摘要
目的探讨应用直接抗病毒药物(DAAs)成功清除丙型肝炎病毒(HCV)后慢性丙型肝炎(CHC)患者肝纤维化程度的改善。方法共纳入111例经DAAs治疗后获得持续病毒学应答(SVR)的CHC患者,比较患者治疗前后白细胞(WBC)、红细胞(RBC)、血小板(PLT)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBil)、血尿素氮(BUN)、血肌酐(Cr)、肝硬度(LSM)、AST和血小板比率指数(APRI)和Fib-4评分(Fib-4 score)的变化;将患者按应用DAAs治疗前的诊断进行分组,其中慢性肝炎组77例,代偿期肝硬化组13例,失代偿期肝硬化组21例,比较各组患者DAAs治疗前后LSM、APRI和Fib-4评分的变化;采用Logistic二元回归分析性别、基因型、体重指数(BMI)、WBC、PLT、ALT、AST、TBil、APRI和Fib-4评分的基线值对LSM变化值的影响。结果入组111例患者,WBC、PLT升高,ALT、AST和TBil降低,与治疗前差异均有统计学意义(Z=-3.842、P<0.001,Z=-3.854、P<0.001,Z=-8.919、P<0.001,Z=-8.882、P<0.001,Z=-4.487、P<0.001),而入组111例患者血肌酐(Cr)和血尿素氮(BUN)与治疗前差异均无统计学意义(Z=-0.287、P=0.774,Z=-0.424、P=0.671)。111例患者的3种无创肝纤维化指标,即LSM、APRI和Fib-4下降,与治疗前差异均有统计学意义(Z=-6.955、P<0.001;Z=-8.836、P<0.001;Z=-6.838、P<0.001),其中代偿期肝硬化组、失代偿期肝硬化组患者LSM、APRI和Fib-4下降幅度均较慢性肝炎组显著(LSM:χ^2=13.52、P<0.001,χ^2=34.00、P<0.001;APRI:χ^2=10.84、P<0.001,χ^2=28.38、P<0.001;Fib-4:χ^2=16.83、P<0.001,χ^2=29.36、P<0.001)。代偿期肝硬化组与失代偿期肝硬化组患者LSM、APRI和Fib-4下降幅度差异均无统计学意义(LSM:χ^2=1.08、P=0.58,Fib-4:χ^2=0.84、P=0.66,APRI:χ^2=0.09、P=0.96)。较高ALT基线值[P=0.045,OR(95%CI)=0.918(0.844~0.998)]、AST[P=0.013,OR(95%CI)=0.862(0.767~0.969)]和APRI基线值[P=0.032,OR(95%CI)=0.001(0.000~0.555)]或较低WBC基线值[P=0.019,OR(95%CI)=2.508(1.161~5.421)]患者获得SVR后LSM得到显著改善。结论成功清除CHC患者的HCV可使其肝纤维化显著改善,且肝硬化患者肝纤维化程度改善更为显著。对CHC患者应尽早启动抗病毒治疗,尽早实现SVR可阻滞CHC患者肝脏炎症及肝纤维化进展,从而减少肝硬化失代偿并发症的发生。
Objective To investigate the improvement of liver fibrosis in patients with chronic hepatitis C(CHC)after removal of hepatitis B virus(HCV)by directly acting antivirals(DAAs).Methods Total of 111 CHC patients with sustained virological response(SVR)after treatment with DAAs were enrolled.White blood cell(WBC),red blood cell(RBC),platelets(PLT),and alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),blood urea nitrogen(BUN),creatinine(Cr),liver stiffness measurement(LSM),aspartate transferase/platelets ratio index(APRI)and Fib-4 scores(Fib-4)of patients,before and after treatment respectively.Patients were divided into groups according to the diagnosis before treatment with DAAs,including 77 patients as chronic hepatitis group,13 patients as compensated cirrhosis group,and 21 patients as decompensated cirrhosis group.LSM,APRI and Fib-4 before and after treatment with DAAs in each group were compared,respectively.Logistic binary regression analysis of the effects of baseline values of gender,genotype,body mass index(BMI),WBC,PLT,ALT,AST,TBil,APRI and Fib-4 scores on LSM changes were analyzed by Logistic binary regression.Results Compared with pretherapy,the counts of WBC and PLT were significantly elevated,ALT,AST and TBil were significantly reduced in 111 patients(Z=-3.842,P<0.001;Z=-3.854,P<0.001;Z=-8.919,P<0.001;Z=-8.882,P<0.001;Z=-4.487,P<0.001).There were no significant differences in serum Cr and BUN before and after treatment of the 111 patients(Z=-0.287,P=0.774;Z=-0.424,P=0.671).The three noninvasive liver fibrosis markers LSM,APRI and Fib-4 of 111 patients were significantly different from those before treatment(Z=-6.955,P<0.001;Z=-8.836,P<0.001;Z=-6.838,P<0.001).The three noninvasive liver fibrosis markers were statistically significant of patients in chronic hepatitis group compared with those of compensated liver cirrhosis group and decompensated cirrhosis group(LSM:χ^2=13.52,P<0.001;χ^2=34.00,P<0.001.APRI:χ^2=10.84,P<0.001;χ^2=28.38,P<0.001.Fib-4:χ^2=16.83,P<0.001;χ^2=29.36,P<0.001).But there was no significant difference in the three noninvasive liver fibrosis markers between patients in compensated cirrhosis group and decompensated cirrhosis group(LSM:χ^2=1.08,P=0.58;Fib-4:χ^2=0.84,P=0.66;APRI:χ^2=0.09,P=0.96).Patients with higher ALT[P=0.045,OR(95%CI)=0.918(0.844-0.998)],AST[P=0.013,OR(95%CI)=0.862(0.767-0.969)],APRI[P=0.032,OR(95%CI)=0.001(0.000-0.555)]baseline levels or lower WBC[P=0.019,OR(95%CI)=2.508(1.161-5.421)]baseline level had a significant improvement on LSM after SVR,all with significant differences.Conclusions The degree of liver fibrosis was significantly reduced in patients with CHC whose HCV were successfully removed,and the changes are more significantly in LC patients.Antiviral therapy should be initiated as soon as possible for patients with CHC.Early realization of SVR could block liver inflammation and liver fibrosis for patients with CHC,thus reducing the occurrence and development of cirrhosis decompensation complications.
作者
孙玉洁
贾因棠
Sun Yujie;Jia Yintang(First Clinical Medical College of Shanxi Medical University,Taiyuan 030000,China;Department of Infectious Diseases,First Hospital of Shanxi Medical University,Taiyuan 030000,China)
出处
《中华实验和临床感染病杂志（电子版）》
CAS
2019年第5期414-420,共7页
Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)
