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Biopsy-proven NAFLD (biopsy-proven + nafld)
Selected AbstractsIncreased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease,HEPATOLOGY, Issue 6 2009Luca Miele The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut-derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy-proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of 51Cr-ethylene diamine tetraacetate (51Cr-EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 (ZO-1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. Conclusions: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition. (HEPATOLOGY 2009.) [source] Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010M. Estep Aliment Pharmacol Ther 2010; 32: 487,497 Summary Background, Progression of non-alcoholic fatty liver disease (NAFLD) can be facilitated by soluble molecules secreted by visceral adipose tissue (VAT). MicroRNAs (miRNAs) are likely to regulate some of these molecular pathways involved in pathogenesis of NAFLD. Aim, To profile miRNA expression in the visceral adipose tissue of patients with NAFLD. Methods, Visceral adipose tissue samples were collected from NAFLD patients and frozen. Patients with biopsy-proven NAFLD were divided into non-alcoholic steatohepatitis (NASH) (n = 12) and non-NASH (n = 12) cohorts controlled for clinical and demographic characteristics. Extracted total RNA was profiled using TaqMan Human MicroRNA arrays. Univariate Mann,Whitney comparisons and multivariate regression analysis were performed to compare miRNA profiles. Results, A total of 113 miRNA differentially expressed between NASH patients and non-NASH patients (P < 0.05). Of these, seven remained significant after multiple test correction (hsa-miR-132, hsa-miR-150, hsa-miR-433, hsa-miR-28-3p, hsa-miR-511, hsa-miR-517a, hsa-miR-671). Predicted target genes for these miRNAs include insulin receptor pathway components (IGF1, IGFR13), cytokines (CCL3, IL6), ghrelin/obestatin gene, and inflammation-related genes (NFKB1, RELB, FAS). In addition, two miRNA species, hsa-miR-197 and hsa-miR-99, were significantly associated with pericellular fibrosis in NASH patients (P < 0.05). Levels of IL-6 in the serum negatively correlated with the expression levels of all seven miRNAs capable of down regulating IL-6 encoding gene. Conclusions, miRNA expression from VAT may contribute to the pathogenesis of NAFLD , a finding which may distinguish relatively simple steatosis from NASH. This could help identify potential targets for pharmacological treatment regimens and candidate biomarkers for NASH. [source] Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010K. D. KISTLER Aliment Pharmacol Ther,31, 396,406 Summary Background, Data on the quality of life (QOL) of children with non-alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD. Aim, To characterize QOL and symptoms of children with NAFLD and to compare QOL in children with NAFLD with that in a sample of healthy children. Methods, Quality of life and symptoms were assessed in children with biopsy-proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores were compared with scores from healthy children. For children with NAFLD, between-group comparisons were made to test associations of demography, histological severity, symptoms and QOL. Results, A total of 239 children (mean age 12.6 years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P < 0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9, P < 0.01) scores compared with healthy children. QOL scores did not significantly differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness accounted for almost half of the variance in QOL scores. Impaired QOL was present in 39% of children with NAFLD. Conclusions, Children with NAFLD have a decrement in QOL. Symptoms were a major determinant of this impairment. Interventions are needed to restore and optimize QOL in children with NAFLD. [source] Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009E. VILAR GOMEZ Summary Background, Nonalcoholic fatty liver disease (NAFLD) is a significant health problem for which there is no universally accepted pharmacological treatment. The combination of weight loss and antioxidant drugs to ameliorate insulin resistance and improve steatosis, inflammation and fibrosis provides the rational for therapeutic trials. Aim, To evaluate the efficacy and safety of a nutritional supplement Viusid in association with diet and exercise for NAFLD. Methods, A randomized, controlled and parallel-group trial was conducted at a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). We randomly assigned 60 patients with liver biopsy-proven NAFLD to 6 months of treatment with a hypocaloric diet plus aerobic exercise daily and three Viusid sachets daily or a hypocaloric diet and exercise. Endpoints were improvement in the NAFLD activity score (NAS), fibrosis and normalization of serum aminotransferase levels. Results, A significant improvement in steatosis, necroinflammation and fibrosis was seen in each group of treatment (P < 0.01 for each feature). The Viusid group, as compared with the control group, significantly reduced the mean of NAS [from 4.18 to 0.54 points in the Viusid group vs. 4.45 to 2.2 points in the control group (P < 0.001)]. On between-group comparison, Viusid was found to be associated with a significantly greater improvement in steatosis (P < 0.001), ballooning (P = 0.002) and lobular inflammation (P = 0.025), but not in fibrosis (P = 0.07). Viusid was well tolerated. Conclusions, Our results indicate that treatment with diet and exercise leads to a notable improvement in the histological features of NAFLD; however, the administration of Viusid intensifies the improvements of histological findings, especially of steatosis and inflammation. [source] Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levelsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009V. W.-S. Summary Background, Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear. Aim, To evaluate the metabolic and histological features of NAFLD patients with different ALT levels. Methods, A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared. Results, Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis. Discussion, Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level. [source] | ||||||||||