hepatocytic rejection
Digital cases
Case 263 : Cirrhosis of a liver transplant. Hepatocytic rejection
Definition: Hepatocytic rejection or so-called "de novo autoimmune hepatitis" (AIH) is a special type of graft dysfunction, . This term refers to a progressive posttransplant disease associated with chronic active hepatitis at liver biopsy, elevated serum liver enzymes, increased serum immunoglobulin G (IgG) concentrations, and the presence of non-organ-specific autoantibodies.
Localization
periportal hepatocytic rejection
centrilobular hepatocytic rejection
Etiology
Its incidence in pediatric patients is between 2.3% and 5.2%, and its incidence is even lower in adult orthotopic liver transplantation (OLT) recipients.
The etiology and pathogenesis of this chronic disease are not known, but molecular mimicry and autoimmunity have been hypothesized. Others have tried to classify it as a form of late graft dysfunction in the context of chronic rejection.
Inteface hepatitis (IH) is one of the morphological features that reveal ongoing graft dysfunction. It is at the same time a histological hallmark of the newly determined type of graft dysfunction known as de novo AIH, a denomination obviously chosen to emphasize the resemblance to AIH, even though the dysfunction occurs on a transplanted organ and represents an alloimmune phenomenon.
Patients with periportal hepatocytic rejection (or de novo AIH) have been analyzed separately and specific risk factors, such as lymphopenia, autoimmune liver disease before OLT, seronegative fulminant hepatic failure, and post-OLT viral infections, have been recognized.
IH is a frequent finding and occurrs in 24.4% of the patients, and their evolution was characterized by low-level fluctuation of ALT.
More importantly, after a median follow-up of 12 years, 79% of these patients had fibrosis scores > F2 versus only 11% of those without IH.
Furthermore, IH appearing within 1 year post-OLT was associated with retransplantation in 50% and death before retransplantation, cirrhosis, and HCV infection in 16.7% each, but not with the elevation of IgG levels or the presence of autoantibodies.
Patients with IH appearing > 1 year post-OLT, including those with elevated IgG levels or the presence of non-organ-specific autoantibodies, had a less austere evolution: established cirrhosis, retransplantation, or death occurred in 43.5% in all. None of our patients showed all the features of de novo AIH as defined by the International Autoimmune Hepatitis Group.
The incidences of definite de novo AIH of 2.3 to 5.2% is reported in pediatric liver transplant patients from other study groups.
References
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Interface hepatitis is associated with a high incidence of late graft fibrosis in a group of tightly monitored pediatric orthotopic liver transplantation patients. Herzog D, Soglio DB, Fournet JC, Martin S, Marleau D, Alvarez F. Liver Transpl. 2008 Jul;14(7):946-55. PMID: #18581476#
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Gupta P, Hart J, Millis JM, Cronin D, Brady L. De novo hepatitis with autoimmune antibodies and atypical histology: a rare cause of late graft dysfunction after pediatric liver transplantation. Transplantation 2001; 71: 664-668.
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Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus. Fiel MI, Agarwal K, Stanca C, Elhajj N, Kontorinis N, Thung SN, Schiano TD. Liver Transpl. 2008 Jun;14(6):861-71. PMID: #18508382# [Free Article]
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Cirrhosis after orthotopic liver transplantation in the absence of primary disease recurrence. Seyam M, Neuberger JM, Gunson BK, Hübscher SG. Liver Transpl. 2007 Jul;13(7):966-74. PMID: #17370332# [Free Article]