Meta-analysis of probiotics efficacy in the treatment of minimum hepatic encephalopathy.

N/A

• To help support cognitive function and reduce levels of ammonia in the blood practitioners should consider recommending probiotics in patients with MHE.

Introduction

• Minimum hepatic encephalopathy (MHE) is frequently missed as it is hard to diagnose, yet it occurs in 20-80% of cirrhosis patients.

• Without treatment the risk of cognitive decline as well as mortality rate increases by 50%.

• The study aimed to evaluate current evidence on the outcome of treating MHE with probiotics.

Methods

• A systematic search of PubMed, China National Knowledge Infrastructure and Wanfang was conducted for RCT’s up to March 2023.

• Of 361 studies, 18 RCTs (n=1226, ages 40-60) were included. Study duration ranged from one to three months.

• Search terms included “probiotics”, “Lactococcus lactis”, “Bacillus subtilis”, “Lactobacilli”, “Lactobacillus”,”Saccharomyces”, “Bifidobacterium”, “minimal hepatic encephalopathy”, “overt hepatic encephalopathy (OHE)” and related terms.

• All research were RCT’s investigating mild or subclinical HE where probiotics compared to a placebo or blank control.

• Exclusion criteria were non populations studies, conference articles, case reports, reviews and non-RCT’s or insufficient data.

• Outcome measures: blood ammonia level, alanine aminotransferase level (ALT)) and Model for End-Stage Liver Disease (MELD) score, MHE remission rate, MHE incidence and a psychometric test, specifically number connection test A (NCT A) and digit symbol test (DST).

• Depending on heterogeneity a fixed- or random-effects model was applied.

 Results

• Random effects-model:

  Blood ammonia (14 RCTs) was lower with probiotics (SMD = -2.68, 95% CI: - 3.90 to -1.46, p<0.0001).

  ALT (8 RCTs) was lower with probiotics (MD=-11.10, 95% CI:-16.17 to -6.03, p<0.0001).

  NCT reaction time (9 RCTs) was significantly lower with probiotics (MD=-12.54, 95% CI: -21.63 to – 3.46, p=0.007).

  DST score showed now significant difference (SMD- 0.81, 95% CI: -2.66 to 4.29, p=0.65).

  The MELD score (3 RCT’s) was significantly lower (MD= -2.55, 95% CI: -3.56 to – 1.54, p<0.00001).

  MHE reversal rate was higher in the probiotic group (RR=2.79, 95% CI: 1.23 to 6.35, p=0.01).

• Fixed-effects model:

  OHE incidence (7 RCTs) was lower with probiotics (RR = 0.18, 95% CI: 0.09 to 0.34, p<0.00001).

Conclusion

• Probiotics are associated with improvements in MHE, including reduced blood ammonia levels and enhanced cognitive function.

• Patients with a history of cirrhosis and who have been diagnosed with MHE would benefit from including probiotics in their supplement plan.

• If a patient with MHE is being treated with medications like lactulose or rifaximin, practitioners should highlight the benefits that probiotics could have on MHE incase their general practitioner needs to make adjusments to their medication.

• The majority of studies used in the paper were trials from China (12), which may bias results pointing for future research to include more countries.

• The RCTs showed significant heterogeneity in certain areas like ALT, DST score, NCT reaction times and MHE remission rates. Additional studies would benefit from adopting standardised protocols including clearly defined probiotic strains, dosages and length of treatment.

• Including more databases to capture further RCT’s missed in this study will help to increase confidence in results.

• Larger, high quality RCT’s are needed to confirm the effect of probiotics on MHE.