RESUMEN
BACKGROUND: The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease (NAFLD). Hence, we performed a double-blind single center randomized placebo-controlled trial (RCT) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD. METHODS: A total of 48 patients met the criteria for inclusion. They were randomly assigned to receive "Symbiter Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in transaminases level, serum lipids and cytokines levels. RESULTS: In probiotic-omega group, FLI significantly decreased from 83.53±2.60 to 76.26±2.96 (P<0.001) while no significant changes were observed in the placebo group (82.86±2.45 to 81.09±2.84; P=0.156). Changes of LS in both groups were insignificant. Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase, triglycerides, and total cholesterol. Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group: IL-1ß (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). CONCLUSIONS: Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat, improve serum lipids, metabolic profile, and reduce chronic systemic inflammatory state.
Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/terapia , Probióticos/uso terapéutico , Adulto , Anciano , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Probiotics have a beneficial effect on nonalcoholic fatty liver disease (NAFLD) in animal models. Randomized placebo-controlled trials (RCTs) in NAFLD are still lacking in humans despite a large number of data from animal research. AIM: We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD. METHODS: A total of 58 patients met the criteria for inclusion. They were randomly assigned to receive the multi-probiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. The primary main outcomes were the changes in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in aminotransferase activity, serum lipids and cytokines (TNF-α, IL-1ß, IL-6, IL-8, and IFN-γ) levels. Analysis of covariance was used to assess the difference between groups. RESULTS: In the probiotic group, FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 (p<0.001) but it did not change in the placebo group (82.57+/-2.45 to 81.6 +/-2.36; p=0.367). In both groups a slight but not significant reduction of LS measured by SWE was detected. Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT. Among the markers of chronic systemic inflammatory state, only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic. CONCLUSION: The probiotic "Symbiter" reduces liver fat, aminotransferase activity, and the TNF-α and IL-6 levels in NAFLD patients. Modulation of the gut microbiota might represent a new therapy for NAFLD, which should be tested in larger studies.
Asunto(s)
Citocinas/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Probióticos , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Diagnóstico por Imagen de Elasticidad , Humanos , Interleucina-6/sangre , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Factor de Necrosis Tumoral alfa/sangre , gamma-Glutamiltransferasa/sangreRESUMEN
Liver biopsy due to the limitations is not recommended for all patients with suspected Alcoholic Liver Disease (ALD) but useful for establishing the stage and severity of ALD, in case of aggressive forms or severe steatohepatitis requiring specific therapies, for distinguishing comorbid liver pathology. Procedure is invasive and that's why associated with some potential adverse effects and complications which may be minor (pain or vagal reactions, transient hypotension) or major such as visceral perforation, bile peritonitis or significant bleeding. The typical histological features in patients with ALD include steatosis, hepatocellular damage (ballooning and/or Mallory-Denk bodies), lobular inflammation with basically polymorphonuclear cells infiltration, with a variable degree of fibrosis and lobular distortion that may progress to cirrhosis which confers a high risk of complications (ascites, variceal bleeding, hepatic encephalopathy, renal failure and bacterial infections).