Researchers tested a combination drug called Sacubitril/Valsartan on rats with a serious liver condition where fat builds up and causes damage. The drug worked better than a similar medicine at reducing inflammation, scarring, and early signs of liver cancer. Scientists discovered the drug works by turning off harmful proteins that make liver cells become overactive and create scar tissue. While these results are exciting, the research was done in rats, so doctors will need to test it in humans before recommending it as a treatment.

The Quick Take

  • What they studied: Whether a heart and blood pressure medication combination could help treat a serious liver disease where fat accumulates and causes scarring and inflammation
  • Who participated: Laboratory rats that were specially bred to develop fatty liver disease similar to what happens in humans, plus liver cells grown in dishes
  • Key finding: The combination drug (Sacubitril/Valsartan) reduced liver scarring and inflammation significantly better than one of its components alone, and it also reduced early warning signs of liver cancer
  • What it means for you: This research suggests a new potential treatment for fatty liver disease, but it’s still in early testing stages. People with fatty liver disease should continue following their doctor’s current treatment plans while researchers work toward human trials

The Research Details

Scientists created rats with a genetic change that made them develop fatty liver disease similar to humans. They then fed these rats a high-fat diet and gave them a chemical to speed up liver damage. Half the rats received one medication (Valsartan), while the other half received the combination drug (Sacubitril/Valsartan) for 17 weeks. The researchers examined the rats’ livers under microscopes, tested their blood and tissue samples, and looked at which genes were turned on or off. They also grew liver cells in laboratory dishes and tested how the drugs affected them directly.

Using a rat model that closely mimics human fatty liver disease helps researchers understand how treatments work before testing them in people. Testing the drug on both whole animals and individual cells helps confirm that the benefits are real and shows exactly which biological pathways the drug affects

This study used multiple scientific techniques to verify results, including microscopy, genetic analysis, and protein testing. The researchers tested the drug in both living animals and isolated cells, which strengthens their findings. However, because this is animal research, results may not translate exactly to humans. The study was published in a respected liver disease journal, indicating peer review by experts

What the Results Show

The combination drug Sacubitril/Valsartan reduced liver scarring and inflammation much more effectively than Valsartan alone. When researchers looked at the livers under a microscope, they saw less scar tissue and fewer activated liver cells (the cells that create scars) in the treated rats. The combination drug also reduced early warning signs of liver cancer that typically develop in this disease. These improvements happened over the 17-week treatment period without serious side effects reported. The drug appeared to work by reducing harmful molecules called reactive oxygen species that damage liver cells and trigger inflammation

The research revealed that the drug works by turning off a specific protein called integrin alpha 8, which normally tells liver cells to become overactive and create scar tissue. When researchers artificially increased this protein in liver cells, it made the scarring worse, confirming that reducing it is important for the drug’s benefits. The drug also reduced the activity of an inflammation pathway called the inflammasome, which is like an alarm system in cells that triggers damage when activated

Previous research showed that Valsartan alone has some benefits for liver disease, but this study demonstrates that adding Sacubitril significantly improves results. The combination drug was already known to help heart disease patients, so this research opens a new potential use for an existing medication. The findings align with recent understanding that controlling inflammation and oxidative stress are key to treating fatty liver disease

This research was conducted entirely in rats and laboratory cells, not humans, so results may not translate directly to people. The study didn’t compare the drug to other current fatty liver disease treatments, only to one component of the combination. The exact dose and duration needed for human treatment remains unknown. Additionally, the study used rats with a specific genetic modification, which may not represent all types of fatty liver disease in humans

The Bottom Line

This research suggests Sacubitril/Valsartan may become a useful treatment for fatty liver disease, but it’s too early to recommend it for patients. The evidence is strong enough to justify moving forward with human clinical trials. People currently diagnosed with fatty liver disease should continue following their doctor’s recommendations for diet, exercise, and current medications while waiting for human studies to be completed

People with metabolic dysfunction-associated fatty liver disease (MASH) and their doctors should follow this research closely. Patients with heart disease who already take these medications might be interested in potential additional benefits. Researchers studying liver disease and pharmaceutical companies developing new treatments should pay attention to these findings. People at risk for fatty liver disease due to obesity or metabolic syndrome may want to discuss this emerging research with their healthcare providers

If human trials begin soon, it typically takes 5-10 years for a new treatment to move from early testing to approval. Patients shouldn’t expect this treatment to become available immediately, but the research pathway appears promising

Want to Apply This Research?

  • Users with fatty liver disease could track liver health markers if prescribed by their doctor: monitor liver enzyme levels (ALT, AST) from blood tests every 3 months, track weight and waist circumference weekly, and record diet quality using a simple 1-10 scale daily
  • Users could set reminders to follow liver-protective habits while awaiting new treatments: reduce high-fat food intake, increase physical activity to 150 minutes weekly, limit alcohol consumption, and maintain consistent sleep schedules. The app could provide meal suggestions and exercise tracking specific to liver health
  • Create a liver health dashboard showing trends in weight, exercise frequency, and scheduled lab test dates. Set quarterly reminders for liver function blood tests. Track inflammatory markers through symptom logging (fatigue, abdominal discomfort). Allow users to note when new research updates become available and share results with their healthcare provider through the app

This research was conducted in rats and laboratory cells, not humans. The findings are promising but preliminary. Anyone with fatty liver disease should consult their healthcare provider before making any changes to their treatment plan. This article is for educational purposes only and should not be considered medical advice. Do not start, stop, or change any medications without explicit guidance from your doctor. Human clinical trials are needed before this treatment can be recommended for patient use.