Benedetta Terziroli Beretta-Piccoli1, Claudia Di Bartolomeo2, Gaia Deleonardi3, Ana Gabriela Grondona3, Tania Silvestri3, Cinzia Tesei3, Laura Melidona3, Andreas Cerny4, Joachim Mertens5, Nasser Semmo6, David Semela7, Darius Moradpour8, Giorgina Mieli-Vergani9, Diego Vergani10, Luigi Muratori11. 1. Epatocentro Ticino, Lugano, Switzerland; Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK. Electronic address: benedetta.terziroli@hin.ch. 2. Fondazione Epatocentro Ticino, Lugano, Switzerland. 3. LUM Autoimmunity and Allergy AUSL Bologna, Italy. 4. Epatocentro Ticino, Lugano, Switzerland. 5. Gastroenterology und Hepatology, University Hospital Zürich, Switzerland. 6. Department of BioMedical Research, Hepatology, Inselspital, University of Bern, Switzerland. 7. Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, Switzerland. 8. Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 9. Paediatric Liver, GI and Nutrition Centre, MowatLabs, King's College Hospital, London, UK. 10. Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK. 11. DIMEC, University of Bologna, Bologna, Italy.
Abstract
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is associated with a wide range of immunopathological manifestations, which are significantly improved by successful interferon-based treatment. There is paucity of data on the impact of interferon-free HCV clearance on immunopathological manifestations, which might be expected to disappear more frequently as compared to what reported in interferon-induced HCV-clearance. We have investigated liver autoimmune serology before and after interferon-free clearance of HCV by treatment with direct acting antiviral agents (DAA). METHOD: Patients within the Swiss Hepatitis C Cohort Study who underwent successful (SVR 12) HCV treatment with DAA were tested for autoimmune liver serology according to dedicated guidelines before and at least 6 months after end of treatment. RESULTS: A total of 235 patients were included; 62% males; median age 56 years; 27% with cirrhosis. Median time between end of DAA treatment and post-treatment serum sampling was 17 months. At least one autoantibody before treatment was found in 175 (74%) patients ; 32 (14%) were positive for 2 autoantibodies; no patient was positive for anti-SLA, anti-LC1 or typical AMA before or after DAA. ANA disappeared in 34%, SMA in 52% and anti-LKM1 in one of two patients after successful treatment, but, unexpectedly, one or more autoantibodies appeared in 27% of pre-treatment negative subjects. CONCLUSION: HCV clearance by DAA is associated with autoantibody disappearance in more than one third of the patients who were positive before treatment. However, the majority of the patients remain autoantibody-positive and 27% of those who were negative before treatment developed autoantibodies after DAA-induced HCV clearance. These data confirm that HCV infection is associated with autoimmunity and show that the autoimmune imprint persists after viral clearance by DAA, suggesting that long-term follow-up may be warranted.
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is associated with a wide range of immunopathological manifestations, which are significantly improved by successful interferon-based treatment. There is paucity of data on the impact of interferon-free HCV clearance on immunopathological manifestations, which might be expected to disappear more frequently as compared to what reported in interferon-induced HCV-clearance. We have investigated liver autoimmune serology before and after interferon-free clearance of HCV by treatment with direct acting antiviral agents (DAA). METHOD:Patients within the Swiss Hepatitis C Cohort Study who underwent successful (SVR 12) HCV treatment with DAA were tested for autoimmune liver serology according to dedicated guidelines before and at least 6 months after end of treatment. RESULTS: A total of 235 patients were included; 62% males; median age 56 years; 27% with cirrhosis. Median time between end of DAA treatment and post-treatment serum sampling was 17 months. At least one autoantibody before treatment was found in 175 (74%) patients ; 32 (14%) were positive for 2 autoantibodies; no patient was positive for anti-SLA, anti-LC1 or typical AMA before or after DAA. ANA disappeared in 34%, SMA in 52% and anti-LKM1 in one of two patients after successful treatment, but, unexpectedly, one or more autoantibodies appeared in 27% of pre-treatment negative subjects. CONCLUSION:HCV clearance by DAA is associated with autoantibody disappearance in more than one third of the patients who were positive before treatment. However, the majority of the patients remain autoantibody-positive and 27% of those who were negative before treatment developed autoantibodies after DAA-induced HCV clearance. These data confirm that HCV infection is associated with autoimmunity and show that the autoimmune imprint persists after viral clearance by DAA, suggesting that long-term follow-up may be warranted.