丙型肝炎失代偿期肝硬化患者的抗病毒治疗及其长期临床结局

Antiviral treatment and long-term clinical outcome of decompensated cirrhotic patients with hepatitis C virus infection

目的 评估小剂量干扰素逐渐加量治疗丙型肝炎失代偿期肝硬化患者的疗效和安全性以及获得病毒学应答对长期预后的影响. 方法 前瞻性纳入2008年8月至2013年8月共66例丙型肝炎失代偿期肝硬化患者,从小剂量开始逐渐加量接受PEG-IFN α-2b/ PEG-IFN α-2a每周1次或普通干扰素隔日1次联合利巴韦林治疗48 ～ 72周,评估病毒学应答情况[包括持续病毒学应答（SVR）、治疗结束病毒学应答（ETVR）、复发和无应答].计量资料组间数据比较采用单因素方差分析、配对t检验,计数资料采用x2检验、Fisher＆#39;s确切概率法;患者随访期间肝癌发生以及患者生存比较采用生存曲线分析法（Kaplan-Meier curves）.结果 66例患者中49例治疗结束时HCV RNA阴性（ETVR）,30例（45.5％）获得SVR,19例（28.8％）复发,17例（25.7％）无应答.分别有65.9％和34.1％基因1型患者获得ETVR和SVR;90.9％和68.2％基因2型患者获得ETVR和SVR.早期病毒学应答（EVR）作为ETVR的阳性和阴性预测值分别为95.7％和75.0％;EVR作为SVR的阳性和阴性预测值分别为65.2％和100％.与治疗前比较,SVR和复发组患者肝功能包括总胆红素、ALT、白蛋白、凝血酶原活动度及Child-Pugh评分等明显改善（t值分别为4.564,11.486,2.303,2.699,3.694,P值均＜0.05）;与无应答组比较,SVR和复发组患者随访过程中肝功能失代偿与肝癌发生风险降低、生存时间延长（x2值分别为18.756,6.992,7.580,P值均＜0.05）.12例（18.2％）患者发生严重不良事件,2例死亡.结论 小剂量干扰素逐渐加量联合利巴韦林治疗丙型肝炎失代偿期肝硬化具有可行性,获得ETVR患者的长期预后明显改善.

Objective To investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus （HCV） infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.Methods Sixty-six consecutive,interferon （IFN）-na（i）ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study.All patients were given a 48-to 72-week course of IFN plus ribavirin （RBV） combined therapy,with a low accelerating dosage regimen using either：pegylated （PEG）-IFNα-2b at 1.0-1.5 μg/kg/week,PEG-IFNα-2a at 90-180 μg,or standard IFN-α-2b at 3MU,every other day.RBV was given at 800-1000 mg/day.All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.Results At the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response （NVR）.Among the patients with HCV genotype 1,65.9% achieved end-of-treatment virological response （ETVR） and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR.The positive and negative predictive values of early virological response （EVR） for ETVR were 95.7% and 75.0% respectively,and for SVR were 65.2% and 100% respectively.Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score （t =4.564,11.486,2.303,2.699,3.694 respectively,all P 〈 0.05）.Compared with the NVR patients,the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma,and had improved survival （x 2 =18.756,6.992,7.580,respectively,all P 〈 0.05）.Twelve （18.2%） patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.Conclusion Antiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.