Wasmuth Hermann E, Stolte Christian, Geier Andreas, Dietrich Christoph G, Gartung Carsten, Lorenzen Johann, Matern Siegfried, Lammert Frank
Department of Internal Medicine III, University Hospital Aachen (UKA), Aachen University (RWTH), Aachen, Germany.
BMC Infect Dis. 2004 Feb 13;4:4. doi: 10.1186/1471-2334-4-4.
Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies.
Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related to demographic variables and to the outcome of antiviral combination therapy with interferon-alpha and ribavirin in 65 patients.
In our study, positivity for autoantibodies was associated with higher alanine aminotransferase levels and higher mean values for HCV-RNA (p < 0.01). Furthermore, negativity for non-organ-specific autoantibodies was associated with a favourable treatment outcome of combination therapy with at least one negative RT-PCR for HCV-RNA during treatment (OR 4.65, 95% CI 1.31 to 16.48, p = 0.02). ANA and SMA staining patterns and titers were not correlated to treatment response. With multiple logistic regression analysis, positivity for autoantibodies and HCV genotype were independently associated with outcome of antiviral combination therapy (p = 0.02).
The absence of non-organ-specific autoantibodies might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. Therefore, despite of an overall higher treatment response, the addition of the immunomodulatory drug ribavirin could accentuate immunological differences that affect treatment outcome and might have been less obvious in earlier studies analysing interferon monotherapy.
在相当数量的抗丙型肝炎病毒(HCV)阳性患者中可检测到非器官特异性自身抗体。以往研究探讨了这些抗体在接受干扰素单一疗法患者中的临床相关性,但未涉及联合疗法。
采用间接免疫荧光法检测了78例连续的抗HCV阳性患者的抗核抗体、抗平滑肌抗体、抗线粒体抗体、抗中性粒细胞胞浆抗体及抗肝肾微粒体抗体。这些抗体的存在与人口统计学变量以及65例接受α干扰素和利巴韦林抗病毒联合治疗患者的治疗结果相关。
在我们的研究中,自身抗体阳性与较高的丙氨酸转氨酶水平及较高的HCV-RNA平均值相关(p<0.01)。此外,非器官特异性自身抗体阴性与联合治疗的良好治疗结果相关,即治疗期间至少有一次HCV-RNA逆转录-聚合酶链反应(RT-PCR)结果为阴性(比值比4.65,95%可信区间1.31至16.48,p=0.02)。抗核抗体(ANA)和抗平滑肌抗体(SMA)的染色模式及滴度与治疗反应无关。通过多因素逻辑回归分析,自身抗体阳性和HCV基因型与抗病毒联合治疗结果独立相关(p=0.02)。
不存在非器官特异性自身抗体可能表明慢性丙型肝炎感染患者接受联合治疗后病毒清除的机会显著增加。因此,尽管总体治疗反应较高,但添加免疫调节药物利巴韦林可能会加剧影响治疗结果的免疫差异,而这种差异在早期分析干扰素单一疗法的研究中可能不太明显。