Song Byung-Cheol, Cui Xiu Ji, Kim Heung Up, Cho Yoo-Kyung
Department of Internal Medicine, Cheju National University College of Medicine, Cheju National University Hospital, Jeju, Republic of Korea.
Intervirology. 2006;49(5):266-73. doi: 10.1159/000093456. Epub 2006 May 22.
Despite the pathogenic role of the basal core promoter (BCP) and the precore mutations in chronic hepatitis B virus (HBV) infection, their role in the progression of liver disease is still controversial. We analyzed whether the accumulation of these mutations might enhance the progression of HBV-related chronic liver disease.
Forty consecutive patients at each clinical status were analyzed. Clinical statuses were as follows: HBeAg-positive asymptomatic carrier (HBeAg(+) ASC) (defined as HBeAg(+), anti-HBe(-), HBV-DNA(+) by hybridization, normal ALT); inactive HBsAg carrier; chronic hepatitis B; liver cirrhosis. The genotype and the BCP/precore regions were determined by PCR using genotype specific primers and direct sequencing, respectively.
All patients except one were infected with genotype C. The A to T mutation at nucleotide 1762 and/or G to A mutation at nucleotide 1764 were found in 30% in HBeAg(+) ASC, 65.7% in inactive HBsAg carrier, 95% in chronic hepatitis B, and 90% in liver cirrhosis (p < 0.001). The prevalence of the G to A mutation at nucleotide 1896 was 5% in HBeAg(+) ASC, 22.5% in inactive HBsAg carrier, 32.5% in chronic hepatitis B, and 50% in liver cirrhosis, respectively (p < 0.001). The T to C/A mutation at nucleotide 1753 in the BCP and G to A mutation at nucleotide 1899 in the precore were more frequent in liver cirrhosis than in the other clinical statuses (p < 0.05).
Sequential accumulation of mutations in the BCP/precore has an important role in the progression of HBV-related liver disease.
尽管基础核心启动子（BCP）和前核心突变在慢性乙型肝炎病毒（HBV）感染中具有致病作用，但其在肝病进展中的作用仍存在争议。我们分析了这些突变的积累是否会加速HBV相关慢性肝病的进展。
对处于每种临床状态的40例连续患者进行分析。临床状态如下：HBeAg阳性无症状携带者（HBeAg(+) ASC）（定义为HBeAg(+)、抗-HBe(-)、通过杂交检测HBV-DNA(+)、ALT正常）；非活动性HBsAg携带者；慢性乙型肝炎；肝硬化。分别使用基因型特异性引物通过PCR和直接测序确定基因型以及BCP/前核心区域。
除1例患者外，所有患者均感染C基因型。在HBeAg(+) ASC中，1762位核苷酸A到T突变和/或1764位核苷酸G到A突变的发生率为30%，在非活动性HBsAg携带者中为65.7%，在慢性乙型肝炎中为95%，在肝硬化中为90%（p < 0.001）。1896位核苷酸G到A突变的发生率在HBeAg(+) ASC中为5%，在非活动性HBsAg携带者中为22.5%，在慢性乙型肝炎中为32.5%，在肝硬化中为50%，差异均有统计学意义（p < 0.001）。BCP区域1753位核苷酸T到C/A突变和前核心区域1899位核苷酸G到A突变在肝硬化中的发生率高于其他临床状态（p < 0.05）。
BCP/前核心区域突变的序贯积累在HBV相关肝病的进展中起重要作用。
