ
Hu
Xi-Qi
XQ
Zhu
Hong-Guang
HG
D000328:Adult; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology*; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D019562:Viral Load
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens