# Treatment approaches for advanced MASH
Treatment of advanced MASH focuses primarily on slowing or stopping liver fibrosis and reducing liver inflammation. There is no medicine that completely cures the disease, but various approaches can halt or improve liver damage. The choice depends on how far fibrosis has progressed, your metabolic profile (weight, blood sugar, fats) and how your liver responds.
Lifestyle measures
ProveniIncluded in official guidelines, or approved by EMA or FDA
Weight loss and exercise form the basis of any treatment. Studies show that loss of at least 5–10% of your body weight can reduce inflammation and fat storage in the liver. More intensive weight loss (15% or more) can improve fibrosis markers.
- **Weight reduction**: Usually through dietary changes (less fat, less sugar, fewer calories) and sometimes with guidance from a dietitian. How it works: lower body weight is associated with lower insulin resistance and less fat accumulation in and around the liver.
- **Regular exercise**: at least 150 minutes of moderate activity per week has proven effective, even without weight loss. Exercise improves insulin sensitivity and lowers liver inflammation independently of weight.
- **Dietary pattern**: A Mediterranean diet or DASH diet is often recommended. Studies suggest that limiting refined carbohydrates, added sugar and alcohol is beneficial.
In some patients, lifestyle changes alone are not sufficient. Then medicines or, in specific cases, surgery may be considered.
Medicines targeting metabolic factors
GLP-1 receptor agonists
ResearchediPositive results in clinical studies, not yet standard treatment
Medicines such as semaglutide (also known from weight loss) are being studied for MASH because they promote weight loss and reduce insulin resistance. Recent reviews suggest beneficial effects on liver inflammation and in some cases on fibrosis markers.
- **How it works**: These agents reduce food intake, improve glucose control and reduce weight.
- **Known side effects**: Nausea, vomiting, diarrhoea, especially at first. Rare: pancreatitis, kidney problems.
GLP-1 agonists currently have no official recognition in guidelines as a specific MASH treatment, but research is ongoing.
FXR agonists (farnesoid X receptor)
ProveniIncluded in official guidelines, or approved by EMA or FDA
Obeticholic acid (OCA) is the first medicine approved in the US and Europe for MASH. It works on a receptor in liver and gut bacteria involved in bile and fatty acid metabolism.
- **How it works**: OCA reduces liver inflammation and fibrosis formation by restoring a regulatory cycle involving bile. This leads to lower insulin resistance and reduced liver enzyme levels.
- **Known side effects**: Severe itching (in 10–30% of users), elevated cholesterol (managed with statins), liver enzyme fluctuations.
OCA is approved for non-cirrhotic MASH with F2–F3 fibrosis (moderate to severe fibrosis without cirrhosis). Efficacy is modest but demonstrable: approximately 18% of treated patients show improvement in fibrosis grade compared to 9% in the control group.
Medicines targeting liver inflammation and fibrosis attack processes
Pioglitazone (thiazolidinedione)
ResearchediPositive results in clinical studies, not yet standard treatment
This medicine is sometimes prescribed for MASH with insulin resistance, especially if diabetes is present.
- **How it works**: Pioglitazone improves insulin sensitivity in muscle and fat, which secondarily reduces liver inflammation.
- **Known side effects**: Weight gain, fluid retention (risk of heart failure), bone fractures in the long term. These reasons make it unsuitable for all patients.
Pioglitazone is not specifically approved for MASH, but is considered in some centres where insulin resistance is also present.
Experimental approaches under investigation
DGAT2 inhibitors
ExperimentaliOngoing in study setting, outcome still unknown
This substance inhibits an enzyme involved in fat synthesis in the liver. Early studies show reduced liver fat, but the effect on fibrosis formation is still unclear.
- **Current status**: In human trials; no approval yet.
FGF21 analogues and other fibrosis inhibitor candidates
ExperimentaliOngoing in study setting, outcome still unknown
Efruxifermin (an FGF21 mimetic) and other candidates are being actively investigated because they suppress inflammatory genes and can prevent fibroblasts from forming connective tissue.
- **Current status**: Multiple phase II/III trials ongoing; results not yet completed.
microRNA and noncoding RNA-based therapies
ExperimentaliOngoing in study setting, outcome still unknown
Studies point to a role of certain microRNAs (such as miR149) in fibrosis inhibition by bringing fibroblasts to rest. This is still purely research territory.
- **Current status**: Laboratory and animal studies; no human trials known.
Treatment of hepatic decompensation and advanced cirrhosis
When MASH has progressed to cirrhosis and symptoms of liver failure develop (fluid accumulation, confusion, bleeding), treatment focuses on complications:
- **Diuretics and salt restriction**: prevent fluid accumulation
- **Antibiotics/Lactulose**: prevent bacterial infection and hepatic encephalopathy
- **Variceal bleeding**: medications or endoscopic procedures
- **Liver fibrosis modulation**: medications such as OCA can still contribute to stabilization
Bariatric surgery
ResearchediPositive results in clinical studies, not yet standard treatment
In patients with severe obesity and MASH, weight loss through gastric surgery may be considered. Studies show that these procedures improve hepatic steatosis and in some cases fibrosis markers.
- **Indication**: Usually BMI >35 with comorbidities or BMI >40.
- **Effect**: Weight loss of 50–80% of excess weight; liver histology may improve, but accompanying liver cirrhosis requires caution.
Statins and other cardiovascular medications
ProveniIncluded in official guidelines, or approved by EMA or FDA
MASH patients have increased cardiovascular risk. Statins (cholesterol-lowering drugs) and blood pressure medications are recommended not only for cardiac protection, but also because some data suggest that statins may somewhat reduce liver inflammation.
- **How it works**: Primary effect is lowering cholesterol and inflammatory genes; secondary effect on liver.
Antiviral treatment for MASH + hepatitis
If MASH coexists with hepatitis C or B, antiviral therapy takes priority. Modern antiviral agents for hepatitis C can completely eliminate hepatitis and drastically reduce liver inflammation.
Screening and monitoring tools
ProveniIncluded in official guidelines, or approved by EMA or FDA
Regular monitoring of liver fibrosis is done non-invasively via:
- **Elastography** (transient elastography, SWE): Measures liver stiffness; non-invasive, but accuracy decreases with severe steatosis.
- **Serum biomarkers**: FIB-4, APRI, ELF score and other composite markers from blood tests can estimate fibrosis grade.
- **Ultrasound and MRI**: Imaging to monitor steatosis (fat accumulation) and structural changes.
These tools help determine whether medication is working and whether intensification is needed.
Experimental combination approaches
ExperimentaliOngoing in study setting, outcome still unknown
Research into simultaneous inhibition of multiple pathways is ongoing: FXR agonist + GLP-1, GLP-1 + DGAT2 inhibitor, thyroid hormone receptor agonists + other pathways. This addresses the fact that MASH is multifactorial.
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_This information never replaces a doctor's judgment. Always discuss your situation with your own healthcare provider._