Q&A: New tool may detect liver fat early on to prevent NASH, NAFLD
There are many people in the United States living with viral hepatitis, which can lead to liver health problems such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
During the COVID-19 pandemic, it is important to increase diagnostics for liver disease because a growing number of studies have found that fatty liver increases the risk for severe COVID-19 symptoms. Healio Gastroenterology spoke with Francois Michelon, CEO of ENDRA Life Sciences, to discuss the relationship between hepatitis and fatty liver disease, ENDRA’s diagnostic tool that may come to market this year that may better detect liver disease and the importance of screening for fatty liver during the COVID-19 pandemic.
Healio: What is ENDRA Life Sciences doing to increase diagnostics?
Michelon: ENDRA's overall goal is to visualize human tissue, similar to an MRI but at 50 times lower cost and, very importantly, at the point of patient care. We have a proprietary technology platform called Thermo-Acoustic Enhanced UltraSound, or TAEUS, that uses radio frequency (RF) energy that is pulsed into the tissue; gets absorbed differentially depending on the water, salt content, and other components of the tissue; and generates sound waves out. It’s very different from a traditional ultrasound, which pulses in sound that bounces off the kidneys, the liver, and the heart, and then sends back an echo. We use RF that is very similar to an MRI in and we generate sound out. Through this technology, we've been able to differentiate tissue types and states, like temperature changes. From that, we've been able to derive interesting clinical applications to address unmet needs. Because we're able to quantify fat in a volume of tissue in a way that ultrasound normally cannot, we believe that there's a high unmet clinical need to detect and monitor non-alcoholic fatty liver disease and NASH at the point of care.
You might be able to characterize different tools based on sensitivity, the ability to correctly identify people with fatty liver above a certain amount, or specificity, the ability to accurately detect people without that condition. The AUROC, or area under the receiver operating curve, summarizes the relationship of sensitivity and specificity across various levels of steatosis. The diagnostic value axis shows that tools like MRI and liver biopsy are very strong in that domain. They have strong sensitivity and specificity, and can detect and measure liver fat quite accurately. But we contend that that's not enough. MRI is bolted to the ground and it's slow. It's not a realistic tool to screen and monitor the estimated 1.4 billion people who have NAFLD and NASH. A liver biopsy is the other tool on that vertical axis of diagnostic value. It’s quite accurate, but it is also an invasive and painful procedure with a risk of death.
We believe that accessibility of those tools is equally important. By accessibility, we mean affordability, safety and ease of use. For instance, ultrasound, blood tests, and medical history combined with BMI check are highly accessible. But none of them are direct measures of fat in your liver, so they fail on the diagnostic value.
Traditional ultrasound and some ultrasound enhancements are getting close to the optimal balance between diagnostic value and accessibility. An ultrasound is relatively cheap, easy, safe and administered at the point of care. But traditional ultrasound is still only qualitative. You can't measure fat accurately in the liver with ultrasound.
At ENDRA, we are trying to position ourselves in the upper right quadrant of the diagnostic-accessibility four-block. You've got an MRI and liver biopsy on the upper left quadrant — high diagnostic value but low accessibility. On the bottom right, you have options like ultrasound, blood tests, medical history — very accessible but no high diagnostic value. We believe there's an opportunity to bring to market something that's both accessible and has high diagnostic value, that's cost effective, safe and better than the common tools used today. We won't be as good as MRI, but we don’t need to be. What we need is something that's considerably more rigorous than a blood test and an ultrasound but a lot less expensive. Our technology will go to market in the second half of this year, for around $50,000 at the point of care.
Healio: Can you speak to the relationship between hepatitis and fatty liver?
Michelon: Hepatitis is one of the root causes of fatty liver, which is a metabolic inefficiency. People are still trying to figure out exactly what the mechanism of action is, but a number of things predispose you to fatty liver, including diabetes, HIV, hepatitis C, lifestyle and obesity. Some interesting other elements include polycystic ovarian syndrome and gut bacteria that produce too much alcohol in your system. Many people may not realize that hepatitis is one of the causes of fatty liver and we see about 325 million people suffering from all types of viral hepatitis, which kills approximately a million people a year. Fatty liver affects over 1 billion people. As fatty liver progresses it irritates the liver, so it becomes inflamed and leads to NASH.
NAFLD and NASH are actually overtaking hepatitis as the leading cause of liver transplants, which shocks me. We believe in an early detection tool for fatty liver that is safe, easy to use and cost effective. Many drug therapies in the pipeline are focused on reducing fat in the liver to stem this disease before it progresses to NASH, fibrosis and then possibly cirrhosis or cancer. We believe there’s a large population suffering from this asymptomatic fatty liver and NASH, and now there are targeted therapies starting to become available. There are going to be treatments, but physicians need to know who to prescribe them to and need a good diagnostic and monitoring tool. Those billion people that have fatty liver are not all obese. They can be marathon runners, with very low body fat or if they have diabetes, they may have a very high level of fatty liver. The hepatitis link is part of this family of liver diseases. They're interrelated. Fatty liver is often asymptomatic and can progress to these other diseases. We are starting to see articles and research coming out about people with fatty liver and NASH being at a higher risk for severe COVID-19 symptoms. There is an obesity and diabetes link with COVID, but there also seems to be an immunoinflammatory link. If you have fatty liver, there may be other immunoinflammatory issues that cause you to suffer more aggressive COVID-19, and viral shedding time is longer for that. So when hepatitis is overtaken by NAFLD and NASH for liver transplants, it’s a major surgery. At ENDRA, we don't think MRI is the right tool to screen NAFLD-NASH sufferers at the early stage, before liver disease requires a liver transplant.
Why is it so important to increase diagnostics?
Michelon: If you can detect NAFLD and NASH early, it can be reversed. It can be reversed if you're disciplined and commit to lifestyle and weight changes. But, because drugs are coming out this year (Zydus’ drug was approved in Asia in March of 2020), if we can detect it early, there's real hope that we could put people on targeted therapies and reverse the disease before it progresses to fibrosis, which is much harder or impossible to reverse. Not everyone knows they have NAFLD-NASH either. So, this is a disease that evolves over time but if we could catch it early with an effective, practical, rigorous, and cost effective tool we think there's a real opportunity to guide clinicians to leverage these new therapies and improve world health.
Healio: Why is it so important during the COVID-19 pandemic to be vigilant for liver health?
Michelon: In addition to the increasing suspicion and linkage of a higher risk for COVID-19 symptoms and longer SARS-CoV-2 viral shedding time associated with fatty liver, many things have been put on hold due to COVID-19, including cancer diagnostics, are going to resurge after operations and hospitals resume. There's going to be more people progressing to stages that are more costly to address, and in some cases clinically, we won't be able to reverse them. So, even during COVID-19, heart disease, cancer, liver health and fatty liver — all of these broadly affecting and very costly long-term health problems —won’t take a pause. Liver disease is a silent epidemic similar to diabetes. There may be an explosion of people with terminal cases who are going to need liver transplants or have fibrosis. We want to address that problem as quickly as possible and that's why we're commercializing our product this year. We have regulatory approval for our product in Europe and we have applied to receive 510(k) from the FDA in the U.S.