Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease

Table 1 Overview of important studies concerning the management of metabolic dysfunction-associated fatty liver disease/non-alcoholic steatohepatitis patients

	Ref.	Study design	No. of patients	Liver disease	Main findings
Diet/physical exercise	Berzigotti et al[57], 2017	Prospective, uncontrolled	60 (50 completed the study)	Cirrhosis, BMI ≥ 26 kg/m2, portal hypertension	Moderate exercise was safe in patients with compensated cirrhosis
					Diet and moderate exercise reduced body weight and portal pressure
					Weight loss ≥ 10% is associated with more pronounced portal pressure reduction
	Wong et al[55], 2018	Randomized controlled trial	154	NAFLD	Regular exercise associated with significantly more frequent remission of NAFLD (assessed by proton-magnetic MR-spectroscopy)
					NAFLD remission in 67% of non-overweight patients (baseline BMI < 25 kg/m2) with lifestyle intervention
Dyslipidemia	Unger et al[150], 2019	Retrospective	1265	CLD	34.2% of non-advanced and 48.2% of advanced CLD patients did not receive guideline-conform statin therapy
					Guideline-conform statin use was associated with improved overall survival in compensated, but not in decompensated CLD patients
	Abraldes et al[69], 2009	Randomized controlled trial	59	Cirrhosis and portal hypertension	Simvastatin reduced portal pressure (-8.3) in both patients, who did and did not also receive beta-blockers
					Simvastatin improved liver perfusion
					The effects of simvastatin were additive to beta-adrenergic blockade
	Nelson et al[72], 2009	Randomized controlled trial	16	NASH	Simvastatin reduced low-density lipoprotein by 26%
					Simvastatin was well-tolerated
					Simvastatin did not histologically improve NASH (but small sample size, only n = 10 follow-up biopsies)
T2DM	Lavine et al[108], 2011	Randomized controlled trial	173	NAFLD	Sustained ALT level reduction was similar in the metformin and placebo group
					Metformin did not change the NAFLD activity score
	Cusi et al[102], 2016	Randomized controlled trial	101	NASH and prediabetes/T2DM	Significantly more patients receiving pioglitazone (59%) resolved NASH compared to placebo (23%)
					Pioglitazone improved fibrosis score (-0.9 vs placebo 0.0)
					Pioglitazone improved insulin sensitivity in liver, muscle and adipose tissue
	Armstrong et al[104], 2016	Randomized controlled trial	52	NASH	Significantly more patients receiving liraglutide (39%) resolved NASH compared to placebo (9%)
					Significantly less patients receiving liraglutide (9%) exhibited fibrosis progression compared to placebo (36%)
					Liraglutide was safe and well-tolerated
Bariatric surgery	Lassailly et al[114], 2015	Prospective	109	NASH	NASH was resolved in 85% of patients one year after surgery and even in 94% with mild NASH before surgery (assessed via biopsy)
					NASH persistence was higher in patients after gastric banding (30.4%) compared to gastric bypass (7.6%)
	Goossens et al[117], 2016	Retrospective	59	NASH	NASH is an independent predictor of overall mortality after bariatric surgery
					NASH may reduce the overall survival benefit of bariatric surgery
	Eilenberg et al[118], 2018	Retrospective	10	NAFLD/NASH	Liver dysfunction, liver steatosis/fibrosis and cirrhosis may occur after bariatric surgery
					Lengthening of the alimentary or common limb may lead to a clinical improvement in these patients
Post-LT	Krasnoff et al[151], 2006	Randomized controlled trial	151	Post-LT	Exercise and dietary counseling intervention improved exercise capacity and self-reported general health
					Adherence to the intervention was associated with positive trends in exercise capacity and body composition (% body fat)
	Zamora-Valdes et al[152], 2018	Prospective	29	NAFLD/NASH/obese ACLD	Patients, who received sleeve gastrectomy at the time of LT had more pronounced and sustained weight loss
					They also had a lower prevalences of hepatic steatosis, hypertension and insulin resistance 3 yr after LT
	Patel et al[139], 2019	Retrospective	495	Post-LT	Statins were underused after LT (54.3% of patients with known coronary artery disease did not receive statin therapy)
					Statin use was well-tolerated
					Statin therapy was associated with improved overall survival

BMI: Body mass index; NAFLD: Non-alcoholic fatty liver disease; CLD: Chronic liver disease; NASH: Non-alcoholic steatohepatitis; ALT: Alanine aminotransferase; T2DM: Type 2 diabetes mellitus; LT: Liver transplantation; ACLD: Advanced chronic liver disease.