Liver transplantation for autoimmune hepatitis: A long-term pathologic study

Abstract

Autoimmune hepatitis (AIH) after liver transplantation (LT) may recur and is difficult to diagnose. Our aims were to define the histopathology of and factors related to AIH recurrence. Fourteen of 475 patients received LT for AIH; 2 died perioperatively. Liver specimens (native and post-LT biopsies) from 12 other patients were reviewed and correlated with pre-and post-LT clinical course and outcome. Recurrent AIH was seen in 5 of 12 patients, 35 to 280 days post-LT as lobular hepatitis with acidophil bodies and lymphoplasmacytic infiltrate. Portal/interface hepatitis was seen with disease progression and 2 of 5 patients developed cirrhosis. Of 7 nonrecurrent patients, 1 had acquired hepatitis C with lobular/portal hepatitis and none developed cirrhosis. Histology suggestive of overlap syndrome was seen in 3 of 12 native livers with no effect on post-LT course or pathology. High-grade necroinflammation was present in native livers at LT in 5 of 5 cases with recurrent AIH and in 1 of 7 without recurrence (P < .01). Pre-LT disease duration, donor/recipient gender distribution, HLA studies, and rejection episodes did not correlate with AIH recurrence. We conclude that (1) recurrent AIH is not uncommon and was seen in 42% of patients with lymphoplasmacytic lobular, portal, and interface hepatitis; (2) acidophil bodies with lymphoplasmacytic cells are seen in early recurrent AIH; (3) recurrent AIH appears at variable time periods post-LT, and the progression is slow; and (4) high-grade inflammation in native liver at LT is a strong predictor of recurrent AIH. (HEPATOLOGY 2000;32:185-192.)

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.…”

“…Titers Ն1:160 are unlikely to be nonspecific background reactivities and therefore compel a thorough evaluation for AIH. 70 Initial manifestations include lobular hepatitis with hepatocyte rosetting 40 that usually evolves into the chronic phase characterized by lymphoplasmacytic portal inflammation with prominent interface activity. Plasmacytic infiltrates characterize AIH, but are not diagnostic requisites.…”

Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation

“…Ayata et al 40 also retrospectively reviewed patients who underwent transplantation for AIH. Recurrent disease (lobular hepatitis, acidophil bodies, lymphoplasmacytic infiltrates, and interface hepatitis) was present in 5 of 12 patients (42%) at 35 to 280 days after transplantation; cirrhosis developed in 2 of 5 patients.…”

Recurrent autoimmune hepatitis after orthotopic liver transplantation

“…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][6][7][8][9][10][11][12][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.…”

“…1,2 Despite these successes, recurrent disease is possible, 2,3,[5][6][7][8][9][10][11][12][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.…”