Gut–Liver Axis Modulation with IgG-Enriched Oral Immunotherapy in Severe Alcohol-Associated Hepatitis

Background: There are currently no FDA-approved treatments for severe alcohol-associated hepatitis. Bovine Colostrum, a natural product rich in immunoglobulins and lactoferrin, has been shown to neutralize endotoxins and repair the leaky intestinal mucosal barrier. We aimed to evaluate the efficacy and safety of bovine Colostrum in treating severe alcohol-associated hepatitis.
Methods: This phase 3, parallel-group, double-blind, randomized (1:1), placebo-controlled trial was conducted across five academic hospitals in India. Patients with probable severe alcohol-associated hepatitis were enrolled. Randomization was performed centrally using the Trans European Network for Clinical Trials Services. Participants received either 20 g of freeze-dried Colostrum or a placebo (pasteurized bovine milk powder) three times daily for 4 weeks. Treatment allocation was masked from patients, investigators, and statisticians. The primary outcome was 90-day survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov ID NCT02473341(Completed).

Findings: Between 2017 and 2023, 174 patients were enrolled: 89 in the colostrum group and 85 in the placebo group. Survival at 90 days was significantly higher in the colostrum group, at 89ꞏ9% (80/89) [MELD score - 30ꞏ2 (27ꞏ9, 33ꞏ4)], compared to 57ꞏ6% (49/85) in the placebo group [MELD - 31ꞏ5 (27ꞏ9, 34ꞏ2)] (p<0ꞏ0001), with a hazard ratio of 0ꞏ18 (95% CI: 0ꞏ09-0ꞏ38, p<0ꞏ001). Secondary outcomes: survival at 30 days was significantly higher (p<0ꞏ0001), with notable reductions in serum endotoxin levels [1ꞏ4 (0ꞏ9, 1ꞏ7)] vs. [-0ꞏ2 (-0ꞏ5, 1ꞏ0)] (p<0ꞏ001), TNF-α levels [6ꞏ0 (3ꞏ0, 11ꞏ0) vs. -6ꞏ0 (-10ꞏ0, 9ꞏ0)] (p=0ꞏ01), and fewer sepsis episodes at one month in the colostrum group (60) compared to the Placebo (75) (p=0ꞏ01). Serious adverse events were mild, occurring at similar rates in both groups.

Interpretation: Bovine Colostrum significantly improved 90-day survival among patients with very severe alcohol-associated hepatitis, possibly by restoring gut barrier function, reducing endotoxemia, hepatic inflammation, and Sepsis.