Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide. In the last decade it has become the third most common indication for liver transplantation in the United States. Increasing prevalence of NAFLD in the general population also poses a risk to organ donation, as allograft steatosis can be associated with non-function of the graft. Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease, although long term outcomes beyond 10 year are lacking. NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted. De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Predictors for NAFLD post-transplant recurrence include obesity, hyperlipidemia and diabetes as well as steroid dose after liver transplantation. A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk. Although immunosuppression side effects potentiate obesity and the metabolic syndrome, studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population. Based on pre-transplant data, sustained weight loss through diet and exercise is the most effective therapy for NAFLD. Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents. Studies of these therapies are lacking in the post-transplant population. A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Liver transplantation; Metabolic syndrome; Outcomes; Management

Core tip: Non-alcoholic fatty liver disease (NAFLD) is a prevalent indication for liver transplantation. It also poses a risk to organ donation, with decreasing rates of suitable allografts. NAFLD frequently recurs in the allograft or develops de novo. Post-transplant recurrence is related to obesity and immunosuppression associated metabolic derangements. A polymorphism in PNPLA3 also increases recurrence risk. Pre-transplant data favors sustained weight loss through diet and exercise as the most effective therapy for NAFLD. Vitamin E and insulin-sensitizing agents are occasionally used. Trials on immune-suppression regimens in this population are sorely needed. A multimodality approach to treatment should be utilized in management of post-transplant NAFLD.