Utsumi Takako, Aksono Eduardus Bimo, Yano Yoshihiko, Hayashi Yoshitake, Hotta Hak, Rantam Fedik Abdul, Kusumobroto Hernomo Ontoseno, Lusida Maria Inge
Department of Microbiology, School of Medicine, Airlangga University, Surabaya, East Java 60131; ; Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University;
Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University; ; Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan ;
Biomed Rep. 2013 Jul;1(4):522-528. doi: 10.3892/br.2013.106. Epub 2013 May 15.
Chronic hepatitis B virus (HBV) infection is a major health problem worldwide, with a particularly high prevalence in the Asian-Pacific region. During chronic hepatitis B virus (HBV) infection, mutations commonly occur in the basal core promoter (BCP) and precore (PC) regions of HBV, affecting HBeAg expression, particularly following HBeAg serocon-version. Mutations in the B- and T-cell epitopes of the HBV core have also been observed during disease progression. The clinical significance of HBV genome variability has been demonstrated, however the results are a subject of controversy. Considering the characteristics of the virus associated with geographical location, the profiles of BCP, PC and core mutations and their clinical implications in patients with chronic HBV infection in Surabaya, Indonesia, were investigated. The BCP, PC and core mutations and HBV genotypes were detected by direct sequencing. The HBeAg/anti-HBe status and HBV DNA levels were also assessed. This study enrolled 10 patients with chronic HBV infection (UC) from Dr Soetomo General Hospital and Indonesian Red Cross, Surabaya, East Java, Indonesia, 10 patients with chronic hepatitis B and liver cirrhosis (LC) and 4 patients with chronic hepatitis B and hepatocellular carcinoma (HCC) from Dr Soetomo General Hospital. The PC mutation A1896 was predominant in all the groups (60-100%), together with the PC variant T1858, which was associated with HBV genotype B. The number of detected core mutations (Thr/Ser130) was higher in HCC patients (50%). However, the BCP mutations T1762/A1764 were predominant in LC patients (50-60%). The LC and HCC patients carried HBV isolates with additional mutations, at least at BCP or PC, mainly following HBeAg seroconversion. In the majority of anti-HBe-positive samples, the BCP T1762/A1764 mutations were associated with a high viral load, regardless of the PC 1896 status. In conclusion, the PC mutations were found to be predominant in all the groups. However, the BCP mutations were mainly detected in the LC group and may be considered as a critical indicator of a poor clinical outcome.
慢性乙型肝炎病毒（HBV）感染是全球主要的健康问题，在亚太地区尤为高发。在慢性乙型肝炎病毒（HBV）感染期间，HBV的基础核心启动子（BCP）和前核心（PC）区域通常会发生突变，影响HBeAg表达，尤其是在HBeAg血清学转换之后。在疾病进展过程中也观察到HBV核心的B细胞和T细胞表位发生突变。HBV基因组变异性的临床意义已得到证实，但其结果仍存在争议。考虑到与地理位置相关的病毒特征，本研究调查了印度尼西亚泗水慢性HBV感染患者中BCP、PC和核心突变的情况及其临床意义。通过直接测序检测BCP、PC和核心突变以及HBV基因型。同时评估HBeAg/抗-HBe状态和HBV DNA水平。本研究纳入了来自印度尼西亚东爪哇泗水苏托莫综合医院和印度尼西亚红十字会的10例慢性HBV感染（UC）患者、10例慢性乙型肝炎和肝硬化（LC）患者以及来自苏托莫综合医院的4例慢性乙型肝炎和肝细胞癌（HCC）患者。PC突变A1896在所有组中占主导地位（60%-100%），同时还有与HBV B基因型相关的PC变异T1858。HCC患者中检测到的核心突变（Thr/Ser130）数量更高（50%）。然而，BCP突变T1762/A1764在LC患者中占主导地位（50%-60%）。LC和HCC患者携带的HBV分离株至少在BCP或PC处有额外突变，主要发生在HBeAg血清学转换之后。在大多数抗-HBe阳性样本中，无论PC 1896状态如何，BCP T1762/A1764突变都与高病毒载量相关。总之，PC突变在所有组中均占主导地位。然而，BCP突变主要在LC组中检测到，可被视为临床预后不良的关键指标。
