直接抗病毒药物治疗慢性丙型肝炎肝硬化的回顾性分析

目的探讨直接抗病毒药物(direct-acting antiviral agent,DAA)治疗慢性丙型肝炎肝硬化患者实现持续病毒学应答(sustained virologic response,SVR)后的预后及转归。方法回顾性分析2014年1月至2017年6月于天津市第二人民医院临床诊断为慢性丙型肝炎肝硬化的95例患者,其中72例应用DAA获得SVR,23例未行抗病毒治疗,比较两组患者肝细胞癌发生率、病死率的差异。统计学分析采用独立样本t检验、曼-惠特尼U检验和χ²检验。结果在3~71个月的随访结束时,DAA治疗组丙氨酸转氨酶、天冬氨酸转氨酶、白蛋白、肝硬度测定值均较入组时改善42(23,61)U/L比18(13,28)U/L,54(37,75)U/L比23(18,28)U/L,39(33,42)g/L比45(41,48)g/L,26(18,37)kPa比15(11,26)kPa,Z=-6.005、-7.008、-6.057、-3.162,均P<0.01],但DAA治疗组与未行抗病毒治疗组患者肝细胞癌发生率12%(9/72)比17%(4/23)]、病死率3%(2/72)比13%(3/23)]差异均无统计学意义(均P>0.05)。应用DAA治疗和未行抗病毒治疗的慢性丙型肝炎肝硬化患者进行肝细胞癌累积发生率分析,两组差异无统计学意义(P=0.609)。慢性丙型肝炎肝硬化发生肝细胞癌患者与未发生肝细胞癌患者年龄(60.3±3.6)岁比(54.4±9.9)岁]差异有统计学意义(t=-3.948,P<0.01);代偿期肝硬化患者应用DAA治疗后,6例发生肝细胞癌的患者中4例患糖尿病,未发生肝细胞癌的患者糖尿病患病率为17%(7/42),发生肝细胞癌较未发生肝细胞癌者空腹血糖更高(7.3±1.9)mmol/L比(5.9±1.1)mmol/L],差异均有统计学意义(χ²=7.430,t=-2.442,P=0.019、0.019)。结论DAA可以显著改善慢性丙型肝炎肝硬化患者的肝功能、肝纤维化,但未发现可以改善其近期肝细胞癌发生率、病死率;空腹血糖升高、糖尿病可能为代偿期慢性丙型肝炎肝硬化患者发生肝细胞癌的危险因素。

A retrospective follow-up study of hepatitis C virus related cirrhosis treated with direct-acting antiviral agent

Objective To investigate the prognosis and outcome of patients with chronic hepatitis C(CHC)related cirrhosis after achieved sustained virologic response(SVR)treated with direct-acting antiviral agent(DAA).Methods Ninety-five patients diagnosed with CHC related cirrhosis who had complete data in Tianjin Second People′s Hospital from January 2014 to June 2017 were retrospectively followed up.Among them,72 patients were treated with DAA and all of them achieved SVR,and the other 23 patients did not receive any antiviral therapy.The differences of mortality and incidence of hepatocellular carcinoma(HCC)between DAA treatment group and non-antiviral treatment group were compared.Statistical analysis was performed by independent sample t test,Mann-Whitney U test and chi-square test.Results At the end of follow-up for three to 71 months,patients in DAA treatment group had a significant improvements in alanine aminotransferase,aspartate aminotransferase,albumin and liver stiffness measurement compared with those before treatment(42(23,61)U/L vs 18(13,28)U/L,54(37,75)U/L vs 23(18,28)U/L,39(33,42)g/L vs 45(41,48)g/L,26(18,37)kPa vs 15(11,26)kPa,respectively,Z=-6.005,-7.008,-6.057 and-3.162,respectively,all P<0.01).However,there were no significant differences in incidence of HCC(12%(9/72)vs 17%(4/23))and mortality(3%(2/72)vs 13%(3/23))between the DAA treatment group and non-antiviral treatment group(both P>0.05).There was no significant difference of cumulative incidence of HCC in DAA treatment group compared with non-antiviral treatment group(P=0.609).The age of patients progressed to HCC was older than those without HCC((60.3±3.6)years vs(54.4±9.9)years,t=-3.948,P<0.01).In subgroup analysis,among the six patients with HCC,four had diabetes,the prevalence of diabetes in the patients without HCC was 17%(7/42);the level of fasting blood glucose(FBG)((7.3±1.9)mmol/L vs(5.9±1.1)mmol/L)were higher in patients progressed to HCC than those without HCC in DAA treatment group with compensated cirrhosis(x²=7.430 and t=-2.442,respectively,both P=0.019).Conclusions DAA treatment could notably improve liver function and alleviate liver fibrosis,but could not reduce the mortality and incidence of HCC in patients with CHC related cirrhosis significantly.Diabetes and high level FBG may be the risk factors for occurrence of HCC in patients with CHC related compensated cirrhosis.