Bizollon T, Palazzo U, Ducerf C, Chevallier M, Elliott M, Baulieux J, Pouyet M, Trepo C
Hepatology Unit, Hôtel-Dieu Hospital, Lyon, France.
Hepatology. 1997 Aug;26(2):500-4. doi: 10.1002/hep.510260236.
Recurrent hepatitis C virus (HCV) in liver transplant patients is a major cause of graft loss, liver failure, and need for retransplantation. The results available to date with the use of interferon alfa (IFN-alpha) in the treatment of recurrent HCV in liver transplant patients have been disappointing. The aim of this study was to evaluate the efficacy and clinical utility of post-transplant combination therapy with IFNalpha2b (3 million units 3 times weekly) and oral ribavirin (1,200 mg/d) for a duration of 6 months, followed by maintenance with ribavirin alone for an additional 6 months. Twenty-one liver transplant recipients with recurrent hepatitis C infection (HCV-RNA-positive; active hepatitis without rejection on biopsy) were enrolled in this study. Pretreatment serum alanine transaminase (ALT) levels were at least two times the upper limit of normal. Before treatment, all patients were HCV-RNA-positive and mean HCV-RNA titers were 125 million genome-equivalents/mL. Mean pretreatment histological score was 6.3 +/- 2. After 6 months of combination therapy, all 21 patients had normal ALTs. Ten patients (48%) cleared HCV-RNA from their serum, as assessed by polymerase chain reaction (PCR), and HCV-RNA levels decreased significantly in the others (P = .0001). Improvement in histological score was seen in all patients after combination therapy (P = .0013). During maintenance ribavirin monotherapy, ALT remained normal in all but 1 of the 18 patients who tolerated therapy. HCV-RNA reappeared in 5 patients, but HCV-RNA levels did not return to pretreatment levels (P = .0004). Comparison of pretreatment and postribavirin monotherapy liver biopsies revealed improvement in all but 1 of the 18 patients who tolerated ribavirin (P = .0002). Side effects were restricted to anemia, which necessitated cessation of ribavirin therapy in 3 patients. No patient experienced graft rejection during the study period. These results are significantly better than those reported with IFN-alpha monotherapy. Most importantly, there was a complete absence of graft rejection. These results suggest that the combination of IFN-alpha and ribavirin is effective in reducing HCV-RNA levels and ameliorating hepatocellular injury in recurrent HCV after liver transplantation, and that maintenance therapy with ribavirin monotherapy can maintain the biochemical and histological response.
肝移植患者的丙型肝炎病毒（HCV）复发是移植物丢失、肝衰竭及再次移植需求的主要原因。迄今为止，使用干扰素α（IFN-α）治疗肝移植患者HCV复发的结果令人失望。本研究的目的是评估移植后联合使用IFNα2b（300万单位，每周3次）和口服利巴韦林（1200mg/d）持续6个月，随后单独使用利巴韦林维持治疗6个月的疗效和临床实用性。21例丙型肝炎病毒复发感染的肝移植受者（HCV-RNA阳性；活检显示为无排斥反应的活动性肝炎）纳入本研究。治疗前血清丙氨酸转氨酶（ALT）水平至少为正常上限的两倍。治疗前，所有患者HCV-RNA均为阳性，平均HCV-RNA滴度为1.25亿基因组当量/mL。治疗前平均组织学评分为6.3±2。联合治疗6个月后，所有21例患者的ALT均恢复正常。通过聚合酶链反应（PCR）评估，10例患者（48%）血清HCV-RNA清除，其他患者的HCV-RNA水平显著下降（P = 0.0001）。联合治疗后所有患者的组织学评分均有改善（P = 0.0013）。在维持利巴韦林单药治疗期间，18例耐受治疗的患者中除1例之外，其余患者的ALT均保持正常。5例患者HCV-RNA再次出现，但HCV-RNA水平未恢复至治疗前水平（P = 0.0004）。比较治疗前和利巴韦林单药治疗后的肝活检结果显示，18例耐受利巴韦林治疗的患者中除1例之外，其余患者均有改善（P = 0.0002）。副作用仅限于贫血，3例患者因贫血需要停止利巴韦林治疗。研究期间无患者发生移植物排斥反应。这些结果明显优于IFN-α单药治疗的报道。最重要的是，完全没有移植物排斥反应。这些结果表明，IFN-α和利巴韦林联合使用可有效降低肝移植后HCV复发患者的HCV-RNA水平并改善肝细胞损伤，且利巴韦林单药维持治疗可维持生化和组织学反应。
