Alcohol is so baked into American culture that it isn’t unnatural to see bottles and cans for sale in grocery stores or gas stations while out around the town. Even those who don’t drink might have a vague understanding as to whether or not they live in a dry county or if they’re allowed to buy alcohol on Sundays. While drinking is a passing enjoyment for most, there’s always a dark side that the average person may not know about.
According to the National Institute on Alcohol Abuse and Alcoholism, between 2015 and 2019, alcohol-associated liver diseases (ALD), alcohol use disorder, and unspecified liver cirrhosis were among the leading causes of alcohol-related deaths due to chronic conditions. This statistic is also backed by the National Center for Drug Abuse Statistics, which states that alcohol abuse, alcoholism, and alcohol use disorder makes up up to 6% of global deaths, killing over 3 million people each year.
Despite these statistics, there are currently no specific therapies or non-invasive biomarkers available for diagnosing or prognosticating ALD. Dr. Tejasav Sehrawat, former postdoctoral fellow in Gastroenterology and Hepatology at Mayo Clinic and future physician and scientist at the Yale School of Medicine, has been dedicated to studying the disease to deepen the current landscape of understanding and to advance the diagnosis and treatment of ALD.
Dr. Sehrawat’s research led to the creation of two research papers, which he published to HEPATOLOGY, a prestigious, peer-reviewed journal published by The American Association for the Study of Liver Diseases. And the work put into these papers laid down the foundation for a U.S. patent titled “Assessing and treating alcohol-associated liver disease”, which Dr. Sehrawat was granted on March 23, 2023.
One of these papers, titled “Circulating extracellular vesicles carrying sphingolipid cargo for the diagnosis and dynamic risk profiling of alcoholic hepatitis”, helped uncover what Dr. Sehrawat hopes to be a more direct but less invasive means of discovery for ALD and a more accessible pathway towards uniform treatments for current and future patients.
A paper from a research team led by Dr. Sehrawat at the Mayo Clinic was presented at the Liver Meeting in Washington D.C. This paper demonstrated the capacity of a novel biomarker to identify infection risk in ALD patients. Infection is the biggest cause of death in these patients. Dr. Sehrawat and his team also published another publication that tests F-652 in a phase 2b clinical trial and proves how this biomarker can help monitor patients dynamically.
The latest discovery from Dr. Sehrawat and his research team was also presented, this time at the Research Society of Alcoholism meeting in Bellevue, Washington. This discovery focused on the disease’s early stages wherein the liver cells, or hepatocytes, go through a condition known as “steatosis” where the cells start to accumulate excessive fat deposits. This collaborative research suggests that steatosis may play a larger role in disease progression than previously believed.
For this project, Dr. Sehrawat and his team generated a novel AI algorithm that could differentiate between alcoholic steatohepatitis (ASH) in ALD versus non-alcoholic steatohepatitis developed from obesity. This project also helped further Dr. Sehrawat’s vast body of biomarker discovery work.
With his collaborators, Dr. Sehrawat also uncovered the importance a gene called HSD17β13 played in fat metabolism and how two regulatory proteins, HNF4α and PPARα, controlled the process. This was done by utilizing new technology called “single cell sequencing” which allows scientists to study cellular DNA and RNA genomics at a new level of granularity that was deemed impossible just a few years ago.
When contacted, Dr. Sehrawat comments, “HSD17β13 polymorphism has previously been associated with reducing the risk of progressing to serious stages of ALD, but no one knew why or how it was functioning in context to the disease until now. The innovative techniques we used in this study have provided a more detailed understanding of ALD’s early stages, offering significant potential for early intervention and disease prevention in the future. By revealing the specific role of HSD17β13 and the counter-balancing act between HNF4α and PPARα, our research paves the way for potential new treatments targeting these molecules, potentially changing the way we tackle ALD in the future.”
Dr. Sehrawat notes that his ongoing work includes discovering the interplay between immune- and liver cells on a single cell level. He’s currently working on detecting the dysfunction between this relation in ALD. He has gone on to say, “This will be the first work published using this novel CITE-sequencing technology in liver diseases. The goal is to detect new immune cell related biomarkers for predicting beforehand those ALD patients that will develop infection on hospital admission.” These works are done in conjunction with Dr. Vijay Shah, the chairman of medicine at Mayo Clinic and Dr. Harmeet Malhi, the chair of research of Gastroenterology at Mayo Clinic.
By continuing his research, Dr. Sehrawat hopes to create a concrete foundation for providing safe, practical alternatives for treatment discovery and implementation. He also hopes to provide a comprehensive atlas of ALD from both inflammation and fatty liver, both of which are crucial aspects of the disease.
ABOUT TEJASAV SEHRAWAT
Dr. Tejasav Sehrawat was a former postdoctoral fellow in Gastroenterology and Hepatology at Mayo Clinic and is a future resident physician-scientist at the Yale School of Medicine. He was previously bestowed the Early Career Investigator in Basic Sciences and Early Career Investigator in Clinical Sciences by the American Association of the Study of Liver Disease.
