ABSTRACT
Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)
ABSTRACT
Background: The treatment of high priority populations, including patients actively using intravenous drugs (active PWID), must be prioritized to accomplish the WHO HCV elimination goals by 2030. Simplification of the treatment cascade is key to reaching this goal, even more so in the COVID-19 era Sofosbuvir/velpatasvir (SOF/VEL) is a protease inhibitor-free, pangenotypic, panfibrotic, single duration, single tablet regimen, to be taken without regards to food and with limited drug-drug interactions This real-world analysis evaluates SOF/VEL as a simple strategy to implement a testand- treat approach in HCV-infected active PWID Methods: Adult active PWID treated for HCV with 12 weeks SOF/VEL in different clinical settings were included from 25 cohorts in 6 countries Patients with a history of decompensation or prior NS5A-inhibitor exposure were excluded The endpoints were HCV cure (undetectable HCV RNA ≥12 after the end of therapy, SVR12) and time-to-treatment (TT) between most recent HCV RNA measurement and SOF/VEL treatment start Results: Analysis included 340 patients, mean age 44±10years, 84% male, 15% compensated cirrhotic (CC) and 8% treatment-experienced, with 43% genotype (GT) 1 and 41% GT3 73% of patients were diagnosed with a mental disorder, 27% were homeless and 21% incarcerated Of patients with TT available (n=334), 10% were treated the same day of diagnosis, 16% within 1 week, 39% within 1 month, and 69% within 3 months Treatment adherence below 90% was observed in 24 patients (8%) SVR12 is available for 254 patients (75%), as non-virological or unknown cause of failure was documented in 86 patients (25%), 79% due to lost-to-follow-up (LTFU) SVR12 was 98% overall (249/254), 98% (80/82) in non-cirrhotic and 95% (20/21) in CC patients Active PWID with mental disorders showed 97% SVR12 (181/186) Of active PWID with GT3 infection, 96% (104/180) were cured, including 95% (20/21) of those with CC Of 31 patients starting treatment within 1 week of diagnosis, all achieved SVR12 compared to 126/129 (98%) starting within 3 months of diagnosis Conclusion: SOF/VEL is a simple HCV treatment resulting in high cure rates in active PWID, including patients with multiple complicating factors LTFU remains a challenge in this population The simplicity of the SOF/VEL approach allowing for shortening of the patient care cascade and rapid treatment starts with high cure rates may help address this important issue.