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      Effects of Synbiotics, Probiotics, and Prebiotics on Liver Enzymes of Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis

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          Abstract

          Background

          A systematic review and network meta-analysis was primarily conducted to compare the effects of synbiotics, probiotics, and prebiotics on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, their effects on body mass index (BMI), waist circumference (WC), lipid profile, fasting blood sugar (FBS), and homeostatic model assessment-insulin resistance (HOMA-IR) of patients with non-alcoholic fatty liver disease (NAFLD) were investigated and analyzed as secondary outcomes.

          Methods

          The randomized controlled trials (RCTs), limited to the English language, were searched through PubMed, the Web of Science, Embase, CLINAHL Plus, and the Cochrane Library from inception to February 2, 2022. The eligible studies were reviewed and their risk-of-bias and heterogeneity were assessed. Both direct and indirect evidence were assembled using a random-effects model. The effects of the intervention were presented as weighted mean differences (WMD) with 95% confidence interval (95% CI).

          Results

          Of 3,864 identified records, a total of 1,389 patients with NAFLD from 26 RCTs were included in the analyses. Among these, 241 were diagnosed with non-alcoholic steatohepatitis. The quality assessment reported a moderate risk of bias from most studies. Among adult patients with NAFLD, when compared with placebo, synbiotics provided the largest effect on reductions of AST (−12.71 IU/L; 95% CI: −16.95, −8.47), WC (−2.26 cm; 95% CI: −2.98, −1.54), total cholesterol (−22.23 mg/dl; 95% CI: −29.55, −14.90), low-density lipoproteins (−17.72 mg/dl; 95% CI: −25.23, −10.22), and FBS (−6.75 mg/dl; 95% CI: −10.67, −2.84). Probiotics lowered ALT (−14.46 IU/L; 95% CI: −21.33, −7.59) and triglycerides (−20.97 mg/dl; 95% CI: −40.42, −1.53) the most. None had significant impact on BMI, high-density lipoproteins, and HOMA-IR changes.

          Conclusion

          Synbiotics and probiotics are likely to be the most potential effective treatments for AST and ALT reduction in adult patients with NAFLD, respectively. Although liver enzymes cannot exactly define the severity of NAFLD, unlike the results from biopsy or imaging tests, they are important indicators that can monitor the status of the disease and provide benefits for clinical management.

          Systematic Review Registration

          [ https://www.crd.york.ac.uk/prospero/display_reco rd.php?ID], identifier [CRD42020200301].

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          Most cited references50

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          Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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            The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

            The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.
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              • Article: not found

              The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                20 May 2022
                2022
                : 9
                : 880014
                Affiliations
                [1] 1Unit of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao , Phayao, Thailand
                [2] 2Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao , Phayao, Thailand
                [3] 3Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao , Phayao, Thailand
                [4] 4Division of Clinical Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao , Phayao, Thailand
                [5] 5Division of Pharmaceutical Care, Department of Pharmacy, Phrae Hospital , Phrae, Thailand
                [6] 6Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand
                [7] 7Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City , UT, United States
                [8] 8IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City , UT, United States
                [9] 9Division of Social and Administrative Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao , Phayao, Thailand
                Author notes

                Edited by: Pietro Vajro, University of Salerno, Italy

                Reviewed by: Anna Alisi, Bambino Gesù Children’s Hospital (IRCCS), Italy; Michele Malaguarnera, Principe Felipe Research Center (CIPF), Spain

                *Correspondence: Surasak Saokaew, surasak.sa@ 123456up.ac.th
                Pochamana Phisalprapa, coco_a105@ 123456hotmail.com

                ORCID: Sukrit Kanchanasurakit, orcid.org/0000-0002-1268-2665; Chayanis Kositamongkol, orcid.org/0000-0001-7182-0733; Monnaree Nunta, orcid.org/0000-0003-1243-7798; Nathorn Chaiyakunapruk, orcid.org/0000-0003-4572-8794; Surasak Saokaew, orcid.org/0000-0002-1382-0660; Pochamana Phisalprapa, orcid.org/0000-0003-1995-4405

                This article was submitted to Nutritional Epidemiology, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2022.880014
                9167056
                35669067
                a935d6bf-664c-48eb-9ea3-7a493e4af7da
                Copyright © 2022 Kanchanasurakit, Kositamongkol, Lanoi, Nunta, Saetuan, Chaiyakunapruk, Saokaew and Phisalprapa.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 February 2022
                : 13 April 2022
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 50, Pages: 13, Words: 8254
                Funding
                Funded by: University of Phayao, doi 10.13039/501100011093;
                Award ID: FF65-UoE005
                Categories
                Nutrition
                Systematic Review

                non-alcoholic fatty liver disease (nafld),non-alcoholic steatohepatitis (nash),meta-analysis,synbiotic,probiotic,prebiotic,liver enzymes

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