Liver transplantation and nonalcoholic fatty liver disease.

Abstract

Nonalcoholic fatty liver disease (NAFLD) can manifest as a benign fatty infiltration of the liver or as nonalcoholic steatohepatitis (NASH), with inflammation and fibrosis progression leading to cirrhosis. As soon as patients with cirrhosis decompensate, liver transplantation is the optimal intervention. NASH-related cirrhosis is the third most common indication for transplantation in the current era and accounts for 10% to 13% of transplants performed. 1 NASH-related cirrhosis is the only underlying disease that is increasing in frequency in liver transplant recipients in comparison with other diseases, including hepatitis C and alcohol-related liver disease. 1 These data depict patients identified with NASH as the primary or secondary cause of cirrhosis in the Scientific Registry of Transplant Recipients and likely underestimate the number of patients with a secondary cause of NASH because most patients are identified by only 1 cause of disease. It is projected that NASH will usurp hepatitis C as the most common cause of liver disease in the transplant population in the coming years. Patients with NASH tend to be older and more frequently female with a higher body mass index and metabolic complications (diabetes, hypertension, hyperlipidemia, and cardiovascular disease) before transplantation. 2,3 In comparison with other transplant recipients, patients with NASH who undergo transplantation have a higher likelihood of demonstrating metabolic syndrome and possibly renal failure after transplantation. 4,5 Animal studies 6 have demonstrated increased inflammatory responses to ischemia/reperfusion injury in mice with NASH versus control mice, but human studies have not been performed, and the clinical consequences remain to be determined. Despite all these issues, patients undergoing transplantation for NASH-related cirrhosis have similar graft and patient survival in most studies. 1-3,7-9 However, according to comparisons with patients with other specific underlying diseases, NASH patients may have lower 1- and 3-year survival rates than patients undergoing transplantation for cholestatic disease. 2 NASH patients who undergo transplantation have a higher frequency of infectious 2,3 or cardiovascular causes of death 3,7 and less frequently die of recurrent disease than other patients. Importantly, when patients are analyzed according to higher risk status (defined as age > 60 years and body mass index > 30 kg/m 2 with pretransplant diabetes and hypertension), highrisk NASH patients have a 25% immediate mortality rate and a 50% 1-year mortality rate in comparison with Model for End-Stage Liver Disease score–matched controls. NASH patients not considered high-risk have survival rates similar to those of all other transplant recipients. 2 Both steatosis and steatohepatitis can recur after liver transplantation. The exclusion of alcohol-related disease is still important to consider. In an earlier study of 25 patients undergoing transplantation for NASH or cryptogenic cirrhosis with biopsy after transplantation, 100% demonstrated steatosis within 5 years. 8 In a more recent large, single-center study of 257 patients undergoing transplantation for NASH or cryptogenic cirrhosis, steatosis was demonstrated in 18% of patients undergoing transplantation for NASH within 1 year and in 45% within 5 years. 7 Steatohepatitis, however, was less common and was found in only 7% of NASH recipients by 5 years and in 18% by 10 years in this study. 7 Fibrosis progression to cirrhosis occurred in 5% of NASH recipients over 5 years and in 10% of NASH recipients over 10 years. However, fibrosis progression over 10 years occurred in 30% of the patients in whom NASH developed in the allograft and in 8% to 9% of the patients with simple steatosis or no steatosis in the allograft. 7 In another study, 9 54% of NASH patients with liver biopsies (or 39% of NASH patients who underwent transplantation) at a mean of 11