Metabolic associated fatty liver disease: Addressing a new era in liver transplantation

Table 1 Approach to metabolic associated fatty liver disease in the transplant candidate

Management stage	Challenges	Considerations	Approach
Pre-transplant	Cardiovascular disease	Most common cause of death in MAFLD patients; Older patients with multiple comorbidities driving cardiovascular risk, disease may be subclinical; Pharmacologic optimisation of risk factors can be limited by liver dysfunction e.g., statins, beta blockade, anti-platelets agents	Rigorous pre-transplant assessment including stress echocardiography and coronary angiography in high risk patients; Risk factor modification as per general population
	T2DM	Pre-LT diabetes associated with reduced survival post-LT; Poor glycemic control immediately pre-LT and peri- LT increases surgical complications	Tight glycemic control during waitlist period and peri-operative; Multidisciplinary approach to diabetic management
	Renal dysfunction	Multifactorial in MAFLD, with hypertension and T2DM; Even mild disease at time of LT associated with higher risk of all-cause and cardiovascular mortality	Prevent even small deterioration in renal function prior to LT; Consider simultaneous liver kidney transplant where indicated
	Nutrition	Pre-LT nutrition has major influence on post-LT morbidity, mortality and hospital stay; Assessment is difficult in obese patients and those with ascites; Sarcopenic obesity and myosteatosis are common. Risk factors for long term mortality	Specialist nutritional consultation prior to transplant with assessment for sarcopenia; High energy, high protein diet with enteral feeding if required
Peri-operative	Obesity	More common in MAFLD than other etiologies; Peri-operative challenges e.g., surgical technique, wound infection and dehiscence, biliary complications; Balancing healthy weight loss in pre-LT period with muscle loss and sarcopenia; Exercise often limited by frailty and possible transient increases in portal pressure with excessive strain	Controlled weight loss in pre-LT period ensuring protein requirements met. Very low-calorie diets not recommendedBariatric surgery pre-LT or simultaneously with LT in highly selected patients. Sleeve gastrectomy preferred over laparoscopic banding or gastric bypass
	Donor steatosis	Donor steatosis > 30% is a risk factor for primary graft non-function and graft loss; Balancing risk of complications with steatotic donors against organ availability and demand	Assessment of hepatic steatosis at all stages of organ procurement; Future possibilities with machine perfusion and liver reconditioning
	Cardiovascular risk	NASH patients more likely to have cardiovascular events in the post-operative period	Careful pre-operative assessment to predict risk; Close perioperative monitoring
Post-transplant	Recurrent MAFLD	Due to non-dynamic genetic, metabolic and behavioural factors, 50% of MAFLD transplant recipients have recurrent MAFLD post-LT	Choice of less diabetogenic immunosuppression regimen e.g., steroid free protocols, CNI sparing; Lifestyle and behavioural modification and traditional risk factor modifications e.g., hyperlipidemia, hypertension as per general population
	De novo MAFLD	Contributors to new MAFLD post-LT include diabetogenic medications e.g., CNI, steroids, obesity related to steroids, inactivity and return of appetite	As above

MAFLD: Metabolic associated fatty Liver disease; LT: Liver transplant; T2DM: Type 2 diabetes mellitus; CNI: Calcineurin inhibitor.