What is the long-term outcome of the liver allograft?

With improved long-term survival following liver transplantation (LT), issues relating to the assessment of the liver allograft in long-term survivors are becoming increasingly relevant. Histological abnormalities are commonly present in late post-transplant biopsies, including protocol biopsies from patients who appear to be well with good graft function. Recurrent disease is the commonest recognised cause of abnormal graft histology, but may be modified by the effects of immunosuppression or interactions with other graft complications, resulting in complex or atypical changes. Other abnormalities seen in late post-transplant biopsies include rejection (which often has different appearances to those seen in the post-transplant period), de novo disease and a number of changes of uncertain aetiology such as "idiopathic" post-transplant hepatitis (IPTH) and nodular regenerative hyperplasia. In many cases graft dysfunction has more than one cause and liver biopsy may help to identify the predominant cause of graft damage. Problems exist with the terminology used to describe less well understood patterns of graft injury, but there is emerging evidence to suggest that late rejection, de novo autoimmune hepatitis and IPTH may all be part of an overlapping spectrum of immune-mediated injury occurring in the late post-transplant liver allograft. Careful clinico-pathological correlation is very important and the wording of the biopsy report should take into account therapeutic implications, particularly whether changes in immunosuppression may be indicated. This article will provide an overview of the main histological changes occurring in long-term survivors post-LT, focusing on areas where the assessment of late post-transplant biopsies is most relevant clinically.