关键词: 丙型肝炎, 二型糖尿病, 索磷布韦, 维帕他韦, T 淋巴细胞免疫球蛋白黏蛋白 3, 程序性细胞死亡蛋白-1, 治疗

Abstract: Objective The aim of this study was to investigate the antiviral efficacy efficacy and its impact of on peripheral blood mononuclear cell (PBMC) T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and programmed cell death protein 1 (PD-1) expression of sofosbuvir/velpatasvir in the treatment of patients with chronic hepatitis C (CHC) and concomitant diabetes mellitus type 2 (T2DM). Methods 74 patients with CHC and concomitant T2DM were enrolled in our hospital between January 2023 and June 2024, with 37 cases in each group, and were randomly assigned to receive peg-interferon-α and ribavirin treatment for 24 weeks in control, or receive sofosbuvir/velpatasvir orally once daily for 12 weeks in observation group. Serum HCV RNA loads were determined by RT-PCR, fasting plasma glucose (FPG), 2h postprandial blood glucose (2hPG) and glycated hemoglobin (HbAlc) were routinely obtained, and HOMA-IR was calculated. Percentages of PBMC Tim-3 and PD4 positive cells were detected by flow cytometry, and serum liver fibrosis parameters were assayed by chemiluminescent assay. Results Rapid virological response, end of treatment virological response and sustained virological response rates in the observation group were 75.7%, 100.0% and 97.3%, all significantly higher than 13.5%, 73.0% and 67.6%, respectively (P<0.05) in the control; by end of 24 week treatment, serum ALT and AST levels were (32.8±4.5)U/L and (30.6±5.9)U/L, both much lower than [(50.5±19.1)U/L and (46.5±8.2)g/L, respectively, P<0.05] in the control group; there were no significant differences as respect to FPG, 2hPG, HbAlc and HOMA-IR changes between the two group(P>0.05); percentages of peripheral blood TIM-3 CD4, PD-1 CD4 and PD-1 CD8 positive cells in the observation were (1.5±0.3)%, (0.3±0.1)% and (1.4±0.2)%, all much lower than [(1.8±0.2)%, (0.5±0.1)% and (1.6±0.3)%, P<0.05] in the control group; serum hyaluronic acid, procollagen type III N-terminal propeptide and type 4 collagen levels were much lower in the observation as compared to in the control group. Conclusion Application of sofosbuvir and velpatasvir is a satisfactory regimen in the treatment of patients with CHC and concomitant T2DM, which might have an inhibitory effects on TIM-3 and PD-1 expression.

Key words: Hepatitis C, Type 2 diabetes mellitus, Sofosbuvir, Velpatasvir, T cell immunoglobulin domain and mucin domain 3, Programmed cell death protein 1, Therapy