International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation

Abstract

Nonalcoholic steatohepatitis (NASH)-related cirrhosis has become one of the most common indications for liver transplantation (LT), particularly in candidates over the age of 65 years. Typically, NASH candidates have concurrent obesity, metabolic and cardiovascular risks, which directly impact patient evaluation and selection, waitlist morbidity and mortality and eventually posttransplant outcomes. The purpose of these guidelines is to highlight specific features commonly observed in NASH candidates and strategies to optimize pretransplant evaluation and waitlist survival. More specifically, the working group addressed the following clinically-relevant questions providing recommendations based on the GRADE system supported by rigorous systematic reviews and consensus: (1) Is the outcome after LT similar to that of other etiologies of liver disease? (2) Is the natural history of NASH-related cirrhosis different from other etiologies of end-stage liver disease? (3) How should cardiovascular risk be assessed in the candidate for LT? Should the assessment differ from that done in other etiologies? (4) How should comorbidities (hypertension, diabetes, dyslipidemia, obesity, renal dysfunction, etc.) be treated in the candidate for LT? Should treatment and monitoring of these comorbidities differ from that applied in other etiologies? (5) What are the therapeutic strategies recommended to improve the cardiovascular and nutritional status of a NASH patient in the waiting list for LT? (6) Is there any circumstance where obesity should contraindicate LT? (7) What is the optimal time for bariatric surgery: before, during, or after LT? and (8) Donor steatosis: how much relevant is it for LT in NASH patients.

Appraisal of Cardiac Ejection Fraction With Liver Disease Severity: Implication in Post–Liver Transplantation Mortality

“…In liver transplantation (LT), the pretransplant assessment of cardiac risk remains uncertain and clinically challenging; however, recognizing LT patient with cardiac dysfunction is essential because it is associated with serious cardiovascular events, eventually increasing mortality and risk of graft failure …”

“…Consequently, the optimal LVEF thresholds predictive, if any, of early and late mortality are incompletely defined in patients with decompensated liver disease. (9)(10)(11) In liver transplantation (LT), the pretransplant assessment of cardiac risk remains uncertain and clinically challenging; however, recognizing LT patient with cardiac dysfunction is essential because it is associated with serious cardiovascular events, eventually increasing mortality (12,13) and risk of graft failure. (14)(15)(16) In the current study, considering that left ventricle (LV) systolic function is enhanced and vascular tone is reduced in patients with LC, we hypothesized that a higher LVEF cutoff may be predictive of mortality and graft failure in LT patients with decompensated liver disease than in those with compensated liver disease.…”

Peculiarities of Cirrhosis due to Nonalcoholic Steatohepatitis (NASH)

“…Invasive investigations such as coronary angiography may be warranted on a case-by-case basis in patients with abnormal noninvasive assessments. Several centers perform coronary angiography as a primary investigation in transplant assessment, 79 but studies using this strategy are generally retrospective in nature and may be subject to selection bias. The aim of cardiac assessment is to diagnose patients with severe coronary artery disease that clearly precludes transplantation.…”

“…81 Therefore, patients with BMI > 40 kg/m 2 with comorbidities, particularly concurrent diabetes, should undergo careful assessment by a multidisciplinary transplant team with expertise in transplanting patients with morbid obesity. 79 The optimal timing for bariatric surgery (at the time of transplant or deferred) is still unknown, but should not be considered in patients with NASH cirrhosis who have clinically significant portal hypertension prior to transplantation.…”

Predicting Outcomes of Liver Transplantation in Patients With Nonalcoholic Steatohepatitis: Pretransplant Renal Function Is Key

“…Thus, several strategies should be taken to reduce the incidence of CKD and cardiovascular mortality in LT recipients with NASH and pretransplant renal dysfunction. These should include delayed introduction of calcineurin inhibitors (CNIs), a CNI‐sparing regimen, tight control of blood pressure, blood glucose (in those with diabetes), and dyslipidemia, as well as lifestyle interventions to promote weight loss and healthy diet, while the role of bariatric surgery deserves further investigation …”