Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults

Abstract

In children, a type of graft dysfunction associated with autoimmune features has been described. We have identified 7 adult liver-transplant (LT) recipients from a series of over 1,000 consecutive transplant recipients who presented between 0.3 years and 7.2 years following transplantation with characteristic symptoms, autoantibody profiles, and histologic findings of autoimmune disease. The indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC), hepatitis C cirrhosis, and cryptogenic cirrhosis. Two patterns of de novo autoantibody development were noted; anti-liver-kidney-microsome (LKM) antibody development at high titer in association with an aspartate transaminase (AST) > 500 and antinuclear ( Long-term follow-up of large numbers of liver-transplant recipients has led to a reasonably clear understanding of the causes of graft dysfunction. Liver-function test abnormalities are most commonly associated with rejection, sepsis, vascular compromise, biliary complications, lymphoproliferative disease, and recurrence of the original disease. In some circumstances, the cause of graft dysfunction may be impossible to ascertain. A recent report described a unique form of graft dysfunction occurring in pediatric liver allograft recipients late after liver transplantation (LT). This form of graft dysfunction occurred in association with serologic and histologic features compatible with autoimmune hepatitis (AIH) in patients who underwent transplantation for etiologies other than AIH. 1 Although graft dysfunction in association with the presence of autoantibodies has been described in adults, 2-4 it has not been characterized. A recent report described 2 patients who underwent transplantation for primary biliary cirrhosis (PBC) who developed an autoimmune-type reaction in their liver allograft. 5 In this report, we describe a characteristic form of graft dysfunction in adults akin to the de novo AIH syndrome described in children, 1 except for a more severe graft dysfunction that may result in graft loss. The entity occurred in a group of liver allograft recipients who underwent transplantation at King's College Hospital for indications other than AIH over a 10-year period. PATIENTS AND METHODSOver a 12-year period of observation (1988-99), 7 adults from a series of more than 1,700 adult LT recipients had a characteristic form of graft dysfunction. The indications for transplantation were Ecstasy-induced acute liver failure, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), PBC, hepatitis C cirrhosis, and cryptogenic cirrhosis. Of these, 4 were male, 3 were female, and all were white. Demographic features are summarized in Table 1. The median age at transplantation was 33.4 years (range, 19-58 years). All 7 patients received cadaveric grafts, and postoperative immunosuppression was achieved with cyclosporine to maintain trough concentrations of 150 to 250 g/L in the first 6 months and 100 to 200 g/L the...

Response to steroids in de novo autoimmune hepatitis after liver transplantation

“…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

“…Patients without AIH before transplantation can develop autoantibodies either as a complication of otherwise typical rejection 11,12,29 or in association with new-onset AIH. [30][31][32][33][34][35][36] "Non-organ-specific" autoantibodies have been detected in up to 71% of patients after liver transplantation, 37 emphasizing the need for clinicopathological correlation.…”

Chronic allograft dysfunction: Diagnosis and management. Is it always progressive?

“…Graft hepatitis was identified in 5% of the series and in 11% of those at low risk of recurrence. Indications for those at low risk included cryptogenic cirrhosis (13), steatohepatitis (12), ␣ 1 -antitrypsin deficiency (3), acetaminophen toxicity (1), neuroendocrine tumor(1), and epithelioid hemangioendothelioma (1). Hepatitis developed between 2 weeks and 6 years after liver transplantation, but in 22 cases, it was identified within the first 8 months.…”

“…There is often a good response to treatment with additional immunosuppression with corticosteroids, but in some cases there is relentless progression to cirrhosis and graft failure. 13 Although the term "de novo AIH" has been used, the term has been debated. It has been argued that de novo AIH is appropriate, since the condition arises de novo and fulfills the criteria for AIH.…”