BACKGROUND & AIMS: The prevalence of nonalcoholic steatohepatitis (NASH) associated hepatocellular carcinoma (HCC) is increasing. However, strategies for detection of early-stage HCC in patients with NASH have limitations. We assessed the ability of the GALAD score, which determines risk of HCC based on patient sex; age; and serum levels of a-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP), to detect HCC in patients with NASH. METHODS: We performed a case-control study of 125 patients with HCC (20% within Milan Criteria) and 231 patients without HCC (NASH controls) from 8 centers in Germany. We compared the performance of serum AFP, AFP-L3, or DCP vs GALAD score to identify patients with HCC using receiver operating characteristic curves and corresponding area under the curve (AUC) analyses. We also analyzed data from 389 patients with NASH under surveillance for HCC in Japan, followed for a median of 167 months. During the 5-year screening period, 26 patients developed HCC. To compensate for irregular intervals of data points, we performed locally weighted scatterplot smoothing, linear regression, and a non-linear curve fit to assess development of GALAD before HCC development. RESULTS: The GALAD score identified patients with any stage HCC with an AUC of 0.96significantly greater than values for serum levels of AFP (AUC, 0.88), AFP-L3 (AUC, 0.86) or DCP (AUC, 0.87).

Brominated flame retardants (BFRs) are synthetic additives mainly used in electrical and electronic appliances and in construction materials. The properties of some BFRs are typical for persistent organic pollutants, and certain BFRs, in particular some polybrominated diphenyl ether (PBDE) congeners and hexabromocyclododecane (HBCD), are suspected to cause adverse health effects. Global consumption of the most demanded BFRs, i.e., penta-, octa-, and decaBDE, tetrabromobisphenol A (TBBPA), and HBCD, has doubled in the 1990s. Only limited and rather uncertain data are available regarding the occurrence of BFRs in consumer goods and waste fractions as well as regarding emissions during use and disposal. The knowledge of anthropogenic substance flows and stocks is essential for early recognition of environmental impacts and effective chemicals management. In this paper, actual levels of penta-, octa-, and decaBDE, TBBPA, and HBCD in waste electrical and electronic equipment (WEEE) as a major carrier of BFRs are presented. These BFRs have been determined in products of a modern Swiss recycling plant applying gas chromatography/electron capture detection and gas chromatography/mass spectrometry analysis. A substance flow analysis (SFA) technique has been used to characterize the flows of target substances in the recycling process from the bulk WEEE input into the output products. Average concentrations in small size WEEE, representing the relevant electric and electronic appliances in WEEE, sampled in 2003 amounted to 34 mg/kg for pentaBDE, 530 mg/kg for octaBDE, 510 mg/kg for decaBDE, 1420 mg/kg for TBBPA (as an additive), 17 mg/kg for HBCD, 5500 mg/kg for bromine, and 1700 mg/kg for antimony. In comparison to data that have been calculated by SFA for Switzerland from literature for the 1990s, these measured concentrations in small size WEEE were 7 times higher for pentaBDE, unexpectedly about 50% lower for decaBDE, and agreed fairly well for TBBPA (as an additive) and octaBDE. Roughly 60% of the total bromine input determined by SFA based on X-ray fluorescence analysis of the output materials of the recycling plant cannot be assigned to the selected BFRs. This is an indication for the presence of other brominated substances as substitutes for PBDEs in electrical and electronic equipment. The presence of BFRs, in particular PBDEs in the low grams per kilogram concentration range, in the fine dust fraction recovered in the off-gas purification system of the recycling plant reveals a high potential for BFR emissions from WEEE management and point out the importance for environmentally sound recycling and disposal technologies for BFR-containing residues.

Summary Background Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non‐alcoholic fatty liver disease (NAFLD). In contrast to cirrhosis, advanced, non‐cirrhotic NAFLD is difficult to identify and data from Germany are lacking. Aim To identify clinical factors associated with advanced, non‐cirrhotic fibrosis. Methods Patients were recruited in the prospectively enrolling European NAFLD Registry. Clinical characteristics and the performance of non‐invasive surrogate scores compared with vibration‐controlled transient elastography are reported. Results Two hundred and sixty‐one patients with non‐cirrhotic NAFLD on liver biopsy (mean age 51 years, equal sex distribution) were included. The prevalence of stage 3 fibrosis on liver biopsy was 15.7%. These patients were significantly older (57 vs 50 years, P < 0.01), had a higher body mass index (32.3 vs 30.5, P < 0.05), and more frequent arterial hypertension (78% vs 50%, P = 0.001) and type 2 diabetes (61% vs 24.1%, P < 0.001). On multivariate logistic regression, diabetes (OR = 4.68, 95% CI 2.17‐10.10) and hypertension (OR = 2.91, 95% CI 1.12‐7.18) were independent predictors of advanced fibrosis. Comedication included metformin in 50% and insulin in 33% of patients with diabetes. Despite the presence of cardiovascular risk factors, the use of statins was low. Liver stiffness measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72‐0.91). The performance of NAFLD fibrosis score, Fibrosis‐4, and AST to platelet ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively. Conclusions The prevalence of metabolic comorbidities in a German population with non‐cirrhotic biopsy‐proven NAFLD is high. While the examined scores exhibit an acceptable specificity, liver stiffness measurement appeared to be superior to blood‐based non‐invasive surrogate scores in ruling out advanced fibrosis.

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Summary Background Lifestyle modifications remain the cornerstone of treatment in non‐alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes. Aims To evaluate the effects of a short, web‐based, individualised exercise program on non‐invasive markers of hepatic steatosis, inflammation and fibrosis. Methods Patients with histologically confirmed NAFLD underwent an 8‐week, web‐based, individualised exercise program that contained bidirectional feedback. Results Forty‐four patients entered the study and 41 completed the assigned training goal (93.2%). In the completer population, 8 weeks of individualised exercise increased the VO2peak by 12.2% compared to baseline (P < .001). ALT and AST decreased by 14.3% (P = .002) and 18.2% (P < .001) and remained at this level until follow‐up 12 weeks after the intervention. Markers of inflammation including hsCRP, ferritin, and M30 decreased. In parallel, gut microbiota exhibited increased metagenomic richness (P < .05) and at the taxonomic levels Bacteroidetes and Euryarchaeota increased whereas Actinobacteria phylum decreased. Surrogate scores of steatosis and fibrosis including the fatty liver index (FLI), FiB‐4, APRI and transient elastography showed significant reductions. In parallel, a marker of procollagen‐3 turnover (PRO‐C3) decreased while C4M2, reflecting type IV collagen, degradation increased suggesting beneficial hepatic fibrosis remodelling from exercise. Also, an enhancement in health‐related quality of life was reported. Conclusion The current study underlines the plausibility and potential of an 8 week individualised web‐based exercise program in NAFLD. Clinical trial number: NCT02526732

Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice.

Nonalcoholic fatty liver disease (NAFLD), depression, and anxiety disorders are frequent diseases, and data on mutual influence are inconsistent. The aim of this study was to explore the incidence of depression and anxiety in a large primary care cohort in Germany and to study the impact of NAFLD over a 10‐year time frame. Patients with NAFLD diagnosed between 2010 and 2015 were matched to a cohort without NAFLD controlling for age, sex, physician, index year, and Charlson comorbidity index. The primary outcome of the study was the incidence of depression, anxiety, and first prescription of antidepressant drugs. We compared 19,871 patients with NAFLD to 19,871 matched controls. Within 10 years of the index date, 21.2% of patients with NAFLD and 18.2% of controls were diagnosed with depression (P < 0.001). On regression analysis, the hazard ratio (HR) for incidence of depression was 1.21 (P < 0.001). This association was similar for the endpoint of the first prescription of antidepressant drugs (HR, 1.21; P < 0.001). Anxiety disorders were diagnosed in 7.9% of patients with NAFLD and 6.5% of controls during the observation time (P = 0.003). The HR for incidence of anxiety was 1.23 (P < 0.001). This association remained significant in women (P < 0.001), while there was only a trend in men (HR, 1.15; 95% confidence interval, 0.99‐1.34; P < 0.067). The risk of developing anxiety disorders was higher in younger patients. Conclusion: NAFLD constitutes an independent risk factor for emerging depression and anxiety even after controlling for confounding comorbidities.