NASH Treatment Advances: New Fatty Liver Disease Medications on the Horizon

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• NASH Complexity and Treatment Challenges
• Disease Heterogeneity Explained
• Current Treatment Limitations
• Combination Therapy Approach
• Future NASH Treatment Outlook
• Full Transcript

NASH Complexity and Treatment Challenges

Dr. Scott Friedman, MD, describes non-alcoholic steatohepatitis as one of the biggest challenges in his career. He explains that NASH is far more complex than initially understood. The disease involves multiple features including liver fat accumulation, inflammation, cellular injury, and liver scarring.

Dr. Scott Friedman, MD, emphasizes that this complexity explains why no medications have received FDA approval for NASH treatment despite extensive research. The metabolic programming that causes the body to retain fat is deeply hard-wired, making therapeutic intervention particularly challenging.

Disease Heterogeneity Explained

Dr. Scott Friedman, MD, reveals a critical insight about NASH heterogeneity. Patients who appear to have identical disease under microscopy may actually have different underlying drivers. Some patients develop NASH primarily due to toxic fat accumulation, while others have overactivated stellate cells or specific inflammatory cell types.

This variability means different patients may require different treatment approaches. Dr. Scott Friedman, MD, notes that even the most promising NASH medications typically benefit only 30-50% of patients. This suggests multiple disease pathways exist within the NASH diagnosis category.

Current Treatment Limitations

The interview with Dr. Anton Titov, MD explores why current NASH treatment approaches fall short. Dr. Scott Friedman, MD, explains that blocking one pathway might drive compensation through other mechanisms. This multi-pathway nature of NASH creates significant treatment challenges.

Dr. Friedman acknowledges the frustration within the medical community about lacking approved NASH medications. He compares NASH treatment development to hepatitis C therapy, noting that viral targets are simpler than systemic metabolic diseases. The search for NASH's "Achilles heel" continues without clear single-target solutions.

Combination Therapy Approach

Dr. Scott Friedman, MD, advocates for combination therapies as the future of NASH treatment. Multiple drugs with complementary mechanisms of action may be necessary to address the disease's complexity. This approach could target fat reduction, inflammation control, and fibrosis prevention simultaneously.

Dr. Friedman suggests that personalized medicine may become essential for NASH management. Treatment selection might depend on individual patients' dominant disease drivers. Combination regimens could involve two or more medications to achieve maximal therapeutic effect.

Future NASH Treatment Outlook

Dr. Scott Friedman, MD, provides optimistic predictions about NASH medication approvals. He anticipates the first FDA-approved NASH drugs will emerge within the next couple of years. However, he cautions that progress will be iterative and gradually progressive.

Dr. Scott Friedman, MD, emphasizes the need for both aggressive drug testing and patience. Basic science discoveries must continue to identify new NASH treatment targets. The therapeutic landscape for fatty liver disease will evolve slowly but steadily toward more effective options.

Full Transcript

Dr. Anton Titov, MD: Why are there no medications approved yet for non-alcoholic steatohepatitis? It is so despite all the research.

Dr. Scott Friedman, MD: You are a renowned researcher in fatty liver disease and its genetics and metabolic effects. This is one of the biggest challenges certainly that I've confronted in my career. It reflects the fact that NASH is a much more complex disease than we first gave it credit for.

We know that there are a number of features that occur in NASH. I mentioned most of them already: the liver fat, the inflammation, the injury, the scarring of the liver.

Dr. Anton Titov, MD: What we don't know is whether every patient who has NASH that we diagnose under the microscope has exactly the same disease.

Dr. Scott Friedman, MD: It could be that some patients have NASH primarily because they have too much fat and the fat is toxic. Others because their stellate cells may be more activated, and others yet because they have too much of certain kinds of inflammatory cells.

So we're just starting to think about the fact that not all NASH is identical. Even if it looks the same under the microscope, it could be that the pathways that lead to the development of NASH may be different across different patients.

And that could explain why no drug has had a benefit in all patients. Even the drugs that look most promising typically only benefit about a third, at most half of the patients.

That may suggest that not everybody has the same disease drivers in their livers to cause the NASH picture, even if it looks the same under the microscope. It may also be that NASH is a multi-pathway disease.

And if you block one pathway, other pathways are driven to create more fat and inflammation. And so we may need multiple targets and multiple drugs with different mechanisms of action that are complementary.

That's sort of where the field is starting to go now. We think more about combination therapies for NASH because we want to hit more than one target.

And we don't really have a clear understanding of what is the Achilles heel from a treatment perspective. Is there one pathway in NASH, or is there one molecule that drives the disease in every patient with NASH?

So far, we haven't described that so-called Achilles heel. And so again, we're still left trying to use different combinations of treatments for NASH.

The programming of the body and the liver to hold on to fat is very hard-wired. And it's going to take a deeper understanding and a bit more patients before we come up with something that really will improve therapy of NASH.

I don't think we're far away in terms of our first approved drugs for NASH. I think we'll see that within the next couple of years.

But it will be an iterative, slowly progressive process where we may have to individualize therapies or combinations. And we may have to use even more than one or two drugs, as I mentioned, to get a maximal effect.

So yes, it's been very frustrating that we don't have an approved drug yet for NASH. In the greater scheme of things, I think the time horizon has been relatively short.

If you look at a disease that turned out to be easier to treat, that would be hepatitis C, even though we had the viral sequence as early as 1989. It was really only in 2010 that we finally developed really effective, well-tolerated curative therapies.

And frankly, hitting a virus is a lot easier than hitting a systemic disease like metabolic syndrome associated with NASH. And so, I think we need to be both assertive and aggressive in testing new drugs for NASH.

We must unearth more basic science discoveries that define targets in NASH. But we also need to be more patient in anticipating slow but steady progress in the therapeutic landscape of NASH.