None listed
Conditions
Brief summary
Alcoholic hepatitis is an acute deterioration in liver function in the context of excessive alcohol consumption. Those with severe Alcoholic Hepatitis (sAH) have a high short-term mortality. Prednisolone has a modest efficacy in reducing short-term mortality in sAH, but it cannot used in many patients because of contraindications, and if used, it is associated with increased risk of infections. The gut-liver axis modulation through healthy donor faecal microbiota transplantation (FMT) has been proposed as a therapeutic alternative in managing patients with sAH. FMT has been shown to alleviate gut dysbiosis and restore gut microbial diversity. The role of orally delivered FMT capsules in sAH is yet to be explored. We hypothesize that orally delivered FMT capsules is a safe and efficacious therapy in patients with sAH. Aims of this study are: (i) to assess the gut microbial signatures in those with sAH, followed by (ii) A pilot randomised controlled trial to assess the safety and efficacy (primary outcome: 28- day mortality) of FMT compared to prednisolone in patients with sAH.
Interventions
Faecal microbiota transplantation (FMT) using oral FMT capsules.
Those randomised to FMT arm will have 6 capsules/day for the first 6 days (36 capsules in total) amounting to ~25g of stool in total. Most patiets will be in-patients during the treatment period and capsule swallow will be directly observed. Those patients who are discharged prior to day 6 will have a phone consultation by the study co-ordinator every morning to confirm taking the capsules till they complete the 36 capsules.
Sponsors
Northern Adelaide Local Health Network (NALHN)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Individuals meeting the clinical and biochemical criteria for severe alcoholic hepatitis as defined by: 1) Rapid development or worsening jaundice and liver related complications 2) Serum total bilirubin > 80 mmol/L, ALT and AST levels <400 U/L, with the AST/ALT ratio >1.5 3) Documentation of persistent heavy alcohol use until 8 weeks before onset of symptoms 4) Average alcohol consumption of >80g/ day for men and >60g/day for women 5) Maddrey’s Discriminant Function (DF) score greater than or equal to 32 AND MELD score 21-30 Liver biopsy is not required to confirm the diagnosis of severe alcoholic hepatitis.
Exclusion criteria
1) Cessation of alcohol consumption for >2 months prior to randomization 2) Concomitant liver disease including viral hepatitis, autoimmune hepatitis, drug induced liver injury, acute pancreatitis, HIV and active tuberculosis 3) High grade encephalopathy requiring endotracheal intubation for airway support 4) Uncontrolled upper gastrointestinal bleeding 5) Acute kidney injury (AKI) or hepato-renal syndrome (HRS) with serum creatinine >500 mmol/L or requirement for renal replacement therapy 6) Hepatic or extrahepatic malignancy 7) Pregnancy or nursing 8) Uncontrolled infections or sepsis 9) Anaphylactic food allergy 10) Prebiotic, probiotic or antibiotic use within 4 weeks of enrolment 11) Participant unable to provide informed consent
Outcome results
None listed