High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study.
High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study.
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高剂量干扰素-α2b 治疗可预防急性丙型肝炎慢性化：一项试点研究。
DOI：
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发表时间：
1996
影响因子：
3.1
通讯作者：
J. Patsch
中科院分区：
文献类型：
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作者：
W. Vogel;I. Graziadei;F. Umlauft;C. Datz;F. Hackl;S. Allinger;K. Grünewald;J. Patsch
急性丙型肝炎在50-80%的病例中呈慢性病程。干扰素治疗的结果是相互矛盾的。为了评价高剂量干扰素治疗的疗效，我们在1992年开始了一项试点研究，每天皮下注射10 MU干扰素-α 2b，直到血清转氨酶浓度正常化。在确诊为急性丙型肝炎后开始治疗。在治疗前使用PCR检测HCV-RNA，在治疗的前两周每周检测三次，然后每周检测一次，直至治疗结束。在15个月的随访期间，HCV-RNA检测每月进行一次，直到第6个月，此后每两到三个月进行一次。在撰写本文时入组了24例患者;年龄范围为18 - 76岁（平均= 32），9例患者为男性。所有患者均表现为胆汁淤积性肝炎; 19名患者积极滥用静脉注射药物，4名患者无已知的胃肠外暴露，1名患者为医学实验室技术人员。所有患者抗-HCV阳性，HCV-RNA阳性，HIV阴性。5名患者感染基因型3，5名感染基因型1a，5名感染基因型1b，3名感染基因型3和2，1名感染基因型1和2。所有患者在18-43天内表现出正常的血清转氨酶浓度; HCV-RNA在所有患者中在4-12天内变为阴性。毒性不超过1级，并在治疗3天内消失。在随访期间，范围从6至29个月（平均= 19.5 +/- 10.4），血清ALT浓度保持正常，HCV-RNA保持阴性，在所有患者中，除了两个辍学和两个病人谁开发复发疾病后，HCV-RNA阴性的3个月和8个月，分别。在这两名患者中，再次出现了相同的HCV基因型3。血清ALT浓度范围为531至1940 IU/L（平均值= 1055;正常< 22）。在14名PCR阳性患者中，9名患者的HCV-RNA浓度（Quantiplex; Chiron，Emeryville，加州）< 3.5 x 10（5）eq/ml。其他5例患者的浓度范围为10.4 x 10（5）eq/ml至131.6 x 10（5）eq/ml（平均值= 69.6 x 10（5））。HCV-RNA浓度与就诊时血清ALT浓度（r = 0.331; P = 0.67）和ALT正常化前干扰素-α 2b总剂量（r = -0.088; P = 0.74）之间无相关性。24例患者中有22例完成了治疗（2例不依从）。其中，20例达到完全缓解（HCV-RNA阴性至少6个月）。其中2例复发，18例（90%）HCV-RNA保持阴性18.65（+/-9.7）个月。这些研究结果表明，高剂量干扰素-α 2b是耐受性良好，有效地预防慢性丙型肝炎感染。
Acute hepatitis C takes a chronic course in 50-80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-alpha2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested using PCR prior to treatment, three times weekly during the first two weeks of treatment, and then once weekly until the end of therapy. During the 15-month follow-up, HCV-RNA tests were performed monthly up to month 6 and every two to three months thereafter. Twenty-four patients were enrolled at the time of writing; age ranged from 18 to 76 years (mean = 32), and nine patients were men. All patients presented with cholestatic hepatitis; 19 were actively abusing intravenous drugs, four had no known parenteral exposure, and one was a medical laboratory technician. All patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five patients were infected with genotype 3, five with genotype 1a, five with genotype 1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized serum transaminase concentrations within 18-43 days; HCV-RNA became negative in all patients within 4-12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up period, which ranged from six to 29 months (mean = 19.5 +/- 10.4), serum ALT concentrations remained normal and HCV-RNA remained negative in all patients except two dropouts and two patients who developed relapsing disease after having been HCV-RNA negative for three and eight months, respectively. In both patients, the same HCV genotype 3 reemerged. Serum ALT concentrations ranged from 531 to 1940 IU/liter (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryville, California) were < 3.5 x 10(5) eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4 x 10(5) eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed between HCV-RNA concentrations and serum ALT concentrations at presentation (r = 0.331; P = 0.67) and total dose of interferon-alpha2b administered until normalization of ALT (r = -0.088; P = 0.74). Twenty-two of 24 patients completed treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) remained HCV-RNA negative for 18.65 (+/-9.7) months. These findings suggest that high-dose interferon-alpha2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.