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 Therapy
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AbstractBackground: 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.
DescriptionUniversity of Maryland, Baltimore. Epidemiology and Preventive Medicine. Ph.D. 2018
Keyworddirect-acting antiviral therapy
hepatitis C virus
Hepatitis C, Chronic
Sustained Virologic Response