New Study Explains Differences in Liver Disease Treatment Outcomes
How Treatments Steer the Immune System in Different Directions
BOSTON — One of the deadliest emergencies in liver medicine, severe alcohol‑associated hepatitis (AH) is a fast‑moving form of liver failure triggered by intense inflammation. Up to half of patients die within a month; as many as 60 percent die within six months.
Yet clinicians have struggled to understand why patients with the same clinical profile at admission can veer onto completely different trajectories once treatment begins. A Beth Israel Deaconess Medical Center‑led study published in Hepatology helps explain why: the treatments themselves can alter the body’s immune response, and those early shifts influence how patients ultimately fare.
“What we see in these patients is not a static disease but a moving target,” said senior author Gyongyi Szabo, MD, PhD, Chief Academic Officer for Beth Israel Lahey Health and BIDMC. “The immune system shifts over days and weeks, and importantly, it shifts because of the treatment we give. Even when people feel better, many immune signals are still off months later, which tells us the system remains vulnerable and why some patients relapse or get into trouble again.”
In a multicenter collaboration among BIDMC, UT Southwestern Medical Center, UMass Chan Medical School, Cleveland Clinic, and the University of Louisville School of Medicine, Szabo and colleagues followed nearly 90 patients for six months, measuring dozens of immune and inflammatory molecules at multiple time points. As they analyzed the data, a clearer picture of AH emerged: treatment itself helps shape the course of the disease, steering the immune system in different directions over time.
Szabo and colleagues compared patients treated with prednisone — the long‑standing first‑line therapy that broadly dampens inflammation—to those receiving anakinra, a newer investigational approach that blocks a specific inflammatory signal implicated in AH. Distinct patterns emerged.
Treatment with anakinra initially quieted one pathway but appeared to cause others to flare. Several inflammatory molecules spiked around day seven before decreasing later, perhaps explaining why some patients worsen early while others begin to recover. By contrast, patients on steroids showed broad suppression of inflammatory signals paired with a rise in molecules associated with tissue repair. Neither response is universally helpful.
To make sense of these diverging paths, the team examined the dozens of immune signals — or biomarkers — they had been tracking in patients’ blood. They found that the markers predictive of poor outcomes in one treatment group didn’t signal poor outcomes in the other. Each therapy appeared to shape the immune response in its own way, and the clues to how patients would fare depended on which therapy they received.
The findings suggest that treatment for severe AH may need the same level of personalization clinicians already apply to cancers or autoimmune diseases. Instead of relying on one standard therapy for everyone, doctors may one day match patients to drugs based on their individual immune profiles.
“This work tells us we need to meet the disease where it is,” Szabo said. “If we can listen to what the immune system is doing — not just at day zero, but as it shifts — we can make smarter choices for our sickest patients.”
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a leading academic medical center, where extraordinary care is supported by high-quality education and research. BIDMC is a teaching affiliate of Harvard Medical School, and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox.
Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.
