De Novo Non-Alcoholic Fatty Liver Disease Following Orthotopic Liver Transplantation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition.

Epidemiology and Natural History of Non-Alcoholic Steatohepatitis

“…Onset occurred more frequently in patients with preservation injury on 1-week post-transplantation protocol biopsy. 126,127 Risk factors for recurrent or de novo NAFLD identified in cross-sectional, post-transplantation studies include obesity, diabetes mellitus/insulin resistance, decreased HDL-cholesterol, elevated total cholesterol, and hypertension. These risk factors are present more frequently in post-transplant patients than in the general population, at least in part because of the use of corticosteroids and calcineurin inhibitor-based immunosuppression.…”

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

“…Steatosis in the donor liver has also been identified as a risk factor for the development of steatosis in late post-transplant biopsies, although the mechanism for this is uncertain [121]. Several studies have identified cases of NAFLD, which appear to have arisen de novo following liver transplantation [119,[121][122][123][124][125][126]. However, some of these have occurred in patients who were transplanted for cryptogenic cirrhosis and/or had risk factors for the metabolic syndrome prior to transplantation and could thus be regarded as having recurrent rather than de novo disease [119,122,123,125,127].…”

Nonalcoholic fatty liver disease and liver transplantation

“…Interestingly, the 4 cases showed moderately severe preservation injury on protocol liver biopsy performed at day 7‐8 post‐OLT. As discussed by the authors,84 preservation injury induces some abnormalities that may lead to NAFLD including mitochondrial dysfunction,85 oxidative stress, and lipid peroxidation 86…”