Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is poorly understood, but the cellular immune response is likely to have a major role. Daclizumab, an interleukin-2 receptor (IL-2R) antibody that blunts T-cell activation, leading to a decreased risk for cellular rejection, is used frequently in transplant recipients. The aim of this study is to evaluate the effect of daclizumab therapy on the incidence and severity of recurrent HCV. Forty-one liver transplant recipients (21 patients, HCV positive; 20 patients, HCV negative) at high risk for neurological or renal complications of calcineurin inhibitors were administered daclizumab, mycophenolate mofetil (MMF), and steroids in the early post-LT period, followed by tacrolimus and a steroid taper. All patients were followed up prospectively for graft function and disease recurrence with protocol liver biopsies day 7, month 4, and yearly. Compared with patients without HCV, patients with HCV administered daclizumab had greater 4-month serum alkaline phosphatase, total bilirubin, and alanine aminotransferase (ALT) levels. These biochemical differences resolved by 12 months, except for persistent elevation of ALT levels. Compared with a well-matched HCV control population, patients with HCV administered daclizumab were more likely to have an earlier onset of hepatitis, jaundice, and greater histological activity. Recurrent hepatitis progressed more rapidly in the daclizumab group; 45% developed advanced disease within 1 year. HCV viral load in the daclizumab group was significantly greater at both 4 months and 1 year. Results of this study suggest that the use of adjuvant IL-2R antibodies in combination with MMF in the early peritransplantation period may be associated with early recurrence of hepatitis C and more rapid histological progression of disease.
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PMID:Anti-interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. 1175 8

Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25 inhibits effector T cell activation, regulatory T cell expansion and survival, and activation-induced T-cell apoptosis. Because CD25 blockade reduces IL-2 consumption by effector T cells, it increases IL-2 bioavailability allowing for greater interaction with the intermediate-affinity IL-2R, and therefore drives the expansion of CD56bright natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56bright NK cell expansion and DAC HYP efficacy in reducing relapses and MRI evidence of disease activity in patients with RMS in phase II and phase III double-blind, placebo- and active comparator-controlled trials. Therapeutic efficacy was maintained during open-label extension studies. However, treatment was associated with an increased risk of rare adverse events, including cutaneous inflammation, autoimmune hepatitis, central nervous system Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) syndrome, and autoimmune Glial Fibrillary Acidic Protein (GFAP) alpha immunoglobulin-associated encephalitis. As a result, DAC HYP was removed from clinical use in 2018. The lingering importance of DAC is that its use led to a deeper understanding of the underappreciated role of innate immunity in the potential treatment of autoimmune disease.
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PMID:Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strategy for Relapsing Multiple Sclerosis. 3086 55