Gut-Liver Axis Modulation With IgG-Enriched Immunotherapy in Severe Alcohol-Associated Hepatitis

Summary

Severe alcohol-associated hepatitis 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. In this study, we aimed to assess the effectiveness and safety of Gut-Liver Axis Modulation with IgG-Enriched Oral Immunotherapy(Bovine Colostrum) in Severe Alcohol-Associated Hepatitis

Conditions

• Alcoholic Hepatitis

Interventions

DRUG

Bovine Colostrum

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Pasteurized Bovine colostrum as a freeze dried powder (20 gm thrice a day) for 4 weeks. \+ Antibiotics + Diuretics +Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed +drugs for HE if indicated

DRUG

Placebo

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Placebo (Pasteurised Milk Powder) 20 gms thrice a day for 4 weeks \+ Antibiotics + Diuretics + drugs for HE + Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed + if indicated.

Sponsors & Collaborators

• Dayanand Medical College and Hospital

  lead OTHER

Principal Investigators

• Sandeep Singh Sidhu, DM · Dayanand Medical College and Hospital, Ludhiana, Punjab, India

• Ajay Duseja, DM · PGI Hospital, Chandigarh, India

• Shalimar S, DM · All India Institute of Medical Sciences

• Dharmesh Kapoor · Gleneagles Global Hospital, Hyderabad

• Sandeep Nijhawan · SMS Hospital, Jaipur, India

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-11-14

Primary Completion

2024-08-01

Completion

2025-09-01

Countries

• India

Study Locations