巴西流行的乙型肝炎病毒中的基础核心启动子和前核心突变及其与严重肝病形式的关联。
Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases.
作者信息
Chachá Silvana Gama Florencio, Gomes-Gouvêa Michele Soares, Malta Fernanda de Mello, Ferreira Sandro da Costa, Villanova Márcia Guimarães, Souza Fernanda Fernandes, Teixeira Andreza Correa, Passos Afonso Dinis da Costa, Pinho João Renato Rebello, Martinelli Ana de Lourdes Candolo
机构信息
Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brasil.
Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Clínica Médica, Divisão de Gastroenterologia, Ribeirão Preto, SP, Brasil.
出版信息
Mem Inst Oswaldo Cruz. 2017 Sep;112(9):626-631. doi: 10.1590/0074-02760160540.
BACKGROUND
In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV).
OBJECTIVES
This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease.
METHODS
A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced.
FINDINGS
PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03).
MAIN CONCLUSIONS
A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.
背景
在巴西，很少有研究调查过乙型肝炎病毒（HBV）前核心（PC）和核心启动子基础（BCP）突变体的感染率。
目的
本研究旨在分析HBV感染患者中PC和BCP突变的频率，并评估这些变异与晚期肝病之间的关联。
方法
共研究了161例HBV感染患者。为鉴定PC和BCP突变，对HBV DNA的一个501bp片段进行扩增和测序。
结果
分别在129例和118例中成功扩增并测序了HBV毒株的PC和BCP区域。PC和BCP突变分别在61.0%和80.6%的病例中被检测到。在1级和2级肝纤维化患者中，36.7%（29/79）鉴定出A1762T/G1764A变异；在3级和4级肝纤维化患者中，81.8%（9/11）鉴定出该变异（p<0.01）；在肝硬化患者中，76.9%（10/13）鉴定出该变异；在无肝硬化患者中，38.1%（40/105）鉴定出该变异（p=0.01）；在肝细胞癌（HCC）患者中，77.8%（7/9）鉴定出该变异；在无HCC患者中，39.4%（43/109）鉴定出该变异（p=0.03）。
主要结论
发现HBV PC和BCP突变体的感染率很高。A1762T/G1764A变异与晚期肝纤维化、肝硬化和HCC独立相关。
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