How is fatty liver disease (MASLD) treated?

In the past, fatty liver was referred to as NAFLD (Non-Alcoholic Fatty Liver Disease). Today, international scientific societies have adopted a new definition and classification.

“Since 2023, the condition has been termed MASLD (Metabolic dysfunction-associated steatotic liver disease). The reference to metabolic dysfunction highlights the direct link between steatotic liver disease and systemic metabolic disturbances.

According to the most recent EASL–EASD–EASO guidelines, MASLD is diagnosed when hepatic steatosis is present:

• in the absence of excessive alcohol intake,
• and associated with at least one metabolic risk factor such as overweight/obesity, type 2 diabetes, hypertension, dyslipidemia (low HDL cholesterol and high triglycerides), or insulin resistance.

This definition goes beyond the older, more restrictive concept of NAFLD, allowing earlier identification of at-risk patients, even in cases of moderate alcohol consumption,” explains Dr. Del Poggio.

“Fat accumulates because the liver receives excess energy in the form of fatty acids, which derive from high sugar and fat intake, as in diabetes and obesity. These fatty acids are toxic to the liver, as they oxidize and damage mitochondria the ‘powerhouses’ that generate energy for the cell.

To protect itself, the liver neutralizes and stores fatty acids in the form of triglyceride droplets,” explains Dr. Del Poggio.

MASLD is often a silent condition, producing few and non-specific symptoms in its early stages, such as:

• heaviness or discomfort in the right upper abdomen,
• abdominal bloating,
• fatigue,
• difficulty concentrating.

“Frequently, hepatic steatosis is detected incidentally during an abdominal ultrasound prescribed for other reasons. However, further tests are required to confirm the diagnosis and to establish severity,” notes the hepatologist.

Assessing hepatic fibrosis is crucial, as it reflects the extent of liver damage caused by persistent inflammation. Fibrosis can be evaluated using:

• FIB-4 (Fibrosis-4 Index): a first-level tool based on age, AST, ALT, and platelet count;
• FibroScan or liver elastography: second-level tests that quantify fibrosis more precisely;
• liver biopsy: reserved for complex cases.

Blood tests are also essential to exclude other causes of steatosis and to evaluate both hepatic injury and the extent of metabolic dysfunction.

If left undiagnosed, MASLD can progress to more severe conditions, including:

• Metabolic dysfunction-associated steatohepatitis (MASH): characterized by inflammation and scarring that permanently impair liver function;
• Hepatic fibrosis: progressive formation and accumulation of scar tissue;
• Cirrhosis: advanced liver disease in which healthy tissue is replaced by scar tissue, leading to structural and functional failure;
• Hepatocellular carcinoma (HCC): the most common form of primary liver cancer.

“And the risks of MASLD are not limited to the liver: untreated metabolic risk factors also significantly increase the risk of cardiovascular complications. In fact, for many patients, the cardiovascular risks outweigh the hepatic ones,” warns Dr. Del Poggio.

“To date, the primary therapy for MASLD consists of lifestyle modification, which can reduce hepatic fat and even reverse fibrosis in its early stages,” explains the hepatologist.

Key management strategies include:

• Weight loss: reducing body weight by 7–10% can significantly improve the disease and, in early stages, even achieve remission;
• Regular aerobic exercise: moderate-intensity physical activity, 3–4 times per week for 30 minutes; even daily choices like taking the stairs instead of the elevator help;
• Diet: rich in fruits, vegetables, and fiber, while reducing saturated fats and refined sugars;
• Alcohol reduction or complete abstinence in advanced stages.

Alongside lifestyle interventions, it is crucial to manage metabolic risk factors and comorbidities with specific therapies.

Some medications used for other conditions also provide hepatic benefits:

• ACE inhibitors and ARBs (for hypertension) can slow fibrosis progression;
• Statins, vital for lowering cholesterol and cardiovascular risk, may also protect the liver;
• Certain antidiabetic agents (SGLT2 inhibitors, GLP-1 receptor agonists) show efficacy in MASLD, though in Italy they are currently reimbursed only for diabetic patients.

For patients with significant fibrosis, a new drug, resmetirom, is already in use in the United States and was recently approved in Europe. It stimulates the hepatic thyroid hormone receptor, increasing energy utilization by the liver. Clinical trials have demonstrated histological improvement in steatohepatitis and fibrosis, with an acceptable safety and tolerability profile.

Other agents, such as vitamin E, metformin, pioglitazone, and silybin, may help protect the liver from oxidative stress and reduce fat accumulation.

“Among new therapeutic perspectives, bariatric surgery is proving highly effective in selected patients, significantly improving MASLD by addressing both metabolic risk factors and hepatic fibrosis,” concludes Dr. Del Poggio.