In contrast with other vascularized allografts, chronic liver allograft rejection is uncommon. Over the last two decades, the incidence at 5 years after transplantation has decreased from 15% to 20% in the 1980s to an expected incidence of 3% to 5% in current liver allograft recipients. 1 This is likely attributable to the unique immunologic properties of a liver allograft, better recognition and control of acute and the early phases of chronic rejection (CR), and the remarkable regenerative capabilities of the liver. [2][3][4][5][6][7][8][9][10][11] Nevertheless, CR is still an important cause of late liver allograft dysfunction and failure. [12][13][14][15][16] And from a practical perspective, proper recognition and staging of CR is essential for long-term patient management, because toxic side effects of long-term immunosuppression force clinicians to significantly lower or discontinue immunosuppression. [17][18][19][20] Moreover, given the inevitable decline in kidney and heart allograft structure and function because of CR, study of the relatively low incidence of CR in liver allografts, and the ability of the liver to recover from CR, will likely lead to valuable insights into transplantation immunobiology in general.
In a previous consensus publication by the Banff Working Group, 21 the panel constructed a working schema for grading acute liver allograft rejection, which has subsequently proven to be simple, reliable, clinically relevant and scientifically correct. 22,23 It is used to grade the necroinflammatory activity of acute rejection that is potentially amenable to therapeutic intervention. At the 5th Banff Conference on Allograft Pathology in 1999, the main goal of the liver sessions was to identify the various stages in the evolution of CR, with the specific aim of addressing two main questions: (1) Can histopathologic features be identified at an early stage of CR, which if left untreated, are predictive of progression to graft failure? This has important clinical implications, because such cases may still be potentially reversible with the use of additional immunosuppression; and (2) Can histopathologic features be used to indicate that irreversible graft damage has occurred? This question also has obvious important clinical implications, because such cases are likely to be unresponsive to additional immunosuppression and depending on the complete clinicopathological profile, may require relisting for retransplantation. An important related issue is whether there are atypical patterns of chronic liver allograft rejection, which appear very similar or identical to chronic hepatitis and lead to cirrhosis, in contrast with the more commonly recognized pattern of CR.
Methods
During the two years since the 4th Banff Consensus conference in 1997, investigators from several large programs and the NIDDK liver transplant database, studied various aspects of chronic liver allograft rejection, including clinical and demographic factors 11,24,25 and histopathologic findings associated with the evolution [26][27][28] and/or reversal or progression to allograft failure. 11,27,29 Abstracts of these works [25][26][27][28][29] can be viewed at: http://tpis.upmc.edu/tpis/Banff/1999/ index.html#Subjects and Titles. The findings from these studies were presented and discussed at the 5th Banff Conference. The working formulation and recommendations below, are based on these studies of more than 2,500 liver allograft recipients in more than 7 centers throughout the world, in combination with previous publications on CR and considerable combined clinical and pathological experience of the Banff Panel on Allograft Pathology.
RESULTS
Definition and Relationship to Acute
Rejection. Chronic liver allograft rejection can be defined as an immunologic injury to the allograft, which usually evolves from severe or persistent acute rejection and results in potentially irreversible damage Abbreviations: CR, chronic rejection; ACR, acute cellular rejection; IPTH, idiopathic post-transplant hepatitis.