Zein N N, Rakela J, Krawitt E L, Reddy K R, Tominaga T, Persing D H
Mayo Clinic, Rochester, MN 55905, USA.
Ann Intern Med. 1996 Oct 15;125(8):634-9. doi: 10.7326/0003-4819-125-8-199610150-00002.
To study 1) the geographic distribution and clinical significance of hepatitis C virus (HCV) genotypes in the United States and 2) the influence of HCV genotypes on response to interferon therapy.
Hepatitis C virus genotype was determined in 179 stored serum samples obtained from patients who were positive for antibody to HCV and for HCV RNA by using polymerase chain reaction.
Tertiary referral centers in four geographic regions of the United States.
Patients who visited medical centers in the Midwest (50 patients), Northeast (42 patients), Southeast (35 patients), and West (52 patients).
Chaotropic lysis and isopropanol precipitation were used to extract RNA from serum. Polymerase chain reaction was done on the NS5 region and was followed by automated direct sequencing and genotyping of desalted amplification products.
104 patients (58%) had subtype 1a; 38 (21%) had subtype 1b; 4 (2%) had subtype 2a; 23 (13%) had subtype 2b; 8 (5%) had subtype 3a; and 2 (1%) had subtype 4a. Examination of the known risk factors for acquiring HCV showed no association between genotype and mode of acquisition (blood transfusion, injection drug use, employment at a health care facility) or histologic findings at presentation (mild active hepatitis, moderately active hepatitis, or cirrhosis). Sixty-eight percent of patients with genotype 1a, 80% of patients with genotype 1b, and 37% of patients with genotype 2a or 2b had severe hepatitis. Thirteen of 46 (28%) patients with genotype 1a and 4 of 15 (26%) patients with genotype 1b had a complete biochemical response after 6 months of interferon therapy. In contrast, 10 of 14 (71%) patients with genotype 2a or 2b had a complete response to interferon therapy. Five of 39 (13%) patients with genotype 1a, 1 of 14 (7%) patients with genotype 1b, and 2 of 11 (18%) patients with genotype 2a or 2b had a sustained biochemical response.
In the United States, HCV genotypes 1a and 1b are the predominant genotypes in patients with chronic hepatitis C. Genotype is not correlated with mode of virus acquisition or with histologic findings at presentation. Patients with HCV genotype 1a or 1b had more severe liver disease and lower rates of response to interferon therapy than did patients with HCV genotype 2a or 2b. These findings may have implications for predicting outcome and selecting patients for interferon treatment.
1）研究美国丙型肝炎病毒（HCV）基因型的地理分布及临床意义；2）研究HCV基因型对干扰素治疗反应的影响。
采用聚合酶链反应，对179份储存的血清样本进行HCV基因型测定，这些样本来自抗HCV抗体和HCV RNA均呈阳性的患者。
美国四个地理区域的三级转诊中心。
曾前往中西部（50例患者）、东北部（42例患者）、东南部（35例患者）和西部（52例患者）医疗中心就诊的患者。
采用离液剂裂解和异丙醇沉淀法从血清中提取RNA。对NS5区域进行聚合酶链反应，随后对脱盐扩增产物进行自动直接测序和基因分型。
104例患者（58%）为1a亚型；38例（21%）为1b亚型；4例（2%）为2a亚型；23例（13%）为2b亚型；8例（5%）为3a亚型；2例（1%）为4a亚型。对已知的HCV感染危险因素进行检查，结果显示基因型与感染方式（输血、注射吸毒、在医疗机构工作）或就诊时的组织学表现（轻度活动性肝炎、中度活动性肝炎或肝硬化）之间无关联。1a基因型患者中有68%、1b基因型患者中有80%、2a或2b基因型患者中有37%患有严重肝炎。46例1a基因型患者中有13例（28%）、15例1b基因型患者中有4例（26%）在接受6个月干扰素治疗后获得完全生化反应。相比之下，14例2a或2b基因型患者中有10例（71%）对干扰素治疗获得完全反应。39例1a基因型患者中有5例（13%）、14例1b基因型患者中有1例（7%）、11例2a或2b基因型患者中有2例（18%）获得持续生化反应。
在美国，HCV 1a和1b基因型是慢性丙型肝炎患者中的主要基因型。基因型与病毒感染方式或就诊时的组织学表现无关。与HCV 2a或2b基因型患者相比，HCV 1a或1b基因型患者的肝病更严重，对干扰素治疗的反应率更低。这些发现可能对预测预后和选择干扰素治疗患者具有重要意义。
