Watanabe Koji, Takahashi Toru, Takahashi Sumio, Okoshi Shogo, Ichida Takafumi, Aoyagi Yutaka
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
J Gastroenterol Hepatol. 2005 Mar;20(3):441-9. doi: 10.1111/j.1440-1746.2004.03572.x.
The clinicopathological profiles and outcome of chronic hepatitis B can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are two major HBV genotypes. The basic core promoter and precore mutations are other known viral factors for disease activity, although the relationship between HBV genotypes and these mutations is not fully understood.
The HBV genotypes in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained data were correlated with clinicopathological parameters, basic core promoter, precore and the nucleotide 1858 mutations of the HBV genome.
Among 90 cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B patients were older than genotype C patients (44.0 +/- 13.9 vs 34.7 +/- 11.0 P = 0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008) while anti-HBe was more common in genotype B than C patients (P = 0.0002). Serum aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 +/- 612.8/257.0 +/- 498.0 IU/L vs C: 111.3 +/- 122.8/201.6 +/- 229.4 IU/L, P = 0.16/0.48) and HBV viral loads in blood (B: 6.1 +/- 3.1 log genome equivalent [LGE]/mL vs C: 6.7 +/- 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion from HBeAg to anti-HBe occurred significantly earlier in genotype B than C patients (62 +/- 53 months vs 136 +/- 54 months, P = 0.0028) during the mean observation period of 149 +/- 82 months even under various therapeutic modalities. The categories III and IV of the histological activity index in genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B patients whereas category II was higher in genotype B than C patients (P < 0.05). The double mutation (1762T/1764A) in the basic core promoter was more frequently found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of 1858C that was complementary to the precore mutation site in the stem-loop structure in, was equally rare in both genotype B and C HBV.
Genotype B patients were older, had earlier HBeAg seroconversion and exhibited more severe lobular necroinflammation, less portal inflammation and fibrosis than genotype C patients. This genotypic difference is related to the basic core promoter and precore mutations irrespective of 1858C. (c) 2004 Blackwell Publishing Asia Pty Ltd.
慢性乙型肝炎的临床病理特征及转归可能因乙型肝炎病毒（HBV）基因型不同而有所差异。在日本，B型和C型是两种主要的HBV基因型。尽管HBV基因型与基本核心启动子及前核心区突变之间的关系尚未完全明确，但已知这些病毒因素与疾病活动相关。
采用酶联免疫吸附测定法（ELISA）对90例慢性乙型肝炎患者的HBV基因型进行检测。将所得数据与临床病理参数、基本核心启动子、前核心区及HBV基因组的1858位核苷酸突变进行相关性分析。
90例患者中，20例（22.2%）为B型HBV，70例（77.8%）为C型HBV。B型基因型患者的年龄大于C型基因型患者（44.0±13.9岁对34.7±11.0岁，P = 0.0022）。HBeAg在C型基因型患者中比B型基因型患者更常见（P = 0.0008），而抗-HBe在B型基因型患者中比C型基因型患者更常见（P = 0.0002）。血清天冬氨酸氨基转移酶/丙氨酸氨基转移酶水平（B型：220.7±612.8/257.0±498.0 IU/L对C型：111.3±122.8/201.6±229.4 IU/L，P = 0.16/0.48）及血液中的HBV病毒载量（B型：6.1±X.1 log基因组当量[LGE]/mL对C型：6.7±2.3 LGE/mL，P = 0.42）相当。在平均149±82个月的观察期内，即使采用各种治疗方式，B型基因型患者从HBeAg血清学转换为抗-HBe的时间也显著早于C型基因型患者（62±53个月对136±54个月，P = 0.0028）。C型基因型患者的组织学活动指数III级和IV级高于B型基因型患者（III级：P < 0.005，IV级：P < 0.05，n = 68），而B型基因型患者的II级高于C型基因型患者（P < 0.05）。基本核心启动子的双突变（1762T/1764A）在C型HBV中比在B型HBV中更常见（P = 0.0068），而前核心区突变（1896A）在B型HBV中比在C型HBV中更常见（P = 0.0233）。在茎环结构中与前核心区突变位点互补的1858C的发生率在B型和C型HBV中同样罕见。
B型基因型患者年龄较大，HBeAg血清学转换较早，与C型基因型患者相比，小叶坏死性炎症更严重，门脉炎症和纤维化程度较轻。这种基因型差异与基本核心启动子及前核心区突变有关，与1858C无关。（c）2004 Blackwell Publishing Asia Pty Ltd.
