High-dose interferon-α2b treatment prevents chronicity in acute hepatitis C
High-dose interferon-α2b treatment prevents chronicity in acute hepatitis C
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高剂量干扰素-α2b 治疗可预防急性丙型肝炎的慢性化
DOI：
10.1007/bf02087880
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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：
--
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。为了评价大剂量干扰素治疗的疗效，我们在1992年开始了一项试验性研究，使用10 MU干扰素-α 2b，每天皮下注射，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。随访6 ~ 29个月（平均19.5±10.4个月），除2例脱落和2例HCV-RNA阴性3个月和8个月后复发外，所有患者的血清ALT浓度均保持正常，HCV-RNA均为阴性。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例PCR阳性患者中，9例HCV-RNA（Quantiplex; Chiron，Emeryville，加州）浓度<3.5× 105 eq/ml。在其他5例患者中，浓度范围为10.4× 105 eq/ml至131.6× 105 eq/ml（平均值=69.6×105）。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%）持续HCV-RNA阴性18.65（±9.7）个月。这些结果表明，大剂量干扰素-α2bis耐受性良好，可有效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-α2badministered 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 <3.5×105eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4×105eq/ml to 131.6×105eq/ml (mean=69.6×105). 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-α2badministered 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-α2bis well tolerated and effective in preventing a chronic course of hepatitis C infection.