Non-alcoholic Steatohepatitis: Comparison of Intestinal Microbiota between Different Metabolic Profiles. A Pilot Study.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) has multifactorial etiopathogenesis, and intestinal microbiota is co-responsible in this process. The aim of this study was to evaluate the intestinal microbiota in NASH patients with different metabolic profiles. METHODS: Patients with biopsy-proven NASH were evaluated. Subjects were divided into two groups according to their metabolic profile, with or without metabolic syndrome (MS). Their characteristics in relation to liver disease and intestinal microbiota were analyzed. To evaluate the microbiota, breath tests to investigate small intestinal bacterial overgrowth (SIBO) and fecal microbiota analysis by fluorescence in situ hybridization (FISH) were performed. RESULTS: There was a high prevalence of SIBO in both groups, with no significant difference between them. Breathing tests were positive in 43.8% of patients with MS and 50% of those without MS. There was a significant difference regarding the quantification of Verrucomicrobiales, less abundant in patients with NASH without MS. Its lower concentration also correlated with higher serum ferritin levels and higher hepatocyte ballooning. This order of bacteria, through its representative in human microbiota, Akkermansia muciniphila, is associated with mucosal protection and metabolic processes with liver aggression. CONCLUSIONS: Our results suggested that lower Verrucomicrobiales concentration is associated with higher inflammatory activity in patients with NASH without MS, where the disease etiopathogenesis does not have its classic metabolic substrate.

Effects of Dietary Intervention on Gut Microbiota and Metabolic-Nutritional Profile of Outpatients with Non-Alcoholic Steatohepatitis: a Randomized Clinical Trial.

BACKGROUND AND AIMS: Modulation of the gut microbiota emerges as a therapeutic possibility to improve health. Our objective was to compare the impact of three months of intervention with diet plus nutritional orientation versus only nutritional orientation on the gut microbiota and metabolic-nutritional profile of outpatients with non-alcoholic steatohepatitis. METHODS: It was a randomized clinical trial with 40 outpatients (49.48 ± 10.3 years), allocated in two groups: DIET group (n=20), who received diet (1.651.34 ± 263.25 kcal; 47% carbohydrates, 28% lipids, 25% proteins, 30 g fibers) and nutritional orientation, and control group (n = 20), which received only nutritional orientation. RESULTS: The DIET group, in relation to baseline, presented a reduction in body weight (p<0.001), BMI (p<0.001), waist circumference (p=0.001), percentage of fat (p=0.002), serum aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p=0.001), glycemia (p=0.003), homeostasis model assessment of insulin resistance (p=0.017), total cholesterol (p=0.014), and triacylglycerols (p=0.008), whereas the control group did not present changes. After intervention, the small intestinal bacterial overgrowth frequency was 30% in the DIET group and 45% in the control group (p=0.327). In the DIET group, an increase in the density of total microorganisms (3.76 ± 7.17 x 10 8 cells g -1 ; p=0.048) was detected, while in the control group reduced Bacteroidetes (-0.77 ± 2.01 x 10 8 cells g -1 , p=0.044) and Verrucomicrobiales (-0.46 ± 0.75 x 10 8 cells g -1 ; p=0.022) were observed. CONCLUSIONS: The results suggest that exclusively dietary modifications contribute to health promotion in non-alcoholic steatohepatitis and should be the basis of nutritional treatment for this condition.

Association between dietary total antioxidant capacity and hepatocellular ballooning in nonalcoholic steatohepatitis: a cross-sectional study.

PURPOSE: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, ballooning, and in some cases, fibrosis, which can progress to cirrhosis and carcinoma. The progression of NASH is closely related to oxidative stress. Dietary intake of antioxidants has been suggested in protection against oxidative damage and related clinical complications. Thus, we evaluated the potential association of dietary total antioxidant capacity (TAC) with disease severity in NASH patients, as well as with anthropometric and body composition markers and biochemical parameters. METHODS: Thirty-three outpatients with a mean age of 48.4 ± 1.9 years were evaluated. Dietary TAC was estimated from a quantitative food frequency questionnaire. NASH severity, determined by liver biopsy, lifestyle characteristics, occurrence of comorbidities, anthropometry, body composition, and biochemical parameters were assessed. RESULTS: NASH patients who had a higher dietary TAC had fewer ballooned hepatocytes compared to those with a lower TAC (p = 0.024). The patients with the highest dietary TAC had a reduction of approximately 20% in the risk of having many ballooned hepatocytes (OR 0.791; 95% CI 0.643-0.974; p = 0.027). There was no association of steatosis, lobular inflammation, and fibrosis with dietary TAC. The same occurred for lifestyle characteristics, occurrence of comorbidities, anthropometry, body composition, and biochemical parameters. CONCLUSION: Dietary TAC is higher in patients with lower hepatic injury (ballooning), suggesting a possible role of food intake naturally high in its antioxidant capacity in reducing free radical production and, consequently, oxidative stress.

Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis.

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gut microbiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gut microbiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. RESULT: The available literature has proposed mechanisms for an association between gut microbiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gut microbiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. CONCLUSION: Although few studies have evaluated the composition of the gut microbiota in patients with NASH, it is observed that these individuals have a distinct gut microbiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gut microbiota through diet control offers new challenges for future studies.

Arthritis, eosinophilia, and autoimmune liver disease: a diagnostic challenge.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown etiology. It is composed of immune-mediated liver injury and significant immunological aspects. Arthritis can be observed in patients with AIH before recognition of the disease, which can lead to a diagnostic challenge. Although there are few reported cases in literature, peripheral blood eosinophilia might also play a part in such diagnosis. We report an intriguing case of a 41-year-old man who presented to our service with arthritis and eosinophilia as initial manifestations and was eventually diagnosed with overlap syndrome: AIH and primary sclerosing cholangitis. The present report aims to include eosinophilia among the clinical features of AIH, highlighting the possibility of its detection before the onset of either articular or hepatic disturbances.