Banff 2001 Liver Group Discussions

1. Rejection 2.Centrilobular (zone 3) inflammatory lesions 3.Changes in late post-transplant biopsies Banff Liver Group Discussions

Banff MeetingConsensus Agreement 1995Banff Schema for grading acute liver allograft rejection 1997Problems with diagnosis of chronic rejection 1999Banff Schema for staging chronic liver allograft rejection 2001No further modifications required Banff 2001 presentation M SebaghTest of 1999 Banff Schema for chronic rejection Banff Schema for Grading and Staging LiverAllograft Rejection

DefinitionInflammatory lesions involving hepatic venules and surrounding liver parenchyma ProblemsDetermining aetiology Terminology Centrilobular Inflammatory Lesions

Most cases related to rejection - co-exist with typical portal inflammatory changes - hepatic venular endothelial inflammation often prominent - prognostic importance Banff 2001 presentations Animal model (AJ Demetris) - dendritic cells in walls of hepatic venules likely to be important in pathogenesis Clinical Studies (A Krasinska) - importance in paediatric allograft recipients Centrilobular Inflammatory Lesions Aetiology (1) - Early post-transplant

Diagnosis less straightforward - typical portal inflammatory changes may not be present - hepatic venular endothelial inflammation rarely prominent - other possible causes recurrent disease (viral or autoimmune) acquired “autoimmune” hepatitis drug toxicity cause unknown Banff 2001 presentations - causes discussed Y Nakazawa & A Clouston- acquired “autoimmune” hepatitis D Neil- drug toxicity S Hubscher- recurrent HCV infection Centrilobular Inflammatory Lesions Aetiology (2) - Late post-transplant

Current Term“Central venulitis” BUT (1) Many cases lack hepatic venular endothelial inflammation (2) “Central venulitis” implies a rejection-related process Alternative Term“Central perivenulitis” Centrilobular Inflammatory Lesions Terminology

General Aspects Most diseases leading to transplantation in adults have the potential to recur. Clinical impact of disease recurrence varies widely. Diagnostic Problems Similarity between recurrent disease and other graft complications e.g HCV and acute rejection PBC and chronic rejection PSC and ischaemic cholangitis Disease modification by immunosuppression e.g.Atypical patterns in recurrent HBV & HCV Assessment of Late Post-Transplant Biopsies Disease Recurrence

Banff 2001 Presentations C BellamyAlcoholic liver disease S HubscherHepatitis C U KhettryPrimary biliary cirrhosis M ReynesEvaluation of 10 year post-transplant biopsies Assessment of Late Post-Transplant Biopsies Disease Recurrence

Histological Features Predominantly portal inflammation, variable interface hepatitis Parenchymal inflammation commonly present (may include zone 3 lesions with confluent necrosis) Possible causes Viral Infection (HBV, HCV)recurrent or acquired Autoimmune liver diseaserecurrent or acquired Drug toxicity Rejection Banff 2001 presentations J Hart, A Sonzogni- de novo “autoimmune” hepatitis in paediatric allograft recipients Assessment of Late Post-Transplant Biopsies Other Findings - Unexplained Chronic Allograft Hepatitis

1.Rejection no modification to existing Banff Schema needed 2.Centrilobular inflammatory lesions (“Central Perivenulitis”) consensus document with guidelines for histological assessment and differential diagnosis 3.Changes in late post-transplant biopsies (“Chronic Allograft Hepatitis”) consensus document with guidelines for histological assessment and differential diagnosis of unexplained chronic hepatitis Banff Liver Group Discussions Summary and Further Plans