Yeh B I, Han K H, Oh S H, Kim H S, Hong S H, Oh S H, Kim Y S
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
J Med Virol. 1996 Jun;49(2):95-102. doi: 10.1002/(SICI)1096-9071(199606)49:2<95::AID-JMV5>3.0.CO;2-E.
Ten patients with hepatitis C virus (HCV) infection (experimental group) were treated with interferon-alpha (IF-alpha). Dosage was six million units per day for one week and then three times a week for another six months. Seven HCV-infected patients (control group) did not receive IF-alpha therapy. The hypervariable region (HVR) of HCV in the sera of patients was amplified by reverse transcription-polymerase chain reaction (RT-PCR), and the variation of amino acid sequence in this region was determined. Serum alanine aminotransferase (ALT) activities in five patients treated for six months with IF-alpha fell to the normal range, when HCV was not detected in the sera of three patients. The nucleotide sequence variation in HVR of HCV in the sera of five patients who responded well to the IF-alpha therapy was relatively less than that in another five patients who did not respond to IF-alpha therapy and those in the control patients. These results indicate that the effectiveness of IF-alpha therapy was related to the sequence variation of HVR of HCV. This may have resulted from the selection pressure by humoral antibodies directed to HVR of HCV. It is concluded that the higher rate of sequence variation in HVR of HCV was compatible with a lower degree of effectiveness of IF-alpha therapy.
十名丙型肝炎病毒（HCV）感染患者（实验组）接受了α干扰素（IF-α）治疗。剂量为每天600万单位，持续一周，然后每周三次，持续另外六个月。七名HCV感染患者（对照组）未接受IF-α治疗。通过逆转录聚合酶链反应（RT-PCR）扩增患者血清中HCV的高变区（HVR），并确定该区域氨基酸序列的变异。五名接受IF-α治疗六个月的患者血清丙氨酸氨基转移酶（ALT）活性降至正常范围，其中三名患者血清中未检测到HCV。对IF-α治疗反应良好的五名患者血清中HCV的HVR核苷酸序列变异相对小于另外五名对IF-α治疗无反应的患者以及对照组患者。这些结果表明，IF-α治疗的有效性与HCV的HVR序列变异有关。这可能是由针对HCV的HVR的体液抗体的选择压力导致的。得出结论，HCV的HVR中较高的序列变异率与IF-α治疗的较低有效性程度相符。
