Clinical Research Directory

Efficacy Of Bovine Colostrum In The Treatment Of Severe Alcohol-Associated Hepatitis: A Randomized Controlled Trial

Sponsor: Dayanand Medical College and Hospital

Summary

Severe alcohol-associated hepatitis (sAH)is associated with hepatocellular necrosis, inflammation, hyperactivated immune system, paradoxical immune exhaustion, leaky gut, and alteration in the gut microbiome. The leading cause of mortality is a bacterial infection with multi-organ failure. Pentoxifylline was ineffective and Interleukin-1-based therapies - Anakinra and Canakinumab have not improved survival rates. The granulocyte colony-stimulating factor has shown mixed results. Indian studies improved 90-day survival, while Western studies on Pegfilgrastim have been negative. Corticosteroids decrease the mortality for only a month. In a recent study on Severe alcohol-associated hepatitis, Larsucosterol, a DNA methyltransferase inhibitor, was associated with non-significant improvement in 90-day mortality: 14.7 % (30 mg/day) and 16.67 % (90 mg/day) versus 24.27% on Methylprednisolone. Thus, a more durable treatment of severe alcohol-associated hepatitis is needed. Bovine Colostrum contains many bioactive components such as immunoglobulin G, A, and M (70 - 80 % of total protein), Lactoferrin and Short-chain fatty acids. Bovine Colostrum has 30-100 times higher Lactoferrin concentration than milk. IgG and Lactoferrin synergistically neutralise lipopolysaccharide/ Endotoxin and act on mucosa-associated lymphoid tissue of the leaky gut, transforming it into healthy mucosa. Fewer bacteria and Endotoxins - Pathogen-associated molecular patterns enter the portal circulation to interact with Toll-Like Receptor - 4 of the Liver Kupffer cells. Proinflammatory cytokines such as interleukins-1,6,8 and tumour necrosis factor-alpha, generation decreases, mitigating hepatocyte inflammation, necrosis, and cell death. We therefore conducted a multicenter, phase 3, double-blind, randomized, placebo-controlled trial to determine whether Bovine Colostrum, in addition to standard medical therapy, improves 90-day survival among patients with sAH. Secondary objectives were to assess its effects on liver disease severity, endotoxemia, systemic inflammatory markers, sepsis, and safety.

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