Laboratory of Molecular Virology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.
J Med Virol. 2014 Feb;86(2):217-23. doi: 10.1002/jmv.23837. Epub 2013 Nov 6.
Most cases of hepatocellular carcinoma (HCC) are due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. The aim of this study was to determine the viral genotypes and frequency of 17 mutations (15 for HBV and 2 for HCV), described previously as able to influence the course of chronic liver disease, in patients with and without HCC. This transversal study included 157 Brazilian patients with chronic hepatitis B (n = 51) and C (n = 106). Of these, 12 and 40 patients had HBV- and HCV-related HCC, respectively. Nucleotide sequencing of core promoter, pre-core, and pre-S/S regions of HBV and core region of HCV strains was performed to determine their genotypes and the frequency of the respective mutations. Among the HBV isolates, subgenotype A1 was the most prevalent in both patients with (90%) and without (61%) HCC. Fourteen out of the 15 mutations under study, as well as five different pre-S deletions, were identified. Core promoter T1753V, A1762T, and G1764A mutations were more frequent in patients with HCC than in those without, although with no statistical difference. However, a significant correlation was observed between T1753V mutation and elevation of transaminases levels (P < 0.05). As for HCV, mutation at residue 70 in the core protein of genotype 1b strains was significantly more frequent in patients with cirrhosis (56.3%) than in those without (9.1%) (P = 0.018). The detection of some key mutations in the genomes of HBV and HCV might be helpful to predict the clinical outcome of patients with chronic liver disease.
大多数肝细胞癌(HCC)病例是由于全球慢性乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)感染引起的。本研究旨在确定患有和不患有 HCC 的患者的病毒基因型和 17 种突变(HBV 为 15 种,HCV 为 2 种)的频率,这些突变先前被描述为能够影响慢性肝病的病程。这项横断面研究包括 157 名巴西慢性乙型肝炎(n=51)和丙型肝炎(n=106)患者。其中,12 名和 40 名患者分别患有 HBV 和 HCV 相关的 HCC。对 HBV 核心启动子、前核心和前 S/S 区以及 HCV 核心区的核苷酸序列进行测序,以确定其基因型和各自突变的频率。在 HBV 分离株中,亚基因型 A1 在患有 HCC(90%)和不患有 HCC(61%)的患者中最为流行。研究的 15 种突变中的 14 种以及 5 种不同的前 S 缺失均被鉴定出来。与不患有 HCC 的患者相比,患有 HCC 的患者中核心启动子 T1753V、A1762T 和 G1764A 突变更为常见,尽管差异无统计学意义。然而,观察到 T1753V 突变与转氨酶水平升高之间存在显著相关性(P<0.05)。至于 HCV,基因型 1b 株核心蛋白第 70 位残基的突变在肝硬化患者(56.3%)中明显比在无肝硬化患者(9.1%)中更为常见(P=0.018)。HBV 和 HCV 基因组中一些关键突变的检测可能有助于预测慢性肝病患者的临床结局。