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THE THERAPEUTIC IMPACT OF PROBIOTICS ON NONALCOHOLIC FATTY LIVER DISEASE IN PEDIATRICS: A SYSTEMATIC REVIEW.

ABSTRACT: OBJECTIVE:Evaluate the effects of probiotics use, compared with placebo, in pediatric patients with non-alcoholic fatty liver disease (NAFLD), using laboratorial and ultrasonographic parameters as outcomes. METHODS:A systematic review of the literature was performed through MEDLINE and Lilacs databases. The articles selected were randomized controlled clinical trials published until November 2018, without any language restriction, dealing with pediatric patients with NAFLD. Patients were divided into 2 groups. One group received probiotic therapy and the other group, only received placebo. The primary outcome evaluated was the difference between the serum levels of alanine aminotransferase (ALT) before and after receiving probiotics or placebo. The secondary outcomes evaluated were the serum aspartate aminotransferase levels, body mass index, serum triglycerides, waist circumference and level of liver steatosis on the ultrasonography. RESULTS:A total of 46 articles were recovered, and 3 articles were included in the qualitative analysis, totaling 128 patients. Two trials revealed a significant decrease of alanine aminotransferase levels after treatment with probiotics (Lactobacillus rhamnosus for 8 weeks; Bifidobacterium+Lactobacillus for 12 weeks), when compared to the placebo. The other variables did not show a statistically significant difference between both groups. CONCLUSIONS:Probiotic therapy has contributed to the reduction of ALT serum levels in pediatric patients with nonalcoholic fatty liver disease, which is in line with results found by other authors in scientific literature. Regarding the secondary outcomes, the use of probiotics did not show benefits or damages compared to placebo.

SUBMITTER: Chaves FGB

PROVIDER: S-EPMC7450687 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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THE THERAPEUTIC IMPACT OF PROBIOTICS ON NONALCOHOLIC FATTY LIVER DISEASE IN PEDIATRICS: A SYSTEMATIC REVIEW.

Chaves Felipe Galvão Batista FGB Oliveira Glauco Ferreira de GF Ribeiro João Paulo JP Serafim João Victor JV Cordeiro Luiz Felipe Medeiros LFM Alvares Matheus Alves MA Cecchi Marcelo Trindade MT Vasquez Murilo Cordeiro MC Souza Thaísy Bianka Dorta de TBD Rullo Vera Esteves Vagnozzi VEV

Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo 20200826

<h4>Objective</h4>Evaluate the effects of probiotics use, compared with placebo, in pediatric patients with non-alcoholic fatty liver disease (NAFLD), using laboratorial and ultrasonographic parameters as outcomes.<h4>Methods</h4>A systematic review of the literature was performed through MEDLINE and Lilacs databases. The articles selected were randomized controlled clinical trials published until November 2018, without any language restriction, dealing with pediatric patients with NAFLD. Patien ...[more]

PMID: 32876312

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Project description:BACKGROUND:Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD. METHODS:We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications. RESULTS:We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight. CONCLUSIONS:Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.

Project description:Individuals with nonalcoholic fatty liver disease (NAFLD) are characterized by increased cardiovascular risk. Endothelial dysfunction, a mechanism implicated in those processes, may constitute the missing link in this interaction. Therefore, this systematic review and meta-analysis aims to evaluate the association of endothelial dysfunction, assessed by flow-mediated dilation (FMD) of the brachial artery, with NAFLD. We conducted a systematic literature search for studies assessing the difference in FMD between patients with NAFLD and controls. Exclusion criteria consisted of preclinical studies, studies in children/adolescents, no FMD assessment, and the absence of an NAFLD/control group. The database search identified 96 studies. Following the application of the exclusion criteria, 22 studies were included in the meta-analysis (NAFLD: 2164 subjects; control: 3322 subjects). Compared with controls, patients with NAFLD had significantly lower FMD% values (SMD: -1.37, 95% CI -1.91 to -0.83, p < 0.001, I2: 98%). Results remained unaffected after exclusion of any single study. Subgroup analysis revealed significantly decreased FMD in NAFLD subjects diagnosed with liver ultrasound or liver biopsy compared with method combination or other methods, while no differences were observed according to the chosen cuff inflation threshold, the presence of a significant difference in obesity measures between the groups, or the type of the control group (age- and sex-matched vs. other). Funnel plot asymmetry was not observed. Finally, compared with patients with pure steatosis, individuals with nonalcoholic steatohepatitis had significantly lower FMD (SMD: -0.81, 95% CI -1.51 to -0.31, p = 0.003, I2: 81%). In conclusion, FMD of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in subjects with nonalcoholic fatty liver disease. Patients with nonalcoholic steatohepatitis might be facing a more pronounced endothelial impairment.

Project description:Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The gut-derived endotoxin plays an essential role in the pathophysiological development and progression of NAFLD. By using rat models of choline-deficient/L-amino acid-defined (CDAA)-diet-induced NAFLD, we examined whether MIYAIRI 588--a butyrate-producing probiotic--prevents the progression of pathophysiological changes from steatosis to hepatocarcinogenesis. In vivo experiments showed that treatment with MIYAIRI 588 reduced CDAA-diet-induced hepatic lipid deposition and significantly improved the triglyceride content, insulin resistance, serum endotoxin levels, and hepatic inflammatory indexes. We also found that MIYAIRI 588 substantially increased the activation of hepatic adenosine 5'-monophosphate-activated protein kinase (AMPK) and AKT and the expression of lipogenesis- or lipolysis-related proteins. MIYAIRI 588 also improved CDAA-diet-induced delocalization and substantially decreased the expression of the tight-junction proteins intestinal zonula occluden-1 and occludin in CDAA-diet-fed rats. Further, the MIYAIRI 588-treated rats also showed remarkable induction of nuclear factor erythoid 2-related factor 2 (Nrf2) and its targeted antioxidative enzymes, which suppressed hepatic oxidative stress. In vitro studies revealed that treatment with sodium butyrate (NaB) also activated AMPK and AKT and enhanced Nrf2 expression by precluding ubiquitination, thereby increasing the half-life of the Nrf2 protein. Pharmacological studies and siRNA knockdown experiments showed that NaB-mediated AMPK activation induced the phosphorylation and nuclear translocation of Sirtuin 1, leading to the increased assembly of mammalian TOR complex 2 and phosphorylation of AKT at Ser473 and subsequent induction of Nrf2 expression and activation. These favorable changes caused an obvious decrease in hepatic fibrous deposition, GST-P-positive foci development, and hepatocarcinogenesis. Our data clearly established that the probiotic MIYAIRI 588 has beneficial effects in the prevention of NAFLD progression.

Dataset Information

THE THERAPEUTIC IMPACT OF PROBIOTICS ON NONALCOHOLIC FATTY LIVER DISEASE IN PEDIATRICS: A SYSTEMATIC REVIEW.

Publications

THE THERAPEUTIC IMPACT OF PROBIOTICS ON NONALCOHOLIC FATTY LIVER DISEASE IN PEDIATRICS: A SYSTEMATIC REVIEW.

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