Recurrent autoimmune hepatitis after orthotopic liver transplantation

Abstract

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 ؎ 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 ؎ 0.9 years of observation. Five-year patient (86% v 82%; P ‫؍‬ .9) and graft (86% v 67%; P ‫؍‬ .5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v 40%; P ‫؍‬ .008) and healthy subjects (100% v 49%; P ‫؍‬ .01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. L iver transplantation is effective in the treatment of decompensated autoimmune hepatitis. Five-year patient and graft survival rates range from 83% to 92%, 1,2 and the actuarial 10-year survival rate after transplantation is 75%. 3,4 Furthermore, autoantibodies and hypergammaglobulinemia disappear in most patients within 2 years. 1,2 Despite these successes, recurrent disease is possible, 2,3,5-13 and recent reports have indicated that it may lead to cirrhosis and graft failure. 2,8,12 Furthermore, the immunoreactive propensity of the recipient may contribute to greater frequencies of acute rejection, steroid-resistant rejection, and chronic rejection, especially if corticosteroids are withdrawn in the posttransplantation period. [12][13][14][15] The reasons for recurrent disease are unclear, but associations have been made with corticosteroid withdrawal, 5,9,11,16 implantation of an HLA-DR3-negative liver into a HLA-DR3-positive recipient, 5,6,17 immunosuppressive regimens based on tacrolimus, 8,10,12 and pediatric propensities for aggressive disease. 8 However, findings in various centers have been discrepant regarding the prevalence of recurrence, its consequences, and its risk factors. The importance of HLA-DR3 mismatching between donor and recipient 3,5,6,11,12,13 and the impact of corticosteroid withdrawal on the recurrence of autoimmune hepatitis 5,9,14,18 are now disputed. Optimal results after transplantation require clarification of factors contributing to recurre...

Response to steroids in de novo autoimmune hepatitis after liver transplantation

“…[41][42][43] An increased relative risk for type 1 AIH in patients with HLA DR3 and DR4 has been described. HLA DR3 patients experience higher rates of treatment failure, relapse, referral to LTX, and recurrent AIH after LTX, 44 whereas HLA DR4 is associated with a better disease behavior. 45,46 We have also found a significant increase in the prevalence of DR3 in de novo AIH patients, as well as a trend to higher frequencies for B8.…”

“…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

“…Criteria used to distinguish rejection from AIH can be melded into generalized criteria applicable to other causes of late liver allograft dysfunction, [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] including: (1) histopathological evidence of liver injury showing a pattern compatible with the diagnosis (liver tests are usually elevated in a pattern consistent with the diagnosis); (2) positive serological, molecular biological, immunological, or radiographic evidence of pathogen or possible cause of injury; and (3) other causes of similar histopathological changes and elevated liver tests, if present, have been reasonably excluded. Table 1 shows approximate incidences, risk factors, and clinical, immunological, and radiological observations for common causes of late dysfunction.…”

Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management

“…The diagnostic utility of autoantibody testing in the liver allograft is uncertain. Autoantibodies have been found in some patients transplanted for conditions other than AIH (discussed further later), whereas others have histological features compatible with AIH in the absence of demonstrable autoantibodies [179]. In some cases, histological features suggestive of recurrent AIH can precede recurrence of clinical and biochemical symptoms by several years [176].…”