Browsing School of Medicine by Author "Emmanuel, Benjamin"
The Distribution of Change over Time in Metabolic, Inflammatory, and Immune Parameters in HCV-monoinfected and HIV/HCV-coinfected Patients Cured of Hepatitis C Virus by Direct-Acting Antiviral TherapyEmmanuel, Benjamin; Kottilil, Shyamasundaran (2018)Background: Clearance of Hepatitis C virus (HCV) results in rapid changes in metabolic, inflammatory, and immune parameters early in direct-acting antiviral (DAA) therapy. However, the long-term changes beyond sustained virologic response (SVR) and the difference by HIV-coinfection status is unknown. Objective: To investigate the distribution of change, pre-DAA therapy to post-SVR, in metabolic, inflammatory, and immune parameters among chronic Hepatitis C (CHC) patients in an urban population. Methods: CHC patients from four clinical trials who achieved SVR with DAA therapy were analyzed for metabolic parameters (low- and high- density lipoprotein [LDL and HDL], triglycerides, hemoglobin A1C [HbA1C]), inflammatory parameters (alanine and aspirate aminotransferase [ALT and AST]), and cellular immune activation markers (CD4+, CD8+, CD4+:CD8+ ratio, activated CD4+ and CD8+ [HLA-DR+ and CD38+ co-expression] T-lymphocytes. A general linear model for repeated measurements at pre-DAA, DAA, end of treatment, SVR, and post-SVR (year 1-4) was conducted to estimate the mean outcome. Results: A total of 269 CHC patients, 194 HCV and 75 HIV/HCV, achieved SVR. Mean LDL increased from pre-DAA to DAA (86.6 to 107.3 mg/dL, P<0.001), then decreased until post-SVR year 2 (95.5 mg/dL, P<0.001). Mean triglycerides decreased between pre-DAA and DAA (126.2to 111.7 mg/dL, P=0.01), while HDL and HbA1C did not change. Mean ALT and AST normalized rapidly between pre-DAA and DAA (ALT 70.0 to 28.8 U/L, P<0.0001; AST 60.0 to 26.3 U/L, P<0.0001), while ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. At pre-DAA therapy, HCV patients had a significantly higher CD4+ and CD4+:CD8+ T-cells ratio and significantly lower CD8+ and activated CD4+ and CD8+ T-cells compared to HIV/HCV patients. HCV and HIV/HCV patients had significant mean decrease in activated CD4+ and CD8+ T-cells from pre-DAA to post-SVR year 2, while HCV patients had significant mean increase in CD4+ and CD8+ T-cells. Conclusion: CHC patients who achieved SVR with DAA therapy had continued improvements of metabolic (LDL after DAA therapy only and triglycerides), inflammatory (ALT and AST) and T-lymphocytes parameters during DAA therapy and beyond SVR. Thus, decline in immune activation may lead to reduced hepatic inflammation and functional improvement in lipids.