Abstract: Objective The aim of this clinical trial was to investigate the virological response to direct acting antivirals (DAAs) in patients with chronic hepatitis C (CHC) and liver fibrosis. Methods 65 patients with CHC were encountered in our hospital between June 2019 and January 2022, all patients underwent liver biopsies at presentation, and the combination of sofosbuvir and ribavirin was given to 37 patients and the combination of sofosbuvir and daratavir was given to 28 patients, both lasting for 12 weeks. All the patients were followed-up for 24 weeks. The aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4) were obtained, and the liver stiffness measurement (LSM) was measured by FibroScan. The peripheral blood lymphocyte subsets was determined by FCM. Results The liver histopathological examination showed that ≤F2 liver fibrosis in 31 cases and ≥F3 liver fibrosis in 34 cases in our series; at admission, there were significant differences as respect to the ages [54(35, 62) year old vs. 60(51, 67) year old], LSM [8.1(6.5, 9.0)kPa vs. 17.0(13.1, 26.4)kPa], APRI[ 0.4(0.3, 0.7) vs. 0.9(0.6, 1.4)], FIB-4[ 1.6(0.9, 2.5) vs. 3.7(2.4, 5.2)], PLT counts [174(123, 217)×10⁹/L vs. 130(93, 147)×10⁹/L] and AST levels [76(56, 79)U/L vs. 62(47, 67)U/L, all P<0.05] between patients with ≤F2 and ≥F3 liver fibrosis; at the end of 24 week follow-up, the sustained virologic response (SVR) was 100.0% in the 65 patients with CHC; at baseline, the end of treatment and end of follow-up, the percentages of peripheral blood CD4⁺ cells [(34.6±2.8)%, (41.4±3.4)% and (44.8±3.7)%] and the ratio of CD4⁺/CD8⁺ cells [(1.1±0.2), (1.3±0.3) and (1.6±0.4)] in patients with ≤F2 liver fibrosis were not significantly different compared to [(34.3±3.0)%, (39.6±3.8)% and (41.8±3.7)%] and [(1.1±0.3), (1.4±0.3) and (1.6±0.4)] in patients with ≥F3 liver fibrosis, although they both increased as the prolongation of the antiviral treatment. Conclusion The application of DAAs in the treatment of patients with CHC and different stage of liver fibrosis is efficacious, which not only by the direct antiviral action, but by the modulation of immune functions.

Key words: Hepatitis C, Direct acting antivirals, Sustained virological response, Liver fibrosis, Therapy