Objective Pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD.
Methods Thirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile.
Results Thirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study.
Conclusion Patients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines.
Trial registration number The clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI); http://ctri.nic.in, No. CTRI/2008/091/000074
- non-alcoholic steatohepatitis
- hepatic steatosis
- fatty liver
- metabolic syndrome
- bacterial overgrowth
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Presented at Data presented by Prof. Ajay Duseja, as a poster at the AASLD Liver Meeting on Nov 12, 2016 [Abstract ID 1185, Hepatology 2016; 64(Suppl S1):596A].
Contributors AD and SKA contributed towards the conception and design of the study, recruited subjects, monitored the conduct and progress of the study, interpreted the results, drafted and reviewed the manuscript. RKD and YC assisted with the study design, subject enrolments, interpretation of results and critical review of the manuscript. MM, SC and S were responsible for management and coordination of the trial, monitoring the study progress, data collection and its entry in database files and drafting of the manuscript. SR, AD and SDG performed laboratory investigations and histopathological assessments, analysed and interpreted the data, and critically reviewed the manuscript. All the authors have read and have approved the final manuscript.
Funding CD Pharma India Private Limited (New Delhi, India) funded the study and supplied the investigational drugs but did not participate in any part of the study.
Disclaimer The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to CONSORT 2010 Statement.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by Institutional Ethics Committee of both hospitals (AIIMS: Ref. No. A-49 and PGIMER: Micro/2007/2582) and was conducted in conformance to ethical guidelines of the 1975 Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on request to researchers who provide a methodically sound proposal and whose proposed use of the data has been approved by an independent review committee identified for this purpose. Such proposals may be directed to the corresponding author (firstname.lastname@example.org). However, to gain access, data requestors will need to sign and submit a cover letter mentioning the purpose with a list of requested documents along with a statement/undertaking to maintain data confidentiality.
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