Active — Not RecruitingPhase 3

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

India174 participantsStarted 2017-11-14

Plain-language 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

Who can participate

Age range18 Years – 75 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Onset of jaundice within prior 8 weeks * Ongoing consumption of \> 40 (female) or 60 (males) g alcohol/day for 6 months or more, with less than 60 days of abstinence before the onset of jaundice * Aspartate aminotransferase \> 50, aspartate aminotransferase/alanine aminotransferase \> 1.5, and both values \< 400 IU/L * Serum bilirubin (total) \> 3.0 mg/dL * Liver biopsy confirmation in patients with confounding factors including possible ischemic hepatitis (eg, severe upper gastrointestinal bleed, hypotension, or cocaine use within 7 days); possible DILI; uncertain alcohol use assessment (eg, patient denies excessive alcohol use); and atypical laboratory tests (eg, AST \< 50 IU/mL or \> 400 IU/mL, AST/ALT ratio \< 1.5), antinuclear antibody \> 1:160 or SMA \> 1:80 * Maddrey's discriminant function ≥ 32 assuming a control prothrombin time of 12 seconds * Model for End-stage Liver Disease score \> 20 Exclusion Criteria * Uncontrolled infections * Multiorgan failure * Uncontrolled upper gastrointestinal bleeding. "However, patients with recent Upper Gastro Intestinal bleeding, without significant hypotension that is controlled for \>48 hours, will be included in the study." * Preexisting kidney injury with serum creatinine \> 2.5 mg/dL * Other underlying liver diseases including hepatitis B infection,\* autoimmune liver diseases, Wilson disease, suspected drug-induced liver injury\* * Hepatocellular carcinoma or other active malignancies except skin canc…

What they're measuring

Survival

Timeframe: 3 month

Trial details

NCT IDNCT02473341

SponsorDayanand Medical College and Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-08-01