Saitoh Y, Miura M, Niitsuma H, Numata N, Ohori H, Ishii M, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Tohoku J Exp Med. 1994 Aug;173(4):361-9. doi: 10.1620/tjem.173.361.
To assess the efficacy of repeated interferon (IFN) administration in patients with chronic hepatitis C unresponsive to initial therapy, serum hepatitis C virus (HCV)-RNA levels were measured in 12 patients who had failed prior IFN therapy. Serum HCV-RNA was assayed by measuring DNA complementary to HCV-RNA using a quantitative reverse transcription-polymerase chain reaction assay. The mean total dose of IFN was 227.8 mega-units for first treatment and 270.7 mega-units for second treatment. Five responders with a normal alanine aminotransferase (ALT) concentration (less than 40 IU/liter) at the end of the first treatment also had a normal ALT concentration at the end of the second treatment. By contrast, all nonresponders with an elevated ALT concentration during the first treatment likewise had an elevated ALT concentration at the end of the second treatment. HCV-RNA levels before the first treatment varied from 10(6) to 10(8) copies/microliters. The serum HCV-RNA levels fell in 9 out of 10 patients after the first treatment and in 11 out of 12 patients after the second treatment. One patient had unchanged normal serum ALT levels after two courses of IFN treatment. These results suggested that the outcome of a second course of IFN treatment was similar biochemically and virologically to a first course, and that patients who did not respond initially seldom respond to additional IFN therapy. Therefore, readministration of IFN should be restricted to patients who respond biochemically and virologically to initial treatment. The optimal second dose shall be determined with further studies.
为评估反复给予干扰素(IFN)对初始治疗无反应的慢性丙型肝炎患者的疗效,我们对12例先前IFN治疗失败的患者检测了血清丙型肝炎病毒(HCV)-RNA水平。采用定量逆转录-聚合酶链反应测定法,通过测量与HCV-RNA互补的DNA来检测血清HCV-RNA。首次治疗的IFN平均总剂量为227.8百万单位,第二次治疗为270.7百万单位。5例在首次治疗结束时丙氨酸转氨酶(ALT)浓度正常(低于40 IU/升)的反应者在第二次治疗结束时ALT浓度也正常。相比之下,所有在首次治疗期间ALT浓度升高的无反应者在第二次治疗结束时ALT浓度同样升高。首次治疗前HCV-RNA水平在10⁶至10⁸拷贝/微升之间。10例患者中有9例在首次治疗后血清HCV-RNA水平下降,12例患者中有11例在第二次治疗后下降。1例患者在两个疗程的IFN治疗后血清ALT水平未改变且仍正常。这些结果表明,IFN第二疗程的生化和病毒学结果与第一疗程相似,且最初无反应的患者很少对额外的IFN治疗有反应。因此,IFN的再次给药应限于那些在生化和病毒学上对初始治疗有反应的患者。最佳的第二次剂量有待进一步研究确定。