Metabolic%20dysfunction-associated%20steatotic%20liver%20disease Treatment

• Essential principle of therapy of nonalcoholic fatty liver disease (NAFLD) is to treat underlying cause
• Goals of treatment are to improve insulin resistance and liver enzyme levels and improve histologic features

• Pharmacological therapy is indicated in patients with biopsy-proven progressive nonalcoholic steatohepatitis (NASH) and in those in early stage of NASH with increased risk of progressing to fibrosis (age >50 years, diabetes, metabolic syndrome, increased ALT or active NASH with high necroinflammatory activity)
• Pharmacologic treatments for NAFLD/NASH are targeted at underlying metabolic syndrome-related diseases such as obesity, type 2 diabetes mellitus, dyslipidemia and hypertension as well as liver dysfunction itself

Insulin Sensitizers

Thiazolidinediones (eg Pioglitazone)

• Peroxisome proliferator-activated receptor agonists with insulin-sensitizing effects
• Recommended for patients with insulin resistance
• It was shown in clinical trials that Pioglitazone improves liver histology in patients with biopsy-proven NASH with and without type 2 diabetes mellitus
• Main side effects of Pioglitazone are weight gain, bone fractures in women, and rarely congestive heart failure

Glucagon-like Peptide-1 Analogues (eg Liraglutide)

• Act on glucose-insulin interplay and have shown favorable results in pre-marketing studies on liver enzymes
• A randomized placebo-controlled trial showed daily SC injections of Liraglutide for 48 weeks demonstrated more resolution of steatohepatitis and less fibrosis progression

Dipeptidyl Peptidase-4 Inhibitors (DPP4i) (eg Alogliptin, Linagliptin, Sitagliptin, Vildagliptin)

• A single arm, multicenter, non-randomized study has shown that Alogliptin is a potential new therapeutic strategy for the prevention of NAFLD progression in patients with type 2 diabetes mellitus
• Further studies are needed to conclude the beneficial effects of DPP4i therapy on hepatic enzymes to prevent disease progression in NAFLD patients with type 2 diabetes mellitus

Antioxidants, Cytoprotective and Lipid-lowering Agents

Vitamin E

• A free radical scavenger and a chain-breaking antioxidant in free radical reactions such as lipid peroxidation
• Studies have shown improvement in hepatic biological and histological parameters in non-diabetic patients with biopsy-proven NASH
• Further studies are needed for Vitamin E to be used in cirrhotic or diabetic NASH patients

Statins (eg Ezetimibe and HMG-CoA reductase)

• May be used in patients with NAFLD/NASH and hypercholesterolemia to prevent cardiovascular risk
• In patients already taking statins, it is advised to continue with the medication and only consider stopping when liver enzyme levels double within 3 months of starting statins
• Avoid giving statins in patients with decompensated cirrhosis

Antihypertensives

Angiotensin II Receptor Antagonist (ARB)

• Angiotensin II receptor antagonist is recommended in NASH patients with hypertension
• Inhibits fibroblast activity resulting in inhibition of tissue fibrosis in several organs

Other Agents

Pentoxifylline

• Recommended in patients with NASH
• Considered to have both antioxidant and anti-TNF alpha effects
• Clinical trials and meta-analyses found that Pentoxifylline improved serum biochemical indices and hepatic histological change

Omega-3 Fatty Acids

• May be considered in patients with NAFLD for the treatment of hypertriglyceridemia 

Obeticholic Acid and Elafibranor

• New agents currently undergoing phase 3 registration trials for the treatment of NASH