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.

Keywords: CKD, chronic kidney disease; CNI, calcineurin inhibitors; DM, diabetes mellitus; DPP-4, dipeptidyl peptidase-4; ELTR, European Liver Transplant Registry; ESLD, end-stage liver disease; GLP1 RAs, glucagon-like peptide-1 receptor agonists; Graft survival; HCC, hepatocellular carcinoma; HR, hazard ratio; Hypertension; IRR, incidence rate ratio; Immunosuppressant; LT, liver transplant; MAFLD, metabolic dysfunction-associated fatty liver disease; Metabolic complication; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; New-onset diabetes after transplantation; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; OR, odds ratio; Obesity; Patient survival; SGLT2, sodium-glucose co-transporter-2; Solid organ transplantation; UNOS, United Network for Organ Sharing; mTORi, mammalian target of rapamycin inhibitors.

Fig. 1

Cardiac work-up algorithm in the evaluation of patients with non-alcoholic fatty liver disease before liver transplantation.

Fig. 2

Practical dietary advice for patients with non-alcoholic steatohepatitis-related advanced liver disease according to the Mediterranean diet.