Hepatitis C virus (HCV) is currently the leading indication worldwide for orthotopic liver transplantation. However, the majority of patients receiving transplant for HCV eventually develop histopathologic evidence of recurrent allograft HCV and approximately 10% die or require retransplantation within the first 5 post-operative years because of accelerated graft injury and cirrhosis. Traditional induction immunosuppressive regimens and intensive immunosuppression used to treat episodes of acute cellular rejection (ACR) are associated with enhanced viral replication and higher likelihood and severity of recurrent HCV. At our institution, therefore, we have used low-dose steroid therapy in an effort to limit HCV replication. However, this practice has been associated with frequent early presentations consistent with ACR. Here, we present three cases consistent with histologic ACR treated with conventional antirejection therapy that improved transiently, but evolved rapidly to progressive HCV. A fourth patient with a similar presentation experienced dramatic improvement in aminotransferases when treated solely with interferon and ribavirin. We propose that histologic characteristics traditionally associated with ACR may, in fact, represent early recurrent HCV as both processes share common immunopathogenetic mechanisms, or alternatively, that both ACR and recurrent HCV may be present simultaneously. We conclude that in cases suggestive of ACR, careful consideration should be given to treatment for recurrent HCV in lieu of or in concert with intensive immunosuppression.
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Immunity
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia. Electronic address:
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.
View Article and Find Full Text PDFJ Viral Hepat
February 2025
Statistics, Modelling and Economics Department, UK Health Security Agency, London, UK.
Chronic hepatitis C virus (HCV) infection is associated with significant morbidity, mortality and health economic burden. Over 90% of HCV cases in England occur in people who inject drugs (PWID). Current treatments for HCV are effective but do not protect against reinfection.
View Article and Find Full Text PDFHarm Reduct J
January 2025
School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
Background: The introduction of Direct-Acting Antivirals (DAAs) transformed Hepatitis C (HCV) treatment, despite this uptake of DAAs remains lower than required to meet the WHO Sustainable Development Goal (3.3). Treatment with interferon was suggested to be able to deliver important outcomes for people who use drugs in addition to a viral cure, such as social redemption, and shift from a stigmatised identity.
View Article and Find Full Text PDFNutrients
December 2024
Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, Victor Babeș Street 8, 400012 Cluj-Napoca, Romania.
Background/objectives: Magnesium plays a crucial role in immune function, influencing immunoglobulin synthesis, antibody-dependent cytolysis, and other immune processes. In renal transplant patients, magnesium deficiency is primarily induced by calcineurin inhibitor treatment, through the reduction of magnesium transporter proteins in the renal tubules, leading to magnesium loss.
Methods: To assess the correlation between serum magnesium levels and the long-term outcomes of renal graft and transplant recipients, we conducted a retrospective study on 87 patients who have had a transplant for more than 5 years, a period considered immunologically stable.
Cureus
December 2024
Diagnostic Radiology, Bolan Medical College Quetta, Quetta, PAK.
Introduction Although metabolic dysfunction-associated fatty liver disease (MAFLD) is becoming more common in individuals with hepatocellular carcinoma (HCC), it is still unknown how this condition relates to postoperative complications of HCC. While hepatitis B/C virus (HBV/HCV) infection and alcohol use are primary risk factors, MAFLD has emerged as a significant contributor to HCC incidence. Understanding the prognostic impact of MAFLD on HCC outcomes, particularly post-radical resection, is essential.
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