Iwai A, Marusawa H, Takada Y, Egawa H, Ikeda K, Nabeshima M, Uemoto S, Chiba T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Viral Hepat. 2006 Aug;13(8):523-31. doi: 10.1111/j.1365-2893.2006.00760.x.
Patients with recurrent hepatitis C after liver transplantation usually have a high viral load and are generally resistant to interferon (IFN)-alpha2b plus ribavirin (RBV) therapy. However, it remains unclear whether pretreatment viral titre determines the effectiveness of combination therapy, especially in patients with a high viral load. The aim of this study was to identify the viral factors associated with a sustained virological response (SVR) to antiviral therapy in patients with recurrent hepatitis C after living-donor liver transplantation. Twenty-three patients with recurrent hepatitis C received combination therapy of IFN-alpha2b plus RBV. SVR was achieved in 7 of the 23 patients (30.4%). Predictive factors for SVR included a 2 log10 decline in Hepatitis C virus (HCV) RNA at 2 weeks after the start of therapy and disappearance of HCV RNA at 4 or 24 weeks after the start of therapy. As the pretreatment high viral load showed no association with SVR, we asked whether other viral factor was associated with the response to the combination therapy in transplant recipients. We found the several novel defective HCV clones in 4 of 12 recipients' sera. All defective HCV clones had deletions in the envelope region. Interestingly, no patients with defective clones showed a prompt decrease in HCV RNA after the start of IFN-alpha2b plus RBV therapy. Thus, early decline in serum HCV RNA after treatment was closely associated with SVR. The circulating defective HCV clones are present and might be associated with the response to the combination therapy in patients with recurrent hepatitis after liver transplantation.
肝移植后复发性丙型肝炎患者通常病毒载量较高，且一般对干扰素（IFN）-α2b加利巴韦林（RBV）治疗耐药。然而，预处理时的病毒滴度是否决定联合治疗的效果仍不清楚，尤其是在病毒载量高的患者中。本研究的目的是确定活体供肝肝移植后复发性丙型肝炎患者对抗病毒治疗产生持续病毒学应答（SVR）的相关病毒因素。23例复发性丙型肝炎患者接受了IFN-α2b加RBV的联合治疗。23例患者中有7例（30.4%）实现了SVR。SVR的预测因素包括治疗开始后2周丙型肝炎病毒（HCV）RNA下降2 log10以及治疗开始后4周或24周HCV RNA消失。由于预处理时的高病毒载量与SVR无关，我们探讨了其他病毒因素是否与移植受者对联合治疗的反应有关。我们在12例受者的血清中发现了4例存在几种新的缺陷型HCV克隆。所有缺陷型HCV克隆的包膜区域均有缺失。有趣的是，没有缺陷型克隆的患者在开始IFN-α2b加RBV治疗后HCV RNA没有迅速下降。因此，治疗后血清HCV RNA的早期下降与SVR密切相关。循环中的缺陷型HCV克隆存在，可能与肝移植后复发性肝炎患者对联合治疗的反应有关。
