Abstract:

【Abstract】 Objective  To understand the correlation of the genotype of hepatitis B virus(HBV), mutation loci of 1762/1764 and 1896, and HBV transactivator protein X with hepatocellular carcinoma(HCC) for theoretical evidences in early diagnosis and therapy of this entity. Methods  HBV genotypes and their mutation loci were tested by nucleic acid amplification in 159 blood samples obtained from asymptomatic chronic HBV carriers, patients of chronic Hepatitis B, hepatitis B induced cirrhosis and HBV-associated HCC, and sequenced by the auto genotype analyzer and measured with quantitative method. Expression of X protein in the liver tissues from the aforementioned 4 groups were detected by immunohistochemistry staining, and the results were estimated by semi-quantitative integration. Results  1) In the 159 cases infected with chronic HBV, 56 were associated with genotype B(35.2％, 56/159) and 103 with genotype C (64.8％, 103/159). Genotype C in groups of asymptomatic chronic hepatitis B virus carrier(ASC), patients of chronic hepatitis B(CHB), patients with liver cirrhosis(LC) and HCC accounted for. The difference was significant(χ2 =8.462, P =0.037); 2)Mutations of basal core promoter(BCP)were 44.0%(11/25), 63.2%(36/57), 85.7%(36/46) and 64.5%(20/31), respectively for the four groups of HBV patients with genotype C, and cases with precore(PC) mutation were 45.5%(5/11), 66.7%(24/36), 77.8%(28/36) and 70.0%(14/20), respectively. Cases with two mutations were over those with genotype B, and the difference was significant except for ASC group(P <0.05); 3) Protein X expression was the strongest in group LC, with a positive rate of 71.7%, and came next by group HCC(71.0%), CHB(59.6%) and ASC(52.0%). The difference was significant among groups(P<0.05); 4)Positive rate of X protein expression in chronic HBV infectors with genotype C in group ASC, CHB, LC and HCC was 81.8%(9/11), 72.2%(26/36), 86.1%(31/36) and 85.0%(17/20), and was higher than that in genotype B[28.6%(4/14), 38.1%(8/21), 20.0%(2/10) and 45.5%(5/11), respectively],with statistical difference(P <0.05).  The proportion of HBV infectors with positive BCP mutation and positive X protein expression in the four groups was 61.5%, 73.5%, 69.7% and 81.8%, and the proportion was higher than that in HBV infectors with negative BCP mutation. Positive PC mutation was 46.2%, 67.6%, 78.8% and 63.6%, which was higher than the proportion in HBV infectors with negative PC mutation except for group ASC, yet the difference was not significant. Conclusion  HBV genotype C, mutation loci of 1762/1764 and 1896 and X protein are correlated with each other, suggesting that they are involved in the pathogenesis and development of HCC.   

Key words: Chronic HBV infectors, Hepatitis B virus, Genotype, HBV mutation, X protein, Hepatocellular carcinoma