Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen‐positive hepatocellular carcinoma: a comparison with chronic carriers

Abstract

Background: Chronic hepatitis B virus (HBV) infection is associated with hepatocellular carcinoma (HCC), and specific viral factors have been identified that may increase the risk for HCC development. However, the differences in these viral factors in chronic carriers who seldom develop HCC compared with HCC patients have not been adequately evaluated. Methods: From 1989 to 2005, 101 hepatitis B surface antigen-positive patients presented to our clinic with HCC. Baseline basal core promoter (BCP) T1762/A1764 mutants, precore (PC) A1896 mutants, HBV genotypes and HBV DNA in HCC patients were compared with 67 chronic carriers who had been followed for a mean of 112.1 AE 77.7 standard deviation months. Results: At baseline, HCC patients had lower levels of serum albumin, but higher values of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin and a-foetoprotein than those of chronic carriers (P o 0.001 for all comparisons). The presence of genotype C, higher frequencies of PC A1896 mutants, BCP T1762/A1764 mutants and higher circulating levels of HBV DNA were more frequently detected in HCC patients than that in chronic carriers (P o 0.001 for all observations). Logistic regression analysis revealed that BCP T1762/A1764 mutants [odds ratio (OR) 11.14, 95% confidence interval (CI) 3.05-40.72; P o 0.001] and PC A1896 mutants (OR 3.75, 95% CI 1.14-12.34; P o 0.05) were significantly associated with HCC development. Conclusion: Our results indicate that the presence of BCP and PC mutations significantly increases the risk for HCC in chronic hepatitis B patients. These mutations were less often detected in chronic carriers who seldom develop HCC.Hepatocellular carcinoma (HCC) is a common malignancy in many areas of the world (1). The largest concentrations of HCC cases are in Asia and in Africa, where over 80% of liver cancer cases are reported. In these countries, the most important aetiology for HCC is chronic hepatitis B virus (HBV) infection, and strong geographical correlations have been reported between the incidence of HCC and the prevalence of HBV infections in these areas.

A case–control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma

“…For instance, a Taiwanese study showed that the presence of the PC mutation significantly increased the risk for HCC [9], while another community-based cohort study with long-term follow-up conducted in the same country demonstrated that this mutant was associated with a decreased risk of HCC development [24]. In this study, our data showed that this common variant might not account for the increased risk of HCC among Thai populations.…”

“…The other common HBV variants include double mutations in the basal core promotor (BCP) region (A1762T/ G1764A), which overlap with the ORF of the X gene and result in substantial decreases in HBeAg production [5]. These dual mutants have been reported in up to 50-80% of patients with HBeAg-negative chronic hepatitis B in Europe and Asia [6], and have been implicated in HCC development [7][8][9]. Apart from these variants, other mutations, such as T1753C/A/G in the BCP region and C1653T in the enhancer II region (EnhII) have become increasingly recognized as being associated with the outcome of chronic HBV infection, including HCC development [10][11][12].…”

Treatment recommendations for chronic hepatitis B

“…11,30 Other studies have shown that basal core promoters T1762/ A1764 mutants were more frequently detected in HCC patients and in patients with decompensated liver disease. 31-,34 The role of precore A1896 mutants is less clear.…”

Distribusi Genotipe dan Subtipe Virus Hepatitis B pada Penderita Hepatitis B Kronik di Pekanbaru

“…Mutasi pada daerah precore ini sering ditemukan pada penderita hepatitis B kronik dengan HBeAg negatif dan telah dilaporkan berhubungan dengan terjadinya KH pada penderita hepatitis B kronik. 18 Untuk memperoleh informasi lebih lanjut tentang pengaruh varian VHB pada perjalanan penyakit hepatitis B kronik perlu dilakukan penentuan frekuensi mutasi ini pada berbagai genotipe VHB. Sebagai informasi awal, penelitian yang dilakukan oleh peneliti pada tahun 2006 didapatkan mutan precore pada 93% penderita hepatitis B kronik aktif dan 73% donor darah.…”