MASLD

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently defined as the presence of hepatic steatosis (detected by ultrasound in the vast majority of cases) associated with metabolic dysfunction (1 of 5 criteria) without significant alcohol consumption (<140 or <210 g per week in women and men, respectively).

In South America, the current prevalence of MASLD is estimated at 35.7% in the general population and could increase to 68% in high-risk groups (i.e., those with type 2 diabetes mellitus [T2DM] or obesity).

The natural history of MASLD ranges from isolated steatosis to steatohepatitis, liver fibrosis, and cirrhosis. However, particular attention has been paid to metabolic dysfunction-associated steatohepatitis (MASH) and advanced liver fibrosis, as they have been linked to disease progression and mortality, respectively.

Screening for MASLD is not recommended in the general population, as isolated steatosis is not associated with a clinically significant increased risk of liver complications. Screening for MASLD and fibrosis is recommended in people with abnormal liver biochemistry or radiological signs of hepatic steatosis, as well as in those with T2DM or overweight, especially those over 50 years of age. Ultrasonography is the first-line test for screening for hepatic steatosis due to its accessibility and ease of use. Proton density fat fraction (PDFF) obtained by magnetic resonance imaging (MRI) offers a more accurate quantification of liver fat content, and a relative decrease of ≥30% on PDF-MRI is associated with a higher likelihood of histological response and resolution of MASH.

FIB-4 is the biomarker of choice for initial fibrosis risk stratification in clinical practice. It is very easy to access because it is calculated based on the patient's age, transaminases, and platelet count. Patients with indeterminate or high risk based on FIB-4 or their clinical history should undergo a second-step analysis using a technique with greater sensitivity and specificity for determining the stage of liver fibrosis. In Latin America, transient elastography (FibroScan®) is suggested as a secondary technique for risk stratification in patients with MASLD.

The Mediterranean diet should be implemented in all patients with MASLD, regardless of the stage of fibrosis. In patients with overweight or obesity (excess body weight), the recommended weight loss goal is 7% to 10% of total body weight (3% to 5% in lean MASLD), which is associated with improved liver histology.

In adults without cardiovascular or musculoskeletal contraindications, exercise should be recommended, including 150 to 300 minutes per week of moderate-intensity aerobic physical activity, 75 to 150 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity.

In people with MASLD and significant fibrosis (F2), absolute abstinence from alcohol should be recommended. Patients with MASLD who actively smoke should be advised to quit smoking.

The only drug currently approved for the treatment of patients with MASH and significant or advanced fibrosis (F2-3) is resmetirom at doses of 80 mg or 100 mg. Unfortunately, this drug is not currently available in Latin America.

Incretin-based therapies could be considered in people with MASH and overweight or DM, depending on local availability and individual risk assessment of potential side effects.

Other therapies, such as pioglitazone and sodium-glucose cotransporter 2 inhibitors, can be considered on a case-by-case basis, but have not shown significant benefit in the progression of liver fibrosis, the control of which is the primary goal of treatment.

Bariatric surgery should be considered in patients with MASLD and class 2 or 3 obesity, especially in those who have not achieved adequate weight loss or metabolic improvement through lifestyle modifications and anti-obesity medications. However, careful patient selection and a thorough preoperative evaluation are crucial.

Hepatocellular carcinoma (HCC) screening should be performed in all patients with cirrhosis. Patients with advanced fibrosis (F3) may also benefit from screening, so HCC surveillance could be proposed in this subgroup of patients. Likewise, a comprehensive cardiovascular risk assessment should be routinely performed in patients with MASLD.