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Extracorporeal cellular therapy unsuccessful in treating alcoholic hepatitis

A recent trial of extracorporeal cellular therapy for severe alcoholic hepatitis did not achieve its primary or secondary endpoints of increased survival compared with standard of care, but did verify that high creatinine and international normalized ratio among those who received the treatment predicted negative outcomes.

“A proteomic analysis of C3A cell products identified numerous proteins with anti-inflammatory properties, such as IL1 receptor antagonist (IL1Ra), the expression of which could be stimulated by various pro-inflammatory cytokines elevated in alcoholic hepatitis,” Julie Thompson, MD, MPH, from the University of Minnesota Medical Center, and colleagues wrote. “Also, C3A cells have been shown to express anti-apoptotic and antioxidative mechanisms that could further dampen the hepatocellular injury caused by inflammation and oxidative stress.”

The researchers enrolled adult patients with a medical history of heavy alcohol abuse who presented with rapid onset of jaundice and coagulopathy in an open-label, randomized study of extracorporeal cellular therapy (ELAD).

Ninety-six patients received ELAD treatment and standard of care while 107 controls received standard of care only. Both groups had comparable time between last alcohol intake, hospitalization, MELD scores (mean, 27.3) and bilirubin (mean, 25.1 mg/dL).

Thirteen of those treated with ELAD did not achieve minimum treatment and 50 patients discontinued treatment.

At 91 days, overall survival did not differ significantly between the two groups, with a mortality rate of 47.9% in the ELAD group and 47.7% in the control group. Mortality rates differed minimally between patients who received 72 hours of treatment and those who received 120 hours of treatment.

Of the 120 patients who had MELD scores less than 28, the researchers observed a trend toward lower mortality rates among patients treated with ELAD compared with the control group (29.4% vs. 43.5%).

Analysis of MELD score’s effect on patients treated with ELAD showed a trend toward poor survival in those with severe kidney damage, defined by creatinine levels higher than 1.5 mg/dL, and severe coagulopathy, defined as INR higher than 2.5. Bilirubin showed no effect on survival in either group.

The ELAD and control groups had similar rates of treatment-emergent adverse events, except for anemia (44% vs. 16%), thrombocytopenia (35% vs. 11%), coagulopathy (31% vs. 12%) and hypotension (31% vs. 17%).

Because of limitations in the current study associated with patient heterogeneity and potential uncertainty of diagnosis in 10% to 20% of the enrolled patients, the researchers initiated a confirmatory study to investigate the reproducibility of these observations in patients with lower MELD and younger age.

“If successful, younger patients with alcoholic hepatitis who do not respond to medical therapy without renal failure or severe coagulopathy could undergo cellular therapy,” the researchers wrote. “This would allow the donor organ pool considered for early transplantation in alcoholic hepatitis to be directed to patients with more advanced coagulopathy or renal failure.” – by Talitha Bennett

Disclosure: Thompson reports she is a consultant for Vital Therapies.