Poster Presentation Lorne Infection and Immunity 2022

HCV infection induces prolonged inflammation and elevated chronic disease risk biomarkers even after curative direct-acting antiviral treatment (#140)

Salimeh Ebrahimnezhaddarzi 1 , Joseph S Doyle 1 2 , Brendan Harney 1 2 , Rachel Sacks-Davis 1 3 , Irene Boo 1 , Long Nguyen 1 , Paul M Dietze 1 4 , Anthony Jaworowski 1 2 , Heidi Drummer 1 5 6 , Alexander J Thompson 7 , Margaret E Hellard 1 2 3 5 , Anna C Hearps 1 2
  1. Disease Elimination Program , Burnet Institute, Melbourne, VIC, Australia
  2. Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Victoria, Australia
  3. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
  4. National Drug Research Institute, Curtin University, Melbourne, VIC, Australia
  5. Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  6. Department of Microbiology, Monash University, Melbourne, VIC, Australia
  7. Department of Gastroenterology, St Vincent's Hospital and the University of Melbourne, Melbourne, VIC, Australia

Around 58 million people globally have Hepatitis C virus (HCV) with an estimated 1.5 million new infections annually. Untreated chronic infection often leads to liver damage and can increase risk of inflammatory diseases including cardiovascular disease (CVD) and diabetes. We investigated whether HCV-associated inflammation/immune dysfunction persisted following viral clearance by direct-acting antiviral (DAA) treatment.

Plasma samples were collected from people who inject drugs with viremic HCV infection at baseline, and 12 and 48 weeks after DAA therapy (n=32, median age 39 years [range 25-57], 75% male). Control individuals were HCV antigen and antibody negative and of a comparable age and sex (n=29, mean age 40 [range 25-60], 72% male). Levels of soluble biomarkers of inflammation/immune activation and chronic disease risk were measured in plasma samples using Luminex immunoassay (R&D Systems) or commercial ELISA.

Biomarkers of inflammation (IL-6, soluble TNF- receptor II (sTNF-RII), high sensitivity (hs) CRP), endothelial activation (VCAM) and coagulation (d-dimer) were elevated in untreated HCV+ individuals compared to controls (p<0.05 for all variables measured). Levels of the endothelial activation biomarker VCAM were decreased after DAA treatment compared to pre-treatment samples (p=0.003). In contrast, IL-6, d-dimer and hsCRP, which have all been independently associated with increased risk of CVD, as well as sTNF-RII were not significantly altered by viral clearance and remained elevated 48 weeks after DAA treatment in HCV+ people as compared to controls (p>0.05 for all). The blood glucose marker of diabetes risk, HbA1c, was also significantly elevated in HCV+ individuals 48 weeks post-treatment as compared to controls (p<0.001).

This study showed persistent elevation of biomarkers associated with increased risk of CVD and diabetes in HCV+ people despite curative DAA therapy. These findings suggest people who have current or past HCV infection, particularly those who inject drugs, should be closely monitored for CVD and diabetes risk.