Secondary Prophylaxis of Hepatic Encephalopathy With a Probiotic Preparation
Condition: Hepatic Encephalopathy
MeSH terms: Hepatic Encephalopathy; Brain Diseases
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of the proposed project is to study the effects of a probiotic preparation (VSL#3®)
      for the prevention of recurrence of HE (Hepatic encephalopathy) in patients after the
      recovery of an episode of overt HE (secondary prophylaxis)
    

Detailed description: 
      Hepatic encephalopathy (HE) represents a spectrum of neuropsychiatric abnormalities seen in
      patients with liver dysfunction after exclusion of other known brain disease. The Working
      Party at the 11th World Congress of Gastroenterology, Vienna proposed a multi-axial
      definition of HE that defined both, the type of hepatic abnormality (type A, B or C) and the
      duration/characteristics of neurological manifestations (episodic, persistent or minimal HE)
      in chronic liver disease. Overt hepatic encephalopathy occurs in 30%-45% of cirrhotic
      patients and 10%-50% of patients with transjugular intrahepatic portosystemic shunt.
      Development of HE is associated with a poor prognosis. Bustamante et al reported the survival
      probability of 42% at 1 year of follow-up and 23% at 3 years in patients with cirrhosis with
      a first episode of acute HE. The primary treatment of HE is the identification and treatment
      of the precipitating factors. The majority of the drugs used in the treatment of HE are
      primarily directed at the reduction or elimination of the increased neurotoxic ammonia
      levels. A meta-analysis of 22 randomized trials highlighted the lack of data supporting the
      efficacy of nonabsorbable disaccharides; however, the investigators concluded that current
      evidence is insufficient to support or refute the use of nonabsorbable disaccharides for
      treatment of HE. Recent studies with well defined groups however demonstrated the efficacy of
      lactulose. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain
      amino acids, and L-ornithine-L-aspartate also have been shown to have some role. Antibiotics
      are effective in the treatment of HE, but adverse effects and concerns about long-term safety
      have limited their widespread use. Probiotics may have multiple beneficial effects in the
      prevention and/or treatment of HE. All four published studies on the effect of probiotics on
      hepatic encephalopathy have demonstrated efficacy. Treating patients to prevent development
      of a first episode is classified as primary prophylaxis of HE and preventing recurrence of HE
      in patients who had a previous episode of HE as secondary prophylaxis of HE. Sharma et al
      recently demonstrated that lactulose is effective in secondary prevention of HE. This study
      will assess the effects of a probiotic preparation for the prevention of recurrence of HE
      (secondary prophylaxis) in patients after the recovery of an episode of overt HE.
    

Intervention name(s): VSL#3; Placebo
Intervention type(s): Drug; Other
Intervention description(s): VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. Dose would be 1 sachet per day (Each sachet containing 900 Billion CFU). The duration of treatment would be for 24 weeks; Placebo sachets contain corn starch. Dose: 1 sachet per day Duration of treatment: 24 weeks
Other intervention name(s): Probiotic; Dummy Preparation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Hepatic Encephalopathy, probiotics