J Korean Soc Transplant.  2013 Dec;27(4):153-159. 10.4285/jkstn.2013.27.4.153.

Histopathological Features of Late Liver Allograft Dysfunction

• Yu E

• KMID: 1841123
• DOI: http://doi.org/10.4285/jkstn.2013.27.4.153

Abstract

Interpretation of late allograft biopsies can be challenging because of overlapping clinicopathological features, regional difference of underlying liver diseases for liver transplantation, and continuous changing of preoperative treatment modalities of native liver diseases. In this review article, the potential causes and histopathological features of late allograft dysfunction are discussed. The causes include recurrence of native liver disease, late-onset acute rejection, chronic rejection, and posttransplant malignancy or hepatitis of unknown etiology. Differential diagnosis between recurrent or late-onset acute rejection and early-stage chronic rejection, either reversible or finally leading to late-stage chronic rejection, is practically difficult; however, clinically, it affects patient treatment. Diagnosis of recurrent hepatitis B virus/hepatitis C virus hepatitis should be made with consideration of both serological evaluation for deoxyribonucleic acid, ribo nucleic acid, or antibodies and histopathological features. Although differentiation of recurrent or de novo autoimmune hepatitis from acute rejection is difficult, patients with autoimmune hepatitis undergo similar treatment. In pediatric patients, evaluation of Epstein-Barr virus-associated changes, which vary from nonspecific hepatitis to post- transplant lymphoproliferative disorder with or without acute rejection, is practically important from the point of treatment. From our 16-year experience in Asan Medical Center, it has become clear that the histopathological diagnosis of late allograft biopsies must be made on the basis of consensus criteria for the common and problematic causes of late complications of liver transplantations proposed by the Banff Working Group, by integration of clinical features and results of key serological tests, and even by consideration of responses to previous treatment.

Keyword

Liver transplantation; Graft rejection; Hepatitis; Recurrence

MeSH Terms

Antibodies
Biopsy
Chungcheongnam-do
Consensus
Diagnosis
Diagnosis, Differential
DNA
Graft Rejection
Hepatitis
Hepatitis B
Hepatitis, Autoimmune
Humans
Liver Diseases
Liver Transplantation
Liver*
Lymphoproliferative Disorders
Recurrence
Serologic Tests
Transplantation, Homologous*
Viruses
Antibodies
DNA

Figure

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  Fig. 1. A representative case of severe late acute cellular rejection. (A) The liver allograft biopsy shows multifocal central perivenulitis and moderate portal inflammation (HE stain, ×12.5). (B) Portal inflammation and bile duct injury is mild (arrow), compared with central perivenulitis (HE stain, ×100). Abbreviations: P, portal tract; CV, central vein.

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  Fig. 2. A representative case of early chronic rejection. (A) The liver allograft biopsy shows minimal portal inflammation with sen-escence of bile duct epithelium (arrow) (HE stain, ×200) and (B) aggregation of foamy histiocytes obstructing the sinusoids (HE stain, ×400).

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  Fig. 3. A representative case of late chronic rejection. The liver allograft biopsy shows diffuse loss of interlobular bile ducts by CK7 immunostaining (A, x12.5) and advanced fibrosis by Masson’ s trichrome staining (B, ×12.5).

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  Fig. 4. A representative case of EBV infection in a pediatric liver transplantation patient. (A) The liver allograft biopsy shows diffuse sinusoidal lymphocytosis (HE stain, x200) and (B) mild lobular activity (HE stain, x200). Abbreviation: EBV, Epstein-Barr virus.

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  Fig. 5. A representative case of de novo autoimmune hepatitis in a pediatric liver transplantation patient. (A) The liver allogfraft biopsy shows moderate mononuclear cell infiltration in the portal tract (HE stain, x100) and (B) bile duct damage by CK7 immunostaining (×400).

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  Fig. 6. Summary of histopathological features of late liver allograft dysfunction and the most probable pathological diagnoses. Abbreviations: PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; PTLD, posttransplant lymphoproliferative disorder.

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