Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

Abstract

Approximately 20% to 30% of patients undergoing liver transplantation for autoimmune hepatitis (AIH) develop features of recurrent disease. Diagnostic criteria for recurrent AIH are similar to those used in the nontransplanted liver and include, in varying combinations, biochemical, serological, and histological abnormalities and steroid dependency. However, these criteria are more difficult to apply in the liver allograft because of potential interactions between recurrent AIH and other complications of liver transplantation, particularly rejection, and the uncertain effects of long-term immunosuppression. In the absence of other reliable diagnostic markers, a number of studies have used the histological finding of chronic hepatitis as the main or sole criterion for diagnosing recurrent AIH. However, this also lacks diagnostic specificity because there are many other possible causes of chronic hepatitis in the liver allograft. In addition, approximately 20% to 40% of biopsies performed on patients as part of routine annual review have histological features of chronic hepatitis, for which no definite cause can be identified. Risk factors that have been associated with the development of recurrent AIH include suboptimal immunosuppression, HLA phenotype, disease type and severity in the native liver, and duration of follow up. In many cases in which recurrent AIH seems to be related to underimmunosuppression, biochemical and histological features rapidly resolve once adequate immunosuppression is restored. However, in other cases, recurrent AIH behaves more aggressively, with progression to cirrhosis and graft failure. Areas that require further study include developing uniform criteria for the diagnosis of recurrent AIH, identifying risk factors for severe recurrent disease, and determining optimal levels of immunosuppression that minimize the impact of disease recurrence without exposing patients to the risks of overimmunosuppression. (Liver Transpl 2001;7:285-291.) R ecurrence of autoimmune hepatitis (AIH) after liver transplantation has been reported in several studies. [1][2][3][4][5][6][7][8][9][10][11][12] The reported rate of recurrence ranges from 11% to 83%, with 20% to 30% documented in most studies. Occasional studies have failed to find evidence of recurrent AIH. 13 There is considerable variation in the criteria used to diagnose recurrent AIH and the reported outcome of disease recurrence, and risk factors for recurrent AIH are also poorly understood. The study by Gonzalez-Koch et al, 14 which appears in this edition of Liver Transplantation, provides further evidence that AIH recurs after liver transplantation, but also highlights some problems that exist in diagnosing disease recurrence in the liver allograft. Diagnostic CriteriaThe main problem with establishing a diagnosis of AIH is the lack of a single specific diagnostic marker. In the native liver, AIH is diagnosed on the basis of a constellation of findings, including the presence of positive features that support a diagnosis of AIH and the a...

Response to steroids in de novo autoimmune hepatitis after liver transplantation

“…The limitations of the classical AIH score has also been noted in the diagnosis of recurrent AIH after LTX, where the possibility of a modified score has been recently suggested. 11,12 This is particularly evident for patients with HCV recurrence. However, HCV patients reported in this article had the most striking histological features, and all of them had a severe clinical presentation.…”

“…We studied HLA class I and II polymorphism by standard complement-dependent microcytotoxicity assays and/or by PCR with sequence-specific primers for the following antigens/alleles: A (1,2,3,11,23,24,25,26,29,30,31,32,33,34,66,68,69,80), B (7,8,13,18,27,35,37,38,39,41,42,44,45,47,48,49,50,51,52,53,55,56,57,58,60,61,62,63,64,65,67,70,73), Cw (1,2,3,4,…”

Liver biopsy interpretation for causes of late liver allograft dysfunction

“…Fewer blastic lymphocytes, slightly greater interface activity, less venous subendothelial inflammation, and slightly more lobular activity cause biopsies with LAR to resemble chronic hepatitis. 4,57 LAR can also present as isolated perivenular inflammation and hepatocyte dropout (so-called "central perivenulitis") [58][59][60] and evolve into typical chronic rejection with ductopenia. 61 Subendothelial inflammation of portal or central veins is not a required finding in such cases.…”

“…76 A similar prevalence has been observed in the pediatric population, in which recurrent native disease is less of a problem; the frequency of "idiopathic" chronic hepatitis was 20% at 1 year of age, rising to 60% at 10 years of age. 77 Cases presenting as central perivenulitis probably represent centrilobular-based acute rejection, or AIH if autoantibodies are also present, 57 because allograft dysfunction usually responds to increased immunosuppression. [59][60][61]78 Some idiopathic posttransplantation hepatitis cases may represent rejection with chronic hepatitic features.…”

Is there such a thing as protocol immunosuppression in liver transplantation?

“…Recurrence of autoimmune hepatitis may be reduced with CS as part of the long-term IS protocol [24]. There is also evidence that recurrence of primary biliary cirrhosis is reduced on long-term cyclosporine rather than tacrolimus [25].…”