Knolle P A, Kremp S, Höhler T, Krummenauer F, Schirmacher P, Gerken G
First Department of Medicine, Johannes Gutenberg Universität, Mainz, Germany.
J Viral Hepat. 1998 Nov;5(6):399-406. doi: 10.1046/j.1365-2893.1998.00127.x.
Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.
丙型肝炎病毒（HCV）急性感染后，约50 - 70%的患者会发展为慢性肝炎。用α干扰素（IFN-α）治疗这些患者，仅有15 - 20%能获得持续的长期缓解，且更高比例的患者会出现大量不良副作用。我们研究的目的是确定宿主或病毒参数，以便在治疗开始前识别对IFN-α治疗有反应者和无反应者。我们研究了一组87例接受IFN-α治疗的慢性丙型肝炎患者。经过长期随访，18例患者（21%）在治疗停止后长达7年的时间里对IFN-α治疗表现出持续反应（血清转氨酶正常化且血清中病毒RNA消失）。通过单变量和多变量分析，未发现宿主因素可预测治疗反应。治疗前肝活检样本中的炎症或纤维化程度以及免疫遗传因素（主要组织相容性复合体II单倍型和肿瘤坏死因子-α启动子多态性）均与治疗反应无关。相比之下，病毒参数与治疗反应密切相关。在有反应者中，HCV基因型3的出现频率显著更高（P = 0.034），有反应者的平均HCV RNA浓度（3.1×10⁴）低于无反应者（2.5×10⁵）（P = 0.01）。通过多变量分析，HCV基因型和HCV RNA浓度均为治疗反应的独立预测因素。然而，仅根据治疗前病毒RNA浓度或病毒基因型无法准确预测个体患者的治疗反应。发现与治疗反应最佳的关联是治疗开始3个月后血清中HCV RNA的清除情况（34例部分和持续反应者中有32例，53例无反应者中无1例；P = 0.001）。总之，治疗前病毒因素的测定与治疗反应显著相关，但对患者而言并不能给出准确预测，而治疗3个月后血清中HCV RNA的清除可预测治疗反应，而宿主因素则不然。
