Approach to prevention of non-alcoholic fatty liver disease after liver transplantation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease and non-alcoholic steatohepatitis (NASH) related cirrhosis is third common indication for liver transplantation (LT). Patients who have NASH related cirrhosis and are candidates for LT often have multiple comorbidities.These comorbidities need to be addressed before and after transplantation as it affects overall survival. Like hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis which recurs after transplantation, NASH also recurs after transplant however the impact of the recurrence on allograft and patient outcomes is unclear. Limited data suggests that it does not affect graft and patient survival. De novo NAFLD which is defined as occurrence of fatty liver in a patient who did not have fatty liver prior to LT can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Obesity, hyperlipidemia, diabetes as well as steroid dose and duration after LT are common predictors of recurrence of NAFLD after transplantation.Studies on prevention and treatment of NASH in post-transplant patients are lacking. Prevention of weight gain, regular exercises, weight reducing surgery, limited steroid use or steroid free regimen have been tried with varying success. Future studies for the prevention of NAFLD/NASH are required especially in post liver transplant patient.

Current aspects of renal dysfunction after liver transplantation

“…The development of post-LT metabolic syndrome is frequent[ 56 ]. In addition to lingering pre-LT risk factors, there is an increase in post-LT risks due to immunosuppression with corticosteroids and CNI[ 57 ]. Moreover, it is expected that metabolic syndrome components after LT will continue to rise due to the increase of NASH/MAFLD as an indication for LT[ 31 - 33 , 58 ].…”

De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation

“…Hepatic steatosis has been recognized as the hepatic manifestation of metabolic syndrome (MetS). LT resolves the complications of cirrhosis due to metabolic-associated steatohepatitis (MASH), but the metabolic risks persist and often can get aggravated by exposure to immunosuppressive therapy after LT[ 13 ]. Therefore, it is not surprising to expect a higher rate of recurrent graft steatosis after LT compared to that of de novo graft steatosis due to the underlying MetS and IR that initially led to cirrhosis[ 14 ].…”

“…The development of graft steatosis after LT is related to different factors: Recipient, environmental, genetic, and immunosuppressive factors[ 13 ]. A retrospective study by El Altrache et al [ 18 ] reported the association of recurrent graft steatosis with the occurrence of metabolic abnormalities after LT.…”

“…Increased circulating free fatty acids from the above-mentioned process further promote inflammation and endoplasmic reticulum stress, which aggravates IR more, leading to a vicious cycle[ 22 ]. The immunosuppressive regimen used after LT also plays a critical role in MetS as corticosteroids decrease peripheral glucose absorption, increase hepatic glucose production, and therefore increases the risk of developing post-LT diabetes[ 13 ]. Calcineurin inhibitors (CNIs) that are often used as a part of immunosuppressive therapy also are diabetogenic in nature[ 23 ].…”

“…Dumortier et al [ 17 ] reported steatosis in donors as an important predictor of de novo NAFLD, and therefore the interaction between donor and recipient genetics may also affect disease recurrence[ 13 ]. Previous genomic studies have reported genetic variation in the patatin-like phospholipase domain as conferring susceptibility for the risk of fibrosis and steatosis[ 27 ].…”