Hanouneh Ibrahim A, Miller Charles, Aucejo Federico, Lopez Rocio, Quinn Mary Kay, Zein Nizar N
Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Liver Transpl. 2008 Jan;14(1):53-8. doi: 10.1002/lt.21312.
Sustained virologic response (SVR) in the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) remains suboptimal. We evaluated efficacy of pegylated interferon alfa (PEG) and ribavirin (RBV) (PEG/RBV) combination therapy in LT recipients with recurrent HCV and predictive values of rapid virological response (RVR) and early virologic response (EVR). Between January 2001 and October 2005, LT recipients with recurrent HCV were intended to be treated for 48 weeks with PEG/RBV combination therapy independent of genotype or virologic response [53 patients (79% genotype 1)]. On-treatment predictor of response at week 4 (RVR) was defined as undetectable HCV RNA, and at week 12 (EVR) as undetectable HCV RNA or a >2 log(10) drop from pretreatment viral load. SVR was seen in 19 (35%) patients. Patients with genotype 2/3 were more likely to achieve SVR than those with genotype 1 (87% versus 23%; P = 0.001). The highest rate of SVR was seen in patients with RVR [specificity and positive predictive value (PPV) = 100%] while the highest rate of treatment failure was seen in those who did not have EVR [sensitivity and negative predictive value (NPV) = 100%]. The NPV of RVR to identify those who will not achieve SVR was also very high (88%). EVR had low PPV (63%) to identify those with SVR. In conclusion, PEG/RBV combination therapy is effective in the treatment of post-LT recurrent HCV. On-treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity. Given its high PPV and NPV, RVR appears to be the most appropriate decision time point for continuation of therapy.
肝移植(LT)后复发性丙型肝炎病毒(HCV)感染治疗中的持续病毒学应答(SVR)仍不尽人意。我们评估了聚乙二醇化干扰素α(PEG)联合利巴韦林(RBV)(PEG/RBV)治疗肝移植受者复发性HCV的疗效以及快速病毒学应答(RVR)和早期病毒学应答(EVR)的预测价值。在2001年1月至2005年10月期间,复发性HCV的肝移植受者不论基因型或病毒学应答情况,均采用PEG/RBV联合疗法治疗48周[53例患者(79%为1型基因型)]。治疗第4周时的应答预测指标(RVR)定义为HCV RNA检测不到,第12周时(EVR)定义为HCV RNA检测不到或较治疗前病毒载量下降>2 log(10)。19例(35%)患者实现了SVR。2/3型基因型患者比1型基因型患者更易实现SVR(87%对23%;P = 0.001)。RVR患者的SVR率最高[特异性和阳性预测值(PPV)= 100%],而未出现EVR的患者治疗失败率最高[敏感性和阴性预测值(NPV)= 100%]。RVR用于识别不能实现SVR患者的NPV也很高(88%)。EVR识别SVR患者的PPV较低(63%)。总之,PEG/RBV联合疗法对肝移植后复发性HCV治疗有效。治疗期间的病毒学监测对SVR具有高度预测性,可优化病毒学应答并将毒性降至最低。鉴于其高PPV和NPV,RVR似乎是继续治疗最合适的决策时间点。