Cirrhosis, MAFLD and the Potential of New Therapies
Researchers at Akero Therapeutics reported early results from a long-term study of efruxifermin, a drug designed to modulate metabolic pathways in the liver. In a 96-week trial focusing on cirrhosis linked to metabolic-associated fatty liver disease, about 39 percent of patients taking 50 mg showed histological signs of improvement, with improvement at 50 mg versus placebo. These findings come from the company’s clinical program and were presented to the medical community.
Therapeutics press release.
What is cirrhosis?
Cirrhosis is a progressive liver disease marked by scarring that replaces healthy liver cells, a process called fibrosis. The scar tissue disrupts the liver’s ability to perform essential functions such as protein synthesis, bile production and metabolism, making it harder to process nutrients and medicines.
Diagnosis is complex and relies on a mix of clinical signs, laboratory tests and imaging. Elastography can stage fibrosis as Metavir F3 or F4, but reversing established cirrhosis depends on multiple factors. The condition typically advances over time and can be associated with metabolic liver disease. Fibrous nodules can raise the risk of cancer development when cells turn malignant.
Causes vary and doctors consider them when choosing treatment. For example, death of hepatocytes can result from alcohol use, hepatitis B and C infections, or metabolic-related liver disease MAFLD. The key development is metabolic related steatohepatitis MASH, a condition that often accompanies overweight, cardiovascular disease and diabetes. Some patients may be considered for newer therapies.
The main aspect of treating metabolic related fatty liver disease is lifestyle modification. Drug therapy may include medicines to improve insulin resistance, omega-3 fatty acids, statins, fibrates and hepatoprotectors.
Efforts to explain the mechanism describe efruxifermin as a drug that mimics the growth factor FGF21, which regulates multiple metabolic pathways. By delivering balanced signals through FGF21 receptors in the liver and adipose tissue, this therapy aims to address the major drivers of disease progression in MAFLD-related cirrhosis.
Advanced therapy can help reduce the extent of cirrhosis, but it should not be viewed as a cure. It can improve fat metabolism and reduce toxins in the liver, supporting hepatocyte health. Histological assessments in trials have shown improvements in fibrosis and liver injury, with some cases moving from late stages toward earlier ones. However, full restoration to a perfectly healthy liver remains unlikely, and outcomes depend on several factors.
Medical professionals emphasize that cirrhosis is not easily reversed in terminal stages. When serious complications such as severe hepatic encephalopathy, significant bleeding, or infections occur, transplantation may be the only viable option.
It is important to note that a drug like efruxifermin focuses on metabolic related steatohepatitis and is not expected to treat alcoholic cirrhosis. In early disease, etiological treatment aims to remove the cause, such as stopping alcohol use, eliminating toxins, treating viral infections with antivirals, or addressing autoimmune causes with appropriate therapy. Treatment for cirrhosis is highly individualized, depending on the dominant clinical syndromes and potential complications.
Physicians also point out that hepatoprotectors have not proven effective at reversing cirrhosis, and dietary and lifestyle strategies play a crucial role. A calorie-balanced diet rich in dietary fiber, vitamins and minerals, with moderate protein and careful salt management, supports liver health alongside medical therapy.