Chen Chien-Hung, Lee Chuan-Mo, Lu Sheng-Nan, Changchien Chi-Sin, Eng Hock-Liew, Huang Chao-Min, Wang Jing-Houng, Hung Chao-Hung, Hu Tsung-Hui
Division of Hepatogastroenterology, Department of Internal Medicine, Kaoshiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
J Clin Microbiol. 2005 Dec;43(12):6000-6. doi: 10.1128/JCM.43.12.6000-6006.2005.
To assess the prevalence and clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations in Taiwan, a cohort of 200 Taiwanese chronic hepatitis B patients was analyzed. The HBV genotypes and sequences of the precore and the core promoter regions were determined in 66 asymptomatic carriers and 134 patients who had liver biopsy-verified chronic hepatitis and liver cirrhosis. The HBV e-antigen (HBeAg)-negative patients had a higher frequency of mutations at core promoter nucleotides 1753 and 1773 and precore nucleotides 1846, 1896, and 1899 than HBeAg-positive patients. Among the 200 patients, the frequencies of genotype C, T1762 and A1764, C1753, T1766 and A1768, and A1896 mutations increased and the frequencies of T or G1752, T1773, G1799, and C1858 mutations decreased with advancing liver diseases. These factors were different between those with HBeAg-positive status and those with HBeAg-negative status. Based on multiple logistic regression analysis, the risk factors of liver cirrhosis for 200 patients were the presence of T1762 and A1764 mutations (odds ratio [OR] = 11.11; 95% confidence interval [CI] = 3.91 to 31.25; P < 0.001), age > or =35 years (OR = 3.42; 95% CI = 1.33 to 8.77; P = 0.011), and genotype C (OR = 2.87; 95% CI = 1.21 to 6.81; P = 0.017). Further categorical analysis found that 62.1% of patients with genotype C, T1762 and A1764 mutations and age > or =35 years had liver cirrhosis. None of the 55 patients infected with the genotype B, A1762 and G1764 wild type and age <35 years showed liver cirrhosis. In conclusion, our data suggest that pathogenic differences between HBeAg-positive and -negative patients may exist. In Taiwan, HBV genotype C and the T1762 and A1764 mutations may play a role in HBV-related liver cirrhosis, and these could serve as molecular markers for prediction of the clinical outcomes of chronic HBV patients.
为评估台湾地区乙型肝炎病毒（HBV）基因型以及前核心和核心启动子突变的流行情况及其临床意义，对一组200例台湾慢性乙型肝炎患者进行了分析。在66例无症状携带者以及134例经肝活检证实为慢性肝炎和肝硬化的患者中，确定了HBV基因型以及前核心和核心启动子区域的序列。与HBeAg阳性患者相比，HBeAg阴性患者在核心启动子核苷酸1753和1773以及前核心核苷酸1846、1896和1899处的突变频率更高。在这200例患者中，随着肝病进展，基因型C、T1762和A1764、C1753、T1766和A1768以及A1896突变的频率增加，而T或G1752、T1773、G1799和C1858突变的频率降低。这些因素在HBeAg阳性状态和HBeAg阴性状态的患者之间有所不同。基于多因素逻辑回归分析，200例患者发生肝硬化的危险因素为存在T1762和A1764突变（比值比[OR]=11.11；95%置信区间[CI]=3.91至31.25；P<0.001）、年龄≥35岁（OR=3.42；95%CI=1.33至8.77；P=0.011）以及基因型C（OR=2.87；95%CI=1.21至6.81；P=0.017）。进一步的分类分析发现，62.1%的基因型C、T1762和A1764突变且年龄≥35岁的患者患有肝硬化。55例感染基因型B、A1762和G1764野生型且年龄<35岁的患者均未出现肝硬化。总之，我们的数据表明HBeAg阳性和阴性患者之间可能存在致病性差异。在台湾地区，HBV基因型C以及T1762和A1764突变可能在HBV相关肝硬化中起作用，并且这些可作为预测慢性HBV患者临床结局的分子标志物。
