Clinical Study On DAAs Antiviral Therapy In Patients With Genotype 1b Chronic HCV Infection

Objective:To observe the sustained virological response(SVR)rate after EBR/GZR and LDV/SOF,which have been included in China’s medical insurance list,were used to treat patients with genotype 1b chronic HCV infection.The effects of the two schemes on liver inflammation indexes(ALT,AST,GGT,TBIL),liver fibrosis indexes(LSM,HA,LN,CⅣ,PCⅢ),and serum IL-17,CXCL10 levels were analyzed.The correlation between serum IL-17,CXCL10 and liver inflammation and fibrosis indexes before and after treatment was preliminarily investigated.Methods:A total of 76 cases of newly diagnosed patients with chronic HCV type 1b infection who were treated in the Infectious Diseases Department of 404 Hospital of Mianyang,Sichuan in May,June and July of 2020 were included as the research objects.Collect general information of patients,including gender,age,course of infection,past antiviral history,etc.Collect the baseline and the treatment endpoint(12 weeks after treatment)of clinical data,including serum HCV RNA loads,the liver inflammation indexes(ALT,AST,GGT,TBIL),liver fibrosis indexes(LSM,HA,LN,CⅣ,PCⅢ),B ultrasonic of abdomen,and abdominal CT/MRI.Serum IL-17 and CXCL10levels were detected at baseline and treatment endpoint,respectively.EBR/GZR or LDV/SOF were selected for antiviral therapy according to patients’liver and kidney function,complicated diseases and economic status,and LDV/SOF was selected for combination with ribavirin(RBV)in patients with cirrhosis.According to different treatment regimen,44 cases were divided into EBR/GZR group(57.89%)and 32 cases were LDV/SOF group(42.11%).According to the clinical manifestations,LSM and abdominal B ultrasonic/CT/MRI imaging findings,the patients were divided into group A,with 33 cases(43.42%)without significant liver fibrosis group,group B,with 23 cases(30.26%)liver fibrosis group,group C,with 20 cases(26.32%)in liver cirrhosis group.Analysis of SVR12 incidence,and changes of liver inflammation indexes,liver fibrosis indexes,IL-17,CXCL10 in different groups after antiviral therapy.The correlation between serum IL-17,CXCL10 and liver inflammation indexes and liver fibrosis indexes were analyzed.Results:1.At the treatment endpoint,96.05%(73/76)of 76 patients achieved SVR12.The levels of liver inflammation indexes(ALT,AST,GGT),liver fibrosis indexes(LSM,HA,LN,CⅣ,PCⅢ),and IL-17,CXCL10 levels were all lower than those of the baseline,and the differences were statistically significant(P<0.05).There were no adverse reactions leading to withdrawal.2.At the treatment endpoint,97.73%(43/44)and 93.75%(30/32)patients in the EBR/GZR group and the LDV/SOF group reached SVR12,respectively,but the difference between the two groups was not statistically significant(P=0.569).The levels of liver inflammation,liver fibrosis,IL-17 and CXCL10in the EBR/GZR group and the LDV/SOF group decreased compared with the baseline,with statistical significance(P<0.05),but there was no statistical significance in the decrease range of each index between the two groups(P>0.05).3.At the treatment endpoint,the incidences of SVR12 in group A,group B and group C were 100%(33/33),95.65%(22/23)and 90.00%(18/20),respectively,and the difference was not statistically significant(χ~2=3.128,P=0.104),but as the degree of liver fibrosis increases,the incidence of SVR12has a downward trend.At the baseline of treatment,the liver inflammation indexes(ALT,AST,GGT)and liver fibrosis indexes(HA,LN,CIV,PCIII)in group C were higher than those in group A and group B,and the difference was statistically significant(P<0.05).There was no significant difference between group A and group B(P>0.05).The differences in LSM,IL-17 and CXCL10were statistically significant(P<0.001).Further pairwise comparison showed that group C>group B>group A,and the difference was statistically significant(P<0.05).At the treatment endpoint,the liver inflammation indexes(ALT,AST,GGT),liver fibrosis indexes(LSM,HA,LN,CⅣ、PCⅢ),IL-17 and CXCL10in the three groups were lower than those at the baseline,and the difference was statistically significant(P<0.05).The liver inflammation indexes(ALT,AST,GG),liver fibrosis indexes(LSM,HA,LN,CⅣ、PCⅢ)and IL-17,CXCL10 in group C were the most significantly decreased,and the differences were statistically significant(P<0.05).There was no significant difference between group A and group B(P>0.05).4.At the baseline of treatment,IL-17 was positively correlated with ALT,AST and GGT(r=0.274,P=0.016;r=0.341,P=0.003;r=0.298,P=0.009),which was not correlated with HCV RNA(P>0.05).CXCL10 was positively correlated with AST at baseline(r=0.267,P=0.020),but not with ALT,GGT and HCV RNA(P>0.05).At the treatment endpoint,IL-17 was still positively correlated with ALT,AST and GGT(r=0.247,P=0.031;r=0.258,P=0.024;r=0.284,P=0.013).CXCL10 had no correlation with ALT,AST and GGT(P>0.05).5.At the baseline of treatment,IL-17 was positively correlated with LSM,HA,LN,CⅣand PCⅢ(r=0.698,0.639,0.428,0.539,0.521;P<0.05).CXCL10was positively correlated with LSM,HA,LN,CⅣand PCⅢ(r=0.666,0.529,0.464,0.540,0.488,P<0.05).At the end of treatment,IL-17 and CXCL10 were still positively correlated with LSM,HA,LN,CⅣand PCⅢ(P<0.05).Conclusion:1.Under the current medical insurance policy,the SVR12 rate of patients with genetype 1b chronic HCV infection can reach 96.05%using two DAAS regimens,with fewer adverse reactions and good tolerance.The clinical efficacy of the two regimens is similar.2.IL-17 and CXCL10 were involved in the process of liver inflammation and fibrosis.The expression level of CXCL10 may be more closely related to the severity of liver inflammation.3.Anti-viral treatment with DAAS down-regulated the expression levels of IL-17 and CXCL10,and significantly improved the liver inflammation indexes and liver fibrosis indexes,indicating that anti-viral treatment with DAAS can effectively control the liver inflammation response and liver fibrosis process.4.In different stages of liver disease,with the aggravation of liver fiber degree,the SVR after DAAS resistance to HCV has a decreasing trend.Therefore,in order to achieve better SVR,anti-HCV therapy should be started as early as possible.