CAJ | 학술논문

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'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.
목적 평고소제량간우소축점가량치료병형간염실대상기간경화환자적료효화안전성이급획득병독학응답대장기예후적영향. 방법 전첨성납입2008년8월지2013년8월공66례병형간염실대상기간경화환자,종소제량개시축점가량접수PEG-IFN α-2b/ PEG-IFN α-2a매주1차혹보통간우소격일1차연합리파위림치료48 ～ 72주,평고병독학응답정황[포괄지속병독학응답(SVR)、치료결속병독학응답(ETVR)、복발화무응답].계량자료조간수거비교채용단인소방차분석、배대t검험,계수자료채용x2검험、Fisher's학절개솔법;환자수방기간간암발생이급환자생존비교채용생존곡선분석법(Kaplan-Meier curves).결과 66례환자중49례치료결속시HCV RNA음성(ETVR),30례(45.5％)획득SVR,19례(28.8％)복발,17례(25.7％)무응답.분별유65.9％화34.1％기인1형환자획득ETVR화SVR;90.9％화68.2％기인2형환자획득ETVR화SVR.조기병독학응답(EVR)작위ETVR적양성화음성예측치분별위95.7％화75.0％;EVR작위SVR적양성화음성예측치분별위65.2％화100％.여치료전비교,SVR화복발조환자간공능포괄총담홍소、ALT、백단백、응혈매원활동도급Child-Pugh평분등명현개선(t치분별위4.564,11.486,2.303,2.699,3.694,P치균＜0.05);여무응답조비교,SVR화복발조환자수방과정중간공능실대상여간암발생풍험강저、생존시간연장(x2치분별위18.756,6.992,7.580,P치균＜0.05).12례(18.2％)환자발생엄중불량사건,2례사망.결론 소제량간우소축점가량연합리파위림치료병형간염실대상기간경화구유가행성,획득ETVR환자적장기예후명현개선.
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.