New treatments offer hope for deadly alcohol-linked hepatitis
Two VCU hepatologists reviewing the state of therapies for alcohol-associated hepatitis point to several new treatments that could cut deaths.
The disease, which is tied to heavy drinking, can strike suddenly. Patients often develop belly pain, jaundice, fever, and confusion. Severe cases can cause organ failure and death within weeks. In the U.S., roughly 10,000–30,000 people are hospitalized each year for severe alcohol-associated hepatitis.
Short-term death rates are high: about 20%–40% die in hospital or within 28 days. Three-month mortality ranges about 30%–50%, and one-year death rates can exceed 50% for people who keep drinking or do not get effective care.
Over the past two decades in the U.S., as deaths from alcohol‑related liver disease have risen, hospital admissions for severe alcohol‑associated hepatitis have increased. The disease affects younger people and more women, and now also drives more liver transplant listings.
For decades, doctors mainly relied on steroids, improved nutrition and abstinence to treat the disease. Steroids help some patients but also raise the risk of infection and do not help everyone. Now researchers are testing medicines that work in new ways, plus approaches that change the gut microbiome.
Multiple promising drugs seek to manage the severe, acute liver injury, especially in patients who do not respond to traditional corticosteroid treatment. They include:
- Larsucosterol, which is a cholesterol metabolite moving toward a phase 3 trial. It has FDA “Breakthrough Therapy” designation and, in phase 2 clinical trials, demonstrated significant reductions in serum bilirubin, a marker of liver function.
- F-652 functions as an IL-22 agonist and is in early clinical trials. It is associated with improved Model of End-stage Liver Disease (MELD) scores, a common marker of liver disease.
- INT-787, which expects to be put into early clinical trials, is a nuclear receptor that plays a major role in regulating bile acid metabolism, lipid metabolism and inflammation.
- Fecal microbiota transplants, are under study, including by the Institute’s Jasmohan Bajaj, M.D., as well as other gut-focused treatments that aim to lower liver inflammation.
Additionally, early liver transplant has improved survival for some patients, with outcomes similar to other causes of liver failure; living donor transplants have shown encouraging results too. Researchers are exploring steroid tapering strategies to cut infection risk without losing benefit.
Experts say these strategies target inflammation, immune signaling, and the gut–liver link, the key drivers of the disease. If the drugs currently in clinical trials pass muster, more patients could survive the acute phase and have better long-term outcomes, especially when transplant and programs to stop drinking are part of care. The review, published in Current Opinion in Gastroenterology, was written by Hanna Blaney, M.D., and Amon Asgharpour, M.D., both of whom are hepatologists with the Institute and VCU Health System.