Influencing Factors Of Spontaneous Viral Clearance And Fibrosis Progression In Subjects With Hepatitis C Virus Infection

Objective: Hepatitis C virus (HCV) infection is an important global healthproblem with approximately2.2-3%of the world’s population being infected.In China, the prevalence of HCV is approximately3.0%. There are two distinctoutcomes of acute HCV infection: spontaneous viral clearance (occurring inapproximately15-45%of subjects) and progression to chronic infection(55-85%of subjects). In those who develop chronic infections progression tofibrosis, cirrhosis, end stage liver disease and hepatocellular carcinoma canoccur. For the acute hepatitis C virus infection is commonly an asymptomaticand mild illness, the precise infection time is commonly unknown. So thenature history of HCV infection is not fully elucidated. The purpose of thepresent study was to enhance our understanding of the natural history ofhepatitis C infection and identify those variables associated with HCVspontaneous clearance, hepatocyte injury and fibrosis progression afterhepatitis C virus infection.Methods: A total of579HCV-infected subjects were enrolled in ourretrospective study and divided into HCV spontaneously clearance group andchronically HCV-infected group. All subjects were investigated by the unitedquestionnaire. Hepatitis C virus antibody, HCV RNA，liver function, bloodroutine, liver stiffness and SNP of IL28B rs12979860were detected. Univariateanalysis and multivariate analysis were performed to identify those factorsassociated with spontaneous viral clearance, clinical features and fibrosisprogression.Results: A total of92spontaneous HCV clearance subjects and312chronically HCV infected patients were enrolled to analysis the influencing factors of spontaneous viral clearance. In univariate analysis, female gender(P=0.001), a history of icteric hepatitis (P=0.001), co-infection with HBV(P<0.001) and rs12979860CC genotype (P=0.022) were positively associatedwith spontaneous HCV clearance, while long term alcohol consumption(P=0.006) was negatively associated with clearance. In multivariate analysis,female gender (OR=2.42,95%CI:1.23-4.75), a history of icteric hepatitis(OR=3.03,95%CI:1.47-6.25), current HBV co-infection (OR=6.02,95%CI:2.37-15.31) and rs12979860CC genotype (OR=3.23,95%CI:1.09-9.55)remained independent variables associated with spontaneous HCV clearance.The clinical features were compared in92spontaneous HCV clearance subjectsand487chronically HCV infected patients, the abnormal rate of ALT, AST andGGT in chronic hepatitis group was significant higher than that in recoveredgroup (P<0.001). Mean values of blood platelet count in chronic hepatitisgroup was significant lower than that in recovered group (P<0.001). Liverstiffness measurement results indicated fibrosis stage normal (<F2) inrecovered group was significant higher than that in chronic hepatitis group(83.7%vs50.8%, P<0.001). Factors associated with abnormal rate of ALT andAST were analysised among487chronically HCV infected patients. Inunivariate analysis, alcohol consumption and history of icteric hepatitis werepositive associated with ALT and AST abnormal, while female was negativeassociated with ALT and AST abnormal (P<0.05). The patients with1bgenetype HCV infection and HCV RNA<4×105IU/ml were positive associatedwith AST abnormal (P<0.05). After multivariate analysis, only male (OR=3.23,95%CI:1.51-6.91) remained independent variables associated with ALTabnormal, and HCV-RNA1b genotype (OR=2.06,95%CI:1.40-3.05) andHCV RNA<4×105IU/ml (OR=2.28,95%CI:1.50-3.47) remained independentvariables associated with AST abnormal. Factors associated severe liverfibrosis was analysised among484chronically HCV infected patients, only age (OR=1.78,95%CI:1.08-2.94) and current co-infection with HBV (OR=3.13,95%CI:1.12-8.71) remained significant related to severe fibrosis.Conclusion: Spontaneous HCV clearance is more likely to occur in females,subjects with a history of icteric hepatitis, HBV co-infections and those withthe rs12979860CC genotype. The patients of spontaneous viral clearancegroup had better clinical features than those of chronic HCV infection group.Female gender, HCV RNA genotype and HCV RNA<4×105IU/ml wereindependent variables associated ALT/AST abnormal. Severe liver fibrosis ismore likely to occur in patients with older age or current coinfection with HBV.