Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice.

Distribution of persistent organic pollutants in two different fat compartments from obese individuals.

There are only few studies defining persistent organic pollutant (POP) concentrations in various fat compartments from living obese individuals. The present study has therefore determined the concentrations of various classes of organohalogenated compounds, such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in visceral fat (VF: n=52) and subcutaneous abdominal fat (SF: n=52) samples collected in 2010-2012 from obese individuals in Belgium. Organohalogen compounds were detected in all fat samples in the decreasing order of their concentrations: PCBs>DDTs>HCHs>CHLs>HCB>HBCDs>PBDEs, suggesting that Belgians have been widely exposed to these contaminants. The levels and the patterns of POP distribution in VF and SF tissue depots were not significantly different. Concentrations of PCBs (VF/SF; median: 285/275ng/g lw) and DDTs (VF/SF; median: 150/155ng/g lw) were the major POPs in all fat samples. Concerning PCBs, PCB 153 (VF/SF: 27/26%) was the most dominant congener, followed by PCB 180 (VF/SF: 17/18%), PCB 138 (VF/SF: 15/14.5%) and PCB 170 (VF/SF: 8.1/8.4%) to the sum PCBs, respectively. Levels of HBCDs (VF/SF; median: 4.0/3.7ng/g lw) and PBDEs (VF/SF; median: 2.6/2.7ng/g lw) were 1-2 orders of magnitude lower than those of PCBs and DDTs. Among PBDEs, BDE 153 (VF/SF: 31/34%) was the dominant congener, followed by BDE 47 (VF/SF: 26/23%), BDE 154 (VF/SF: 16/16%), BDE 100 (VF/SF: 10/11%) and BDE 99 (VF/SF: 9/9%). To our knowledge, this is the first report on HBCD concentrations in Belgian human fat tissues. Total PBDE and HBCD levels in human fat samples could not be correlated with age. In agreement with the literature, a significant correlation (p<0.05) between age and the concentration of PCBs (r=0.828), DDTs (r=0.640), HCHs (r=0.666), CHLs (r=0.534) and HCB (r=0.754), was observed in the present study. Levels of DDTs, HCHs, HCB and CHLs were also significantly correlated to each other, suggesting that they share similar exposure routes. Correlation with computed tomography (CT) scan data revealed that VF and VF/SF ratios are positive for most of the POPs, such as PCBs, PBDEs, p,p'DDE, CHLs, ß-HCH, and HCB. To our knowledge, this study is the first to assess the relationship between POP levels in adipose tissue and markers of abdominal adiposity, determined by CT.

N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease is a spectrum of disorders ranging from steatosis to non-alcoholic steatohepatitis (NASH). Steatosis of the liver is benign, whereas NASH can progress to cirrhosis or even hepatocellular carcinoma. Currently, a liver biopsy is the only validated method to distinct NASH from steatosis. AIM: The objective of this study was to identify a biomarker specific for NASH based on the N-glycosylation of serum proteins. METHODS: N-glycosylation patterns were assessed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS: Initially, a glycomarker (log[NGA2F]/[NA2]) was developed based on the results obtained in 51 obese non-alcoholic patients scheduled for bariatric surgery. Multivariate analysis showed that our glycomarker had the lowest P-value of all biomarkers in distinguishing NASH from steatosis (P=0.069). The glycomarker was validated in a cohort of 224 non-alcoholic fatty liver disease patients. In both pilot and validation study, glycomarker score increased in ascending amount of lobular inflammation (single-factor ANOVA, P ≤ 0.001 and P=0.012, respectively). The N-glycan profile of immunoglobulin G in the NASH population confirmed the significantly increased undergalactosylation present in these patients. CONCLUSION: Our glycomarker specifically recognises liver inflammation in obese individuals which is the main trigger for the development of steatohepatitis and can differentiate between steatosis and NASH.

Sleep-disordered breathing: a new risk factor of suspected fatty liver disease in overweight children and adolescents?

INTRODUCTION: The aim of this retrospective study was to investigate if sleep-disordered breathing (SDB) was an independent predictor of suspected fatty liver disease in a clinical sample of overweight children and adolescents. MATERIALS AND METHODS: Consecutive overweight and obese children attending a pediatric obesity clinic underwent polysomnography, fasting blood sample, and abdominal ultrasound. RESULTS AND DISCUSSION: The respiratory disturbance index, percentage of total sleep time with SO2 < 90%, and SaO2nadir were associated with higher alanine amino-transferases (ALT) independent of abdominal obesity. Multiple logistic regression selected waist circumference (odds ratio = 1.05; p = 0.05) and SaO2nadir (odds ratio = 0.87; p = 0.03) as predictors of suggestive fatty liver disease, defined as ALT > 40 U/L and/or hyperechoic liver on abdominal ultrasound. This study supports the association between the severity of SDB and suspected fatty liver disease in a clinical sample of overweight children and adolescents. We recommend more research on the influence of SDB on the development of fatty liver disease and on the effect of treating sleep apnea on liver function parameters.

Tolerability of sibutramine during a 6-week treatment period in high-risk patients with cardiovascular disease and/or diabetes: a preliminary analysis of the Sibutramine Cardiovascular Outcomes (SCOUT) Trial.

Uncertainties about the cardiovascular safety of sibutramine led to the SCOUT trial that is investigating sibutramine plus weight management in high-risk, overweight/obese patients. A 6-week lead-in period during which all patients received sibutramine permitted an initial assessment of tolerability. A total of 10,742 patients received sibutramine and 3.1% of these discontinued due to an adverse event; issues affecting more than 10 patients were drug intolerance, headache, insomnia, nausea, dry mouth, and constipation-, tachycardia-, and hypertension-related events. Serious adverse events, most commonly associated with the System Organ Class, Cardiac disorders, were reported by 2.7% of patients; however, the majority was not considered sibutramine-related. Adverse events relating to high blood pressure and/or pulse rate, whether reported as adverse events leading to discontinuation, or serious adverse events were reported by less than 0.2% of patients. No serious or individual events leading to discontinuation occurred in more than 25 patients. There were 15 (0.1%) deaths; 10 were attributed to a cardiovascular cause. Discontinuations for adverse events were lower than anticipated. Serious adverse events generally reflected sibutramine's known pharmacology or were related to cardiac disorders already present in this high-risk population. When compared with epidemiological data, overall mortality rate was low and sibutramine was well tolerated in this mainly off-label population. No new safety issues were detected.