S5E-1. Liver transplant pathology: causes of late allograft dysfunction

Most problematic liver allograft biopsies are obtained more than year after transplantation, due largely to overlapping clinical, serological and histopathological features of native disease recurrence and other potential causes of late allograft dysfunction. More than one insult can be responsible. About 75% of biopsies from long-surviving recipients with abnormal liver function tests/symptoms show significant histopathological abnormalities. Native disease recurrence can be categorized as follows: (i) infections (viral hepatitis B, C, D), (ii) dysregulated immunity {autoimmune hepatitis, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and sarcoidosis}, (iii) malignancies, (iv) toxic causes (e.g. alcohol, adverse drug reactions), (v) metabolic disorders, including nonalcoholic steatohepatitis, and (vi) others. The most common and problematic causes of late allograft dysfunction include late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures associated with preservation injury/prolonged ischaemia time, recurrent PBC and PSC, and idiopathic post-transplantation hepatitis. Differential diagnostic challenges include (i) rejection versus chronic hepatitis, (ii) chronic rejection, (iii) biliary strictures versus acute and chronic rejection, (iv) acute and chronic rejection versus PBC, (v) central perivenulitis, (vi) various causes of chronic hepatitis, and (vii) cholestatic or biliary disease versus chronic hepatitis. Practical problems and approach to allograft biopsy interpretation are discussed. Clinicopathological correlation with review of all previous allograft biopsies and close communication with the hepatology team are mandatory. One should be cognizant of the preand post-tranplantation significance of laboratory test results, and the possible alteration of histopathological features by immunosuppressive therapy. Occasionally, rendering a definitive diagnosis may not be possible. However, exclusion of a differential diagnosis may facilitate further therapeutic decisions.