Research News

Cleveland Clinic researchers have discovered that a molecule called HSPB1 contributes to alcohol-associated hepatitis, one of the most dangerous consequences of alcohol use disorder. The new study published in Hepatology Communications suggests that HSPB1 levels in the blood could be more helpful as a biomarker than alcohol consumption to prioritize individuals in need of liver transplant for alcohol-associated hepatitis. 

“We know that stopping drinking is the most important intervention, but it’s also the hardest,” says Jeannette Messer, DVM, PhD, senior author of the study. “That means we need better tools to predict how the disease will progress.” 

Liver transplant for alcohol-associated hepatitis is the most effective treatment, but the procedure is complex and requires long-term care to ensure success. With no way of predicting who needs a new liver, using this technique preventatively is unrealistic. Organ transplants are major procedures that should only be used when they’re needed. Prioritizing individuals on the transplant list is a constant challenge many researchers (including some from Cleveland Clinic) are working to address.  

To find potential predictive tools, Dr. Messer and her team analyzed blood and tissue samples from the Northern Ohio Alcohol Center, a world-class research center which provides resources to support the efforts of clinicians and basic scientists at Cleveland Clinic, Case Western Reserve University, and other institutions across northern Ohio. The Alcohol Center combines research on how alcohol affects our organs, especially our livers, with clinical expertise to improve outcomes of alcohol-related diseases. 

What is HSPB1 and how is it related to hepatitis? 

HSPB1 (Heat Shock Protein Family B [Small] Member 1) is a protein that helps cells survive and repair themselves during extreme conditions.  Part of HSPB1’s function is to signal pro-inflammatory molecules to clear debris. The more HSPB1 there is, the more inflammation there will be. One of the main molecules HSPB1 triggers, TNF alpha, causes inflammation in alcohol-associated hepatitis at high levels.   

Dr. Messer's team found that blood and tissue levels of HSPB1 were measurably higher in individuals with alcohol-associated hepatitis. High levels of the molecule also correlated with TNF alpha levels, and with disease severity. These findings were consistent in humans and preclinical models, which according to Dr. Messer means a simple blood test measuring HSPB1 could predict who is at risk for alcohol-associated hepatitis.  

“While more research is needed, it’s tempting to imagine a future where doctors can use a simple blood test to determine who might benefit from preventative liver transplants for alcohol-associated hepatitis,” Dr. Messer says. “Getting them on the transplant list early could help improve their outcomes.” 

Dr. Messer’s team also found that blocking HSPB1 in alcohol-treated liver cells led to reduced levels of TNF alpha. These results suggest that the molecule is a direct cause of the inflammation that marks hepatitis and not just correlated with it.  

This distinction is critical when it comes to developing potential therapeutics. Immunosuppression (which could stop inflammatory response causing damage) is not a good option for patients with alcohol-associated hepatitis because they’re already at high risk of infection, Messer says. Their team’s preclinical results show a more targeted treatment approach is worth investigating. 

“We’re really interested in how protective responses go wrong,” she says. “If we can figure out how to keep HSPB1 in the zone where it promotes healing instead of harm, we might be able to change the trajectory of this disease.”