Professor Gregory Steinberg, of McMaster University and Co-Director of the Centre for Metabolism, Obesity and Diabetes, shares insights on the growing impact of metabolic liver disease and the breakthroughs shaping its future. From understanding MASH to therapies that may reverse liver damage, his work is redefining metabolic health.
What inspired you to focus your research on metabolic diseases and liver health?
At the McMaster University Centre for Metabolism, Obesity and Diabetes Research, my laboratory has focused on how the body regulates energy, particularly how we process and store fats and sugars. Over time, it became clear that the liver sits at the centre of this system. It plays a key role in controlling blood sugar, regulating lipid levels, and maintaining overall metabolic balance.
What really drew me to this area is that when these processes become disrupted, you don’t just see one disease, you see a cluster of conditions that tend to occur together, including fatty liver disease, type 2 diabetes, and cardiovascular disease. In many ways, the liver is at the centre of metabolic health, and when it goes wrong, multiple diseases follow.
The opportunity to better understand what is happening in the liver, and to develop new ways to target those pathways, offers a chance to impact multiple diseases at once. That has been a major motivation for my work.
For readers who may not be familiar, how serious is metabolic dysfunction-associated steatohepatitis (MASH), and why has it been so difficult to treat effectively?
MASH is a more advanced and serious form of fatty liver disease. It begins with fat accumulating in the liver, but in some individuals this progresses to inflammation and scarring, known as fibrosis. Over time, this scarring can become severe and lead to cirrhosis, liver failure, or liver cancer.
One of the main challenges in treating MASH is that it is not caused by a single problem. It is driven by a combination of issues, including the body not responding properly to insulin, difficulty processing and storing fats, and chronic low-level inflammation. Because of this, targeting just one pathway often is not enough to stop the disease from progressing.
Another important aspect is that MASH is closely linked to broader metabolic health. Many patients also have type 2 diabetes and are at increased risk of cardiovascular disease. You can’t treat MASH in isolation, you have to address the underlying metabolic dysfunction that contributes to it.
Your team’s findings suggest this drug could reverse liver fibrosis—why is that such a significant breakthrough compared to current treatment approaches?
In collaboration with Espervita Therapeutics, we are developing a compound called EVT0185 that targets how the liver handles fat, including both fat production and fat breakdown. These are core processes that drive the development of fatty liver disease and its progression.
What is particularly encouraging from our preclinical studies is that we are seeing not only reductions in liver fat, but also meaningful reversal of fibrosis and liver cancer. Reversing fibrosis has been a major goal in the field, because fibrosis is the key step that leads to more advanced disease, including cirrhosis and liver failure. Very few therapies have been able to reverse established scarring, which has been a major limitation.
In addition, EVT0185 improves blood sugar and lipid levels, which are important drivers of type 2 diabetes and cardiovascular disease. This reinforces the close connection between liver health and overall metabolic health. If we can reverse fibrosis and improve metabolic health at the same time, we have the potential to change the course of the disease.
