Current views on rejection pathology in liver transplantation

P>Histological assessments continue to play an important role in the diagnosis and management of liver allograft rejection. The changes occurring in acute and chronic rejection are well recognized and liver biopsy remains the 'gold standard' for diagnosing these two conditions. Recent interest has focused on the diagnosis of late cellular rejection, which may have different histological appearances to early acute rejection and instead has features that overlap with so-called 'de novo autoimmune hepatitis' and 'idiopathic post-transplant chronic hepatitis'. There is increasing evidence to suggest that 'central perivenulitis' may be an important manifestation of late rejection, although other causes of centrilobular necro-inflammation need to be considered in the differential diagnosis. There are also important areas of overlap between rejection and recurrent hepatitis C infection and the distinction between these two conditions continues to be a problem in the assessment of liver allograft biopsies. Studies using immunohistochemical staining for C4d as a marker for antibody-mediated damage have found evidence of C4d deposition in liver allograft rejection, but the functional significance of these observations is currently uncertain. This review will focus on these difficult and controversial areas in the pathology of rejection, documenting what is currently known and identifying areas where further clarification is required.