Autoimmune liver disease, autoimmunity and liver transplantation

Abstract

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT.

Long-term outcome of liver transplantation in HCV/HIV coinfected haemophilia patients

“…An increased incidence of autoantibody formation, despite adjunctive immunosuppressive treatment, has been reported in patients who received OLT for autoimmune and non-autoimmune liver disease (15,16).…”

Liver transplantation and autoimmune hepatitis

“…Diagnostic criteria of recurrent autoimmune hepatitis (34)(35)(36) -Liver transplantation for confirmed diagnosis of autoimmune hepatitis -Elevated transaminases -Hyper-gammaglobulinemia (elevation of IgG) -Presence of autoantibodies (ANA, SMA and/or Anti-LKM1) -Compatible histopathology(interface hepatitis, portal inflammation and/or lymphoplasmacytic inflammatory infiltrates) -Response to corticosteroid -Exclusion of differential diagnostic considerations impact of rejection for recurrent AIH is not certain (5,32). Interestingly it is suggested that acute (fulminant) AIH is less likely to recur than chronic presentation following LT (5).…”

“…Importantly, there have been several publications regarding de novo hepatitis during or after interferon-based anti-HCV treatment for recurrent hepatitis C posttransplantation (67)(68)(69). However, its pathophysiology is still uncertain, and it is still controversial whether de novo AIH represents a specific type of rejection or a form of have reported recurrent AIH posttransplantation (8,32), since the first report by Neuberger et al in 1984 (33). However, there are no specific biomarkers to diagnose recurrent AIH.…”

The Comparison between HBV Transgenic Mice and Normal Mice after Being Injected Concanavalin A (Con A)

“…Nowadays, chronic hepatitis B, as a major hidden danger [1], is a threaten to human being's health, but there is a lock of effective measures and radical solutions to cure it [2,3]. This situation has an inseparable relationship with the persistent infection of HBV and the relative lag of the research of pathogenic molecular mechanism and the development and evaluation of antiviral drug, on account of the short of the susceptible cell models and animal models to HBV [4,5].…”