ReviewAutoimmune Hepatitis After Liver Transplantation
Section snippets
Recurrence of Autoimmune Hepatitis
AIH accounts for 2%–3% of pediatric and 4%–6% of adult LTs performed in Europe and the United States.3 LTs are performed on patients with AIH who present with fulminant hepatic failure, on the 10%–15% who progress to end-stage chronic liver disease despite immunosuppressive treatment, and on those with hepatocellular carcinoma who meet transplant criteria.2, 11 A combination of prednisolone and a calcineurin inhibitor is the most common immunosuppressive regimen used after LT3; outcomes are
Autoantibodies
Patients who received liver transplants for non-autoimmune liver diseases can develop autoantibodies.10, 42 Antinuclear antibodies (ANAs) are most frequently reported, followed by anti–smooth muscle antibodies (SMAs). An atypical form of the liver-kidney microsomal antibody type-1 (LKM-1) has also been detected in these patients; this antibody has been reported to react with an unidentified cytosolic antigen instead of the microsomal liver fraction that contains cytochrome P4502D6, the target
De Novo Autoimmune Hepatitis
Post-transplant de novo AIH was initially described in 1998 among patients who received liver transplants for disorders other than AIH (Table 3). In the first report, during a 5-year period, 4% of 180 children who underwent LT developed a form of graft dysfunction with features identical to those of classic AIH, including hypergammaglobulinemia; positive test results for ANA, SMA, a gastric parietal cell antibody, and atypical LKM-1; and histologic features of chronic hepatitis, with portal and
Pathogenic Mechanisms
Although little is known about the pathogenesis of de novo AIH, the mechanisms of recurrence of AIH after LT are understood (Figure 2). The transplant recipient's immune system is sensitized to species-specific antigens and has a pool of memory T cells that are restimulated and re-expanded when antigens (and autoantigens) are presented, either by the recipient's antigen-presenting cells (APCs), which repopulate the grafted liver, or by the donor's APCs, which share histocompatibility antigens
Conclusions
Although LT is a successful treatment for end-stage liver disease caused by AIH, primary disease recurs in about 30% of patients. Awareness of its existence and appropriate management have reduced the frequency and improved outcomes of AIH. It is important to be cautious in reducing dose of immunosuppressive therapy in patients who received LT for AIH because discontinuation of corticosteroid is a risk factor for recurrent disease. AIH can arise de novo in patients who received LT for disorders
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2018, Journal of AutoimmunityCitation Excerpt :Vento and colleagues reported that a nurse, with a predisposing haplotype, caring for a patient who had hepatitis C virus infection developed clinical features consistent with AIH type 2 after getting infected with HCV herself secondary to a needle stick injury, demonstrating a temporal relationship between hepatitis C and development of AIH [42]. The pathogenesis of post-liver transplantation de novo autoimmunity and in particular of de novo AIH remains to be elucidated and several non-mutually exclusive mechanisms have been invoked [43] and illustrated in Fig. 2. One obvious possibility is that autoantigens are released from damaged tissue during reperfusion inciting an autoimmune response; another possible mechanism is molecular mimicry, whereby exposure to micro-organisms sharing amino acid sequences with autoantigens leads to cross-reactive immunity [44].
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Conflicts of interest The authors disclose no conflicts.
Funding Rodrigo Liberal is supported by a Doctoral Grant from Fundação para a Ciência e Tecnologia, Lisbon, Portugal (reference SFRH/BD/65007/2009). Maria Serena Longhi is supported by a Clinician Scientist Fellowship from the Medical Research Council, UK. Charlotte R. Grant is supported by an Alex Mowat, PhD Studentship (King's College Hospital Charity). Giorgina Mieli-Vergani is supported by WellChild, Cheltenham, and the Children's Liver Disease Foundation, Birmingham, UK. The sponsors had no role in the design or writing of the paper.