Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients

Abstract

The aim of the study was to investigate the prevalence of mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and their association with hepatocellular carcinoma. A total of 341 untreated older HBV patients were divided into three groups: chronic hepatitis B (CHB, 185), cirrhotic hepatocellular carcinoma (LC-HCC, 113) and non-cirrhotic hepatocellular carcinoma (non-LC-HCC, 43). HBV BCP and PreC mutations and genotypes were determined by direct sequencing. Using univariate analysis, age (≥ 45 years), single mutations including A1896 and A1899 and multiple mutations T1762/A1764 + A1896, T1762/A1764 + A1899 and T1762/A1764 + A1896 + A1899 were more frequently detected in LC-HCC and non-LC-HCC patients than in CHB patients. BCP T1762/A1764 mutations were highly detected in LC-HCC patients than in CHB patients. Multivariate logistic regression analysis (adjusted for age and gender) revealed that among HBeAg-positive patients, BCP T1762/A1764 mutations (OR, 5.975; P = 0.05), PreC A1899 mutation (OR, 4.180; P = 0.013) and multiple mutations T1762/A1764 + A1899 (OR, 6.408; P = 0.006) were independently associated with the development of LC-HCC; PreC A1899 mutation (OR, 7.347; P = 0.034) was also independently associated with the development of non-LC-HCC. On the other hand, among HBeAg-negative patients, PreC A1896 mutation (OR, 5.176; P = 0.002) and multiple mutations T1762/A1764 + A1896 (OR, 4.149; P = 0.007) were independently associated with the development of non-LC-HCC. These results indicated that older age (≥ 45 years) was associated with LC-HCC and non-LC-HCC development. BCP T1762/A1764 mutations and PreC A1899 mutation were associated with the LC-HCC development in HBeAg-positive patients. PreC A1896 mutation was associated with the non-LC-HCC development in HBeAg-negative patients.

The association between hepatitis B mutants and hepatocellular carcinoma

“…[2,46] The results support the conclusion that each of these mutations (A1762T, G1764A, and A1762T/G1764A) plays a significant role in the progression of chronic HBV infection to HCC. [38,43,47,48] The risk of HCC associated with the double mutation A1762T/G1764A was similar to those described in previous meta-analyses. [5,17] The data show a similar risk of HCC associated with A1762T, G1764A, and A1762T/G1764A with OR of 3.96, 3.48, and 3.96, respectively.…”

Role of antiviral therapy in patients with chronic hepatitis B or C virus in preventing the development of hepatocellular carcinoma

“…The lower rate of underlying cirrhosis in HBV-related HCCs as compared to other etiologies argues for a more direct role of HBV in the oncogenetic process. [8] The molecular and genetic features of HBV chronic infection involving cancer development could be summarized into (1) Pre-core and basal core promoter mutations, genotype B and C [9][10][11][12][13] and (2) integration of HBV DNA into the host genome and the expression of HBV proteins such as surface proteins and the X protein. [14][15][16] Studies on the natural history of chronic HBV infection have shown that active HBV replication contributes to the development of acute hepatitis flare, hepatic decompensation, cirrhosis, and HCC.…”

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

“…As for pre-S deletion, it was (Gao et al, 2007) reported that these mutations were more commonly found in the patients with HCC that in the chronic hepatitis B or asymptomatic carrier, suggesting pre-S deletion might involved in HBV-related hepatocarinogenesis. Mutations in basal core promoter may also involved in the development of carcinoma, the result of direct sequencing revealed that mutations including A1896, A1899 and multiple mutations T1762/A1764+A1896, T1762/A1764+A1899, and T1762/A1764+A1896+A1899 were more common in cirrhotic hepatocellular carcinoma group and non-cirrhotic hepatocellular carcinoma than chronic hepatitis B patients (Zheng et al, 2011). Moreover, a study with 37 patients and 38 controls has been performed and reported G1613A and C1653T double mutations were more prevalent in patients with HCC, thus, those mutations may serve as makers in predicting HCC development (Tatsukawa et al, 2011).…”