Fatty Liver Disease: Understanding NAFLD vs AFLD Causes, Symptoms, and Prevention

Fatty liver disease (FLD) can lead to severe liver damage, including cirrhosis and liver cancer. Doctors classify FLD into two main types: Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Fatty Liver Disease (AFLD). AFLD is caused by excessive alcohol consumption and can be reversed by stopping alcohol intake. NAFLD is linked to obesity, insulin resistance, and metabolic syndrome and can progress to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to liver cancer. Lifestyle management, including dietary changes and regular monitoring, is critical for preventing and controlling both types of fatty liver.

The U.S. Food and Drug Administration (FDA) is exploring the use of a non-invasive liver measurement as a surrogate endpoint for certain metabolic dysfunction-associated steatohepatitis (MASH) patients. This move, if implemented, could significantly accelerate drug development in the MASH space, which is a severe form of fatty liver disease that can lead to severe scarring and impaired liver function [1].

Currently, MASH is primarily evaluated through multiple liver biopsies, which can miss diffuse signs of the condition due to its uneven distribution across the organ. The FDA has accepted a letter of intent to qualify liver stiffness, as measured by transient elastography, as a reasonably likely surrogate endpoint in MASH patients with moderate to advanced fibrosis. This submission was made by Céline Fournier, Ph.D., vice president of medical affairs at Echosens, a manufacturer of FDA-cleared, ultrasound-powered liver scanners, and includes letters of support from Eli Lilly, Boehringer Ingelheim, and Novo Nordisk [1].

The liver stiffness biomarker can predict the risk of death or liver-related events in MASH patients, according to the letter. The proposed non-invasive method could provide a safer and more accessible way to track disease progression and responses to treatment. This could also improve trial recruitment and help overcome challenges tied to running adequately powered studies [1].

"This proposal represents an important step toward adopting non-invasive tests in drug development for MASH," said Frank Anania, M.D., director of hepatology and nutrition for the FDA’s Center for Drug Evaluation and Research, in an August 27 release [1]. The news has positively impacted the stocks of several MASH therapy developers, including Madrigal Pharmaceuticals, Viking Therapeutics, Inventiva, and Altimmune [1].

While the timing and potential implementation of this change remain unclear, the FDA's move away from biopsies toward non-invasive measures of efficacy is seen as a significant positive for clinical development in the MASH space [1].

References:
[1] https://www.fiercebiotech.com/biotech/fda-considers-non-invasive-liver-endpoint-trials-sending-mash-biotechs-stock