NAFLD and liver transplantation: Disease burden, current management and future challenges

Abstract

Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.

Treatments for NAFLD: State of Art

“…NASH-associated cirrhosis is to date among the top three indications for liver transplantation in most high-income countries, with the alarming trajectory to become the most common [ 1 , 2 ]. Outcomes at 1, 3, and 5 years for patients undergoing a liver transplant for NASH-associated cirrhosis are substantially similar to those for other indications [ 50 , 51 , 52 ]. However, the overall mortality in patients with NASH-associated cirrhosis undergoing liver transplant seems to be more frequently associated with the age of the recipient (i.e., >60 years), presence of obesity (i.e., BMI ≥ 30 kg/m 2 ), T2DM, or post-transplant MetS [ 50 , 52 , 53 , 54 ].…”

“…Outcomes at 1, 3, and 5 years for patients undergoing a liver transplant for NASH-associated cirrhosis are substantially similar to those for other indications [ 50 , 51 , 52 ]. However, the overall mortality in patients with NASH-associated cirrhosis undergoing liver transplant seems to be more frequently associated with the age of the recipient (i.e., >60 years), presence of obesity (i.e., BMI ≥ 30 kg/m 2 ), T2DM, or post-transplant MetS [ 50 , 52 , 53 , 54 ]. Recurrence of NAFLD is also common after liver transplantation, ranging from 20% to 40% of cases, depending by the techniques used for the diagnosis [ 50 , 52 , 53 , 54 ].…”

“…However, the overall mortality in patients with NASH-associated cirrhosis undergoing liver transplant seems to be more frequently associated with the age of the recipient (i.e., >60 years), presence of obesity (i.e., BMI ≥ 30 kg/m 2 ), T2DM, or post-transplant MetS [ 50 , 52 , 53 , 54 ]. Recurrence of NAFLD is also common after liver transplantation, ranging from 20% to 40% of cases, depending by the techniques used for the diagnosis [ 50 , 52 , 53 , 54 ]. Risk factors associated with NAFLD recurrence include: (a) post-transplant weight gain, (b) steroid use, (c) presence of MetS, and (d) PNPLA3 rs738409 in the recipient [ 50 , 52 , 53 , 54 ].…”

“…Recurrence of NAFLD is also common after liver transplantation, ranging from 20% to 40% of cases, depending by the techniques used for the diagnosis [ 50 , 52 , 53 , 54 ]. Risk factors associated with NAFLD recurrence include: (a) post-transplant weight gain, (b) steroid use, (c) presence of MetS, and (d) PNPLA3 rs738409 in the recipient [ 50 , 52 , 53 , 54 ]. In addition, approximately 30% of patients transplanted for reasons different from NASH-associated cirrhosis can develop de novo NAFLD, usually within 3 years of the liver transplantation [ 50 , 52 , 53 , 54 ].…”

“…Risk factors associated with NAFLD recurrence include: (a) post-transplant weight gain, (b) steroid use, (c) presence of MetS, and (d) PNPLA3 rs738409 in the recipient [ 50 , 52 , 53 , 54 ]. In addition, approximately 30% of patients transplanted for reasons different from NASH-associated cirrhosis can develop de novo NAFLD, usually within 3 years of the liver transplantation [ 50 , 52 , 53 , 54 ]. Specifically, T2DM, obesity, arterial hypertension, and liver graft steatosis are the most important risk factors for de novo NAFLD [ 50 , 52 , 53 , 54 ].…”