Curative Effect And Long-Term Follow-Up Of Genotype 1 Patients With HCV-Related Compensated Cirrhosis Treated With PR And The Relationship Between Serum IL-35,IL-17 And Disease Progression Of Hepatitis C

?Objective?To study the effect and clinical outcome of antiviral treatment of genotype 1 patients with HCV-related compensated cirrhosis who were treated with pegylated interferon alpha-2a and ribavirin?PR?.To investigate the correlation between serum IL-35,IL-17 and disease progression in patients with chronic hepatitis C.?Methods?1.In our parallel retrospective cohort study,fifty-four genotype 1 patients with HCV-related compensated cirrhosis received PR therapy and symptomatic treatment with colony-stimulating factors.And these patients undertook a long-term clinical follow-up for about five years.The efficacy and recurrence rate of antiviral therapy were evaluated.Transient elastography?TE?was used to detect liver stiffness measurement?LSM?.The occurrence of clinical events?hepatic encephalopathy,ascites,gastrointestinal bleeding,hepatocellular carcinoma and death?was compared in SVR group and NSVR group.2.Thirty-one patients with chronic hepatitis C,twenty-six patients with hepatitis C related liver cirrhosis,eight patents with HCV-related hepatocellular carcinoma and twenty-three normal controls were enrolled in the study.Collected peripheral blood of them.The serum levels of IL-35 and IL-17 were determined by enzyme-linked immunosorbent assay.Subjects in the study accepted blood routine test,liver function test and serum AFP detection.The patient groups accepted HCV geotype detection and HCV viral load detection.Comparison between the two groups was made by t test,and Spearman correlation analysis was used to investigate the association between serum IL-35,IL-17and clinical indexes.?Results?1.Fifty-four genotype 1 patients with HCV-related compensated cirrhosis finished the PR therapy,and thirty-five of them?64.81%?acquired sustained virological response?SVR?.Fifteen out of 23 patients?65.22%?became SVR after the first antiviral course,9/14?64.29%?after the second,8/13?76.92%?after the third,2/3?66.67%?after the forth and 1/1?100%?after the fifth.Only one case relapsed at 30 weeks after course.During the antiviral treatment period,patients'LSM took a turn for the better to varying degrees.The LSM of SVR group had a significant statistical difference?P=0.0004?.During the long-term follow-up after course,the LSM of SVR group got a further decline and kept at a well level.However,there was no improvement on the LSM of NSVR group.The mean duration of follow-up was 60 months.There were three cases got HCC in NSVR group,while none in SVR group.The differences between two groups were significantly for ascites?P=0.0168,RR=0.2353,95%CI 0.0390-1.422?and HCC?P=0.0391,RR=0.0000,95%CI infinity?.2.The serum levels of IL-17 of normal control?NC?group,chronic hepatitis C?CHC?group,liver cirrhosis?LC?group and hepatocellular carcinoma?HC?group were?36.05±13.69?pg/ml,?54.27±21.73?pg/ml,?50.67±20.43?pg/ml and?40.82±16.23?pg/ml,respectively.There were significant differences between CHC group and NC group,as well as LC group and NC group?both P<0.01?.The serum levels of IL-35 of NC group,CHC group,LC group and HC group were?76.96±47.96?pg/ml,?132.9±72.88?pg/ml,?177.2±80.91?pg/ml and?167.00±177.20?pg/ml,respectively.There were significant differences among four groups?all P<0.05?.Spearman correlation analysis showed that the serum level of IL-35 of LC group was positively correlated with TBIL?r=0.44,P=0.03?.The serum levels of IL-35 of CHC group and LC group were positively correlated with the serum levels of IL-17(r_CHC=0.3818,P=0.0410,r_LC=0.4364,P=0.0480).?Conclusions?1.Pegylated interferon alpha-2a and ribavirin can effectively restrain HCV in genotype 1patients with HCV-related compensated cirrhosis.Symptomatic treatment of adverse reactions can improve treatment compliance.Patients who failed in the previous treatment can acquire SVR via repeated treatment or extended course of treatment.Acquisition of SVR can decrease recurrence rate,reduce the occurrence of clinical events,such as liver cancer,and lessen the progression of liver cirrhosis.2.The serum levels of IL-35 of CHC group and LC group were positively correlated with the serum levels of IL-17.In patients with chronic hepatitis C and patients with liver cirrhosis,serum level of IL-35 is positively correlated with serum level of IL-17.In patients with liver cirrhosis,serum level of IL-35 is positively correlated with TBIL.It may be that IL-17 promotes the development of liver cirrhosis.And IL-35 may be one of the important facts which affect the incidence of hepatitis C related hepatocellular carcinoma.