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hepatocytic rejection

Monday 26 October 2009

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

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

- Heterogeneous inflammatory changes in liver graft recipients with normal biochemistry. Gelson W, Hoare M, Unitt E, Palmer C, Gibbs P, Coleman N, Davies S, Alexander GJ. Transplantation. 2010 Mar 27;89(6):739-48. PMID: 20134396

- Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation. Adeyi O, Fischer SE, Guindi M. J Clin Pathol. 2010 Jan;63(1):47-74. PMID: 19847014

- What does the long-term liver allograft look like for the pediatric recipient? Hübscher S. Liver Transpl. 2009 Nov;15 Suppl 2:S19-24. PMID: 19877293

- 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

- 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.

- Hernandez H, Kovarik P, Whitington P, Alonso E. Autoimmune hepatitis as a late complication of liver transplantation. J Pediatr Gastroenterol Nutr 2001; 32: 131-136.

- Kerkar N, Hadzic N, Davies E, Portmann B, Donaldson P, Rela M, et al. De-novo autoimmune hepatitis after liver transplantation. Lancet 1998; 351: 409-413.

- 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.

- Hernandez H, Kovarik P, Whitington P, Alonso E. Autoimmune hepatitis as a late complication of liver transplantation. J Pediatr Gastroenterol Nutr 2001; 32: 131-136.

- Heneghan M, Portmann B, Norris S, Williams R, Muiesan P, Rela M, et al. Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults. Hepatology 2001; 34: 464-470.

- Vergani D, Mieli-Vergani G. Autoimmunity after liver transplantation. Hepatology 2002; 36: 271-276.

- Quaglia A, Del Vecchio Blanco G, Greaves R, Burroughs A, Dhillon A. Development of ductopaenic liver allograft rejection includes a hepatitic phase prior to duct loss. J Hepatol 2000; 33: 773-880.

- De novo autoimmune hepatitis following liver transplantation: a case report. Di Cocco P, Barletta A, Clemente K, D’Angelo M, Greco S, Mazzotta C, Orlando G, Rizza V, Famulari A, Grimaldi A, Pisani F. Transplant Proc. 2008 Jul-Aug;40(6):2073-4. PMID: 18675134

- 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]

- Plasma cell hepatitis in liver allografts: Variant of rejection or autoimmune hepatitis? Demetris AJ, Sebagh M. Liver Transpl. 2008 Jun;14(6):750-5. PMID: 18508366 [Free Article]

- Central perivenulitis: a common and potentially important finding in late posttransplant liver biopsies. Hübscher SG. Liver Transpl. 2008 May;14(5):596-600. PMID: 18433067 [Free Article]

- The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers. Krasinskas AM, Demetris AJ, Poterucha JJ, Abraham SC. Liver Transpl. 2008 May;14(5):625-32. PMID: 18433038

- 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]