META ANALYSIS

GROUP PROPOSAL

Presenters:
Nuñeza, Klaudine
Servando, Allisone Eunice
Soriaso, James Nicole

la
TITLE:
The Efficacy of Probiotics as Secondary Prophylaxis in
Minimal Hepatic Encephalopathy in Comparison to
Lactulose:
A Meta-Analysis Approach
 CHAPTER 1
Introduction
• Hepatic Encephalopathy is one of the complications of
long term, decompensated liver cirrhosis and broadly
defined as having altered mental condition and abnormal
cognitive functions in the presence of liver failure.
• It is usually qualified using the West Haven Grading
System and is classified as covert versus overt Hepatic
Encephalopathy.
• It is then further graded from Grade 1 to 4 as Minimal,
Mild, Moderate, and Severe respectively.
• Probiotics, is defined by Food and Agriculture
Organization of the United Nations (FAO) and the WHO
as “live microorganisms which when administered in
adequate amounts confer a health benefit on the host”
• Probiotics can stimulate gut microbiota modulation which
plays an important role in enhancing intestinal mucosal
barrier function.
• This contributes to a decrease in the levels of ammonia in
the blood consequently preventing hepatic
encephalopathy to occur.
• Lactulose has laxative characteristics causing a decrease
in the synthesis and uptake of ammonia by decreasing
colon pH and also reducing glutamine uptake.
• Lactulose is converted into monosaccharide by normal
flora and used as a food source so that the growth of
normal intestinal flora will suppress other bacteria that
produce urease.
 CHAPTER II
Rationale of the Study

• There is a limited intervention and standard treatment in

the management of hepatic encephalopathy in the
Philippines.

• This study aims to seek other modalities such as utilizing

probiotics in patients with minimal hepatic encephalopathy
by compiling evidences of foreign studies.
Research Question

• In patients with minimal hepatic encephalopathy, is there

a significant reduction in the occurrence rate of overt
hepatic encephalopathy compared to standard therapy ?

• Is there a significant decline in the hospital admissions of

patients with minimal hepatic encephalopathy using
probiotics compared to lactulose ?
Objectives of the Study:

• This study aims to review the results of multiple

randomized control trial (RTC) studies in using Probiotics
as secondary prophylaxis on Minimal Hepatic
Encephalopathy.

• To determine the significance of Probiotics in preventing

the occurrence of overt Hepatic Encephalopathy in patient
with minimal hepatic encephalopathy
 CHAPTER III
METHODOLOGY

ELIGIBILITY CRITERIA

INCLUSION CRITERIA
EXCLUSION CRITERIA
 INCLUSION CRITERIA
• POPULATION ATTRIBUTES
– Out patients with minimal hepatic encephaloptahy regardless of
the etiology
– Patients age 18 to 75 years old
– Male and female sexes
– All races
– Patients with stable comorbidities
 EXCLUSION CRITERIA
• Patients with overt hepatic encephalopathy
• Patients with history of taking lactulose or any antibiotics, and alcohol intake in
the past 6 weeks
• Patients receiving secondary prophylaxis for spontaneous bacterial peritonitis
• Patients with previous transjugular intrahepatic portosystemic shunt or shunt
surgery
• Patients with significant comorbid illness such as heart, respiratory or renal
failure and any neurological disease
• Patients with hepatocellular cacinoma
• Patients receiving psychoactive drugs
• Non-RCT studies
• Date of Interest: 2008-2022
• Exposure of Interest: Patients with minimal hepatic
encephalopathy
• Age of Interest: 18 years old to 75 years old
• Gender of Interest: Male and Female
• Language: English
• Participants: Cochrane Library, PubMed, Elsevier,
Clinical Trials.gov.MedRvix, Herdin Plus
• Setting of Interest: Out Patients
• Study Design: Randomized Clinical Trials
• Prefilled Eligibility Criteria
• Types of Participants:
• Patients with Minimal hepatic encephalopathy
• Adult patients (Ages 18 to 75 years old)
• Male or Female
• All races
• Outpatient setting
III.
• Types of Intervention
– Probiotics 3 capsules a day
– Lactulose 30-60ml/day

• Characteristics that may alter result of intervention:

– Availability of product
– Adverse drug reaction
– Intolerance to medication
– Compliance to medication
– Economic burden
IV. Selecting, Prioritizing and Grouping Review Outcomes

– Efficacy as a secodary prophylaxis in patients with minimal

hepatic encephalopathy based on:
• Improvement in the Psychometric assessment
• Reduction of levels of ammonia in blood
• Improvement of Child–Turcotte–Pugh (CTP)
• Study Design
– Randomized Control Trials

• Eligibility based on publication status

– Published studies, peer reviews and grey literature pertaining to
inclusion and exclusion criteria.
 Chapter IV
Searching and Selecting Studies

Databases Selected:
– Cochrane Library
– PubMed/ncbi
– Clinical Trials.gov.
– Herdin Plus
• Designing Search Strategies
– PICO FORMAT
• P: Patients with minimal hepatic encephalopathy regardless of etiology
• I: Probiotics
• C: versus Lactuose
• O: Reducing the occurence of overt hepatoencephalopathy
• Search Strategy:
– Terms to search for health condition (Minimal hepatic encephalopathy,
Portosystemic encephalopathy, Liver cirrhosis)
– Terms to search for the type of study design to be included (Randomized Control
Trial)
– Terms to search for intervention (Probiotics, Gut microbiota modulators)
• Timing of Searches:
– Within 15 years ( 2008-2022)
Search Filters:
Documenting and Reporting the search Process:
• Guidance from medical or healthcare librarian
• Bibliographic database are copied and pasted in an appendix

Identifying Multiple Reports

• Title of Study
• Identification number
• Name of authors
• Date and Duration of the study
• Date published
Typical Process for Selecting Studies
• Merging results from different sources
• Examining study title and abstract and removing obviously irrelevant
results
• Retrieving and reviewing potentially relevant reports
• Comparing results from different studies
Selecting excluded studies
• Patients with overt hepatoencephaolopathy
• Patients with comorbidities or in immunocompromised state
• Patients who have taken lactulose, alcohol,any antibiotics,
psychoactive drugs within 6 weeks
• Non-RCT studies
 Retrieval Studies
PUBMED COCHRANE CLINICALTRIALS.GOV HERDIN PLUS
64 2 10 0
Identification

76 non duplicate
Criteria Applied

Inclusion/Exclusion 59 Articles excluded

Criteria applied after title and abstract screen
Screening

17 Articles Retrieved
Eligibility

Inclusion/Exclusion 9 Articles excluded 4 Articles excluded

Criteria applied after full text screen During data extraction
Inclusion

4 Articles Included
 Research Timeline
Activity Weeks 1 2 3 4 5 6 7 8 9
Phase

Reading and
Research

Topic Presentation

Topic Interpretation

Analysis Results
 Reference
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PMID: 26087788; PMCID: PMC4694740.

• Wong SN, Ong JP, Labio ME, Cabahug OT, Daez ML, Valdellon EV, Sollano JD Jr, Arguillas
MO. Hepatitis B infection among adults in the philippines: A national seroprevalence study.
World J Hepatol. 2013 Apr 27;5(4):214-9. doi: 10.4254/wjh.v5.i4.214. PMID: 23671726;
PMCID: PMC3648653.

• Dalal R, McGee RG, Riordan SM, Webster AC. Probiotics for people with hepatic
encephalopathy. Cochrane Database Syst Rev. 2017 Feb 23;2(2):CD008716. doi:
10.1002/14651858.CD008716.pub3. PMID: 28230908; PMCID: PMC6464663.