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The promising role of probiotic and synbiotic therapy in aminotransferase levels and inflammatory markers in patients with nonalcoholic fatty liver disease – a systematic review and meta-analysis

Khan, Muhammad Y.a; Mihali, Albana B.a; Rawala, Muhammad S.b; Aslam, Ayshac; Siddiqui, Waqas J.d

European Journal of Gastroenterology & Hepatology: June 2019 - Volume 31 - Issue 6 - p 703–715
doi: 10.1097/MEG.0000000000001371
Original Articles: Hepatology

Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. The pathogenesis of NAFLD is complex and multifactorial. There is growing evidence that altered gut microbiota plays a key role in NAFLD progression. Probiotics/synbiotics, by modifying gut microbiota, may be a promising treatment choice for NAFLD management.

Aim The aim of this study was to study the effect of probiotics/synbiotics on various laboratory and radiographic parameters in NAFLD management.

Materials and methods A systematic review and meta-analysis were carried out according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We searched PubMed, Medline, and Google Scholar for randomized-controlled trials that studied the role of probiotics/synbiotics in NAFLD. The primary outcome was change in baseline alanine aminotransferase and aspartate aminotransferase in the treatment arm. We used a random-effects model and inverse variance for the continuous data to estimate the mean difference (MD) and the standard mean difference (SMD) in RevMan Version 5.3.

Results We included 12 randomized-controlled trials for analysis. The intervention arm, which comprised of the probiotic and/or the synbiotic arm, showed a significant improvement in alanine aminotransferase levels, MD=–13.93, confidence interval (CI)=–20.20 to –7.66, P value of less than 0.0001, I2=92% and aspartate aminotransferase levels MD=−11.45, CI=−15.15 to −7.74, P value of less than 0.00001, I2=91%. There was a reduction in high-sensitivity C-reactive protein levels in the intervention arm, SMD=–0.68, CI=–1.10 to –0.26, P value of 0.001, I2=0%. The liver fibrosis score improved in the intervention arm, MD=–0.71, CI=–0.81 to –0.61, P value less than 0.00001, I2=0%.

Conclusion Probiotic/synbiotic use improves aminotransaminase levels and reduces proinflammatory marker high-sensitivity C-reactive protein and liver fibrosis in NAFLD patients.

aDepartment of Medicine, Capital Health Regional Medical Center, Trenton, New Jersey

bDepartment of Medicine, Rapides Regional Medical Center, Alexandria, Louisiana

cDepartment of Medicine, Louis A Weiss Memorial Hospital, Chicago, Illinois

dDepartment of Medicine, Orange Park Medical Center, Orange Park, Florida, USA

Correspondence to Muhammad Y. Khan, MD, 750 Brunswick Ave, Trenton 08638, New Jersey, USA Tel: +1 609 394 6031; fax: +1 609 815 7178; e-mail:

Received December 4, 2018

Accepted January 8, 2019

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