The relationship between HBV-associated histopathological indexes, X gene mutations and prognosis in patients with chronic hepatitis B virus infection
Objective To identify the relationship between HBV-associated histopathological indexes, X gene mutations and prognosis in patients with chronic hepatitis B. Methods Patients with liver biopsy samples in 1986—1994 were followed up. All of the 83 cases were divided into three groups: Carcinogenesis, Cirrhosis, and Non-cirrhosis. The rest 20 HBV-related hepatocellular carcinoma cases were also studied. Two-step immunohisto- chemical staining showed the expression of HBsAg, HBcAg, HBeAg and HBx protein in situ. HBV DNA levels in liver were determined by fluorescence quantitative real-time PCR. nt1583-1793 in HBV X gene was amplified by PCR. Products were purified from agarose for sequence analysis in double directions. Results Among the four HBV antigens, the expression of HBsAg was the highest, while HBeAg was the lowest. Missense mutations were found in nt1632-1636(AA 87/88), 1719(AA 116), 1725-1730(AA 118/119), 1752(AA127), 1762 and 1764 (AA 130/131). Statistic analysis showed that grading (P=0.001) and staging (P=0.000) of Scheuer scores were higher in Cirrhosis than those in Non-cirrhosis, as well as the expression of HBeAg in liver (P=0.008). The percentage of nt1762/1764 mutation in Carcinogenesis was significantly higher than that in Non-carcinogenesis (P=0.011). The percentage of wild type of nt1725-1730 was obviously higher in carcinoma cases than that in chronic hepatitis cases (P=0.024), while the percentage of nt1762/1764 mutations did so (P=0.001). Con- clusion Scheuer scores and the expression of HBeAg in liver closely correlate with cirrhosis in patients with chronic hepatitis B. The mutation at nt1762/1764 obviously increases the risk for hepatocarcinogenesis.