直接抗病毒药物治疗慢性丙型肝炎48周临床观察

背景慢性丙型肝炎(chronic hepatitis C,CHC)是全球公共卫生问题,随着直接抗病毒药(direct antiviral therapy,DAA)在中国的应用,DAA药物成为目前国内慢性丙型肝炎抗病毒一线方案,但目前真实世界DAA治疗后长期疗效数据尚少.目的观察慢性丙型肝炎患者接受直接抗病毒药物抗病毒治疗后48 wk病毒学应答及临床疗效.方法连续收集2018-04-01/2020-04-30在天津市第三中心医院接受DAA治疗的初治CHC患者,评估治疗基线、治疗结束、治疗后12 wk及48 wk的病毒学应答及肝肾功能、肝硬度、APRI及临床结局.结果共收集291例应用DAA治疗的CHC患者,纳入145例完成抗病毒治疗及随访的CHC患者进入本研究.其中肝硬化患者占28.3%,基因型1b、2a、3a、6a分别占78.0%、17.2%、2.8%、2.0%.DAA治疗结束、治疗后12 wk及48 wk获得持续病毒学应答(sustained virological response,SVR)比例分别为100%、97.9%和97.2%,其中基因型1b、2a、3a、6a的SVR48分别为97.3%、96%、100%、100%.治疗结束后48 wk与基线相比较,丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素及白蛋白的复常率分别为93.2%、91.7%、73.3%及97.7%.治疗结束后48 wk肝硬度(liver stiffness measurement,LSM)及APRI与基线水平相比均明显下降(LSM 12.5 vs 10.2kpa P<0.01;APRI 0.34 vs 0.13 P<0.01),肝硬化组及非肝硬化组患者均有明显下降(P<0.05).48 wk随访期间,其中4例(2.8%)CHC患者进展为肝硬化,8例(5.6%)肝硬化患者进展为肝硬化失代偿,3例(2.1%)肝硬化患者发生新发肝细胞癌(hepatocellular carcinoma,HCC).结论本研究真实世界中慢性丙型肝炎患者应用DAA治疗后48 wk,总体病毒持续应答率较高,肝功能、肝硬度及APRI值均明显改善.2.1%患者出现新发HCC.

Clinical effects of 48 weeks of direct antiviral therapy for chronic hepatitis C

BACKGROUND Chronic hepatitis C is a global public health problem.With the application of direct acting antiviral(DAA)drugs in China,DAA therapy has become the first-line antiviral regimen for chronic hepatitis C(CHC)in China.However,there is a lack of real-world long-term efficacy data after DAA treatment.AIM To observe the virological response and clinical efficacy of DAA therapy in patients with CHC.METHODS Patients with newly diagnosed chronic hepatitis C who received DAA treatment at Tianjin Third Central Hospital from April 1,2018 to April 30,2020 were collected continu-ously.The virological response,liver function,creatinine,liver stiffness,aspartate aminotransferase(AST)-platelet ratio index(APRI),and clinical outcomes were evaluated at baseline,12 and 48 wk after treatment,and the end of treatment.RESULTS A total of 291 patients with CHC treated with DAA were collected,of whom 145 completed antiviral therapy and were followed for 48 wk.The patients with liver cirrhosis accounted for 28.3%,and those infected by genotypes 1b,2a,3a,and 6A accounted for 78.0%,17.2%,2.8%,and 2.0%,respectively.The proportion of patients with sustained virological response(SVR)was 97.9%,97.2%,and 100%at 12 and 48-week after treatment and at the end of DAA treatment,respectively.The SVR at 48 wk in patients infected by genotypes 1b,2a,3a,and 6A was 97.3%,96%,100%,and 100%,respectively.Compared with baseline values,the normalization rates of alanine aminotransferase(ALT),AST,total bilirubin(TBIL),and albumin(ALB)were 93.2%,91.7%,73.3%,and 97.7%,respectively.After 48 wk of treatment,liver stiffness(LSM)and APRI were significantly decreased compared with baseline values(LSM:12.5 kpa vs 10.2 kpa,P<0.01;APRI:0.34 vs 0.13,P<0.01),and decreased significantly in both the cirrhotic group and non-cirrhotic group(P<0.05).During the 48-wk follow-up period,four(2.8%)patients with CHC progressed to cirrhosis,eight(5.6%)with cirrhosis progressed to decompensated cirrhosis,and three(2.1%)with cirrhosis developed hepatocellular carcinoma(HCC).CONCLUSION The overall SVR rate to 48 wk of DAA treatment in patients with chronic hepatitis C in the real world is higher,and liver function,liver stiffness,and APRI value can be significantly improved.A small portion of patients may develop HCC.