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Background: The features and risk analysis of non-alcoholic fatty liver disease (NAFLD) in a community-based setting remain elusive. The predictors between obese and lean subjects need further clarification. We aimed to assess the characteristics of NAFLD during a community screening. The associated metabolic abnormalities and cardiovascular risk assessment were also analyzed. Methods: A total of 2483 subjects receiving multi-purpose health screening at 10 primary care centers were recruited. They received clinical assessment, including demographic data, laboratory examination, and abdominal sonography. Results: The prevalence of NAFLD and metabolic syndrome were 44.5%, and 15.8%, respectively. Among those NAFLD subjects, 1212 (48.8%) subjects were obese (BMI≥ 24 kg/m2). There was an increasing trend of NAFLD according to age, ranging from 25.8% of those aged 27 kg/m2 (P for trend< 0.0001). Conclusion: IR is predictive of NAFLD irrespective of BMI. The cardiovascular risk may exist in lean NAFLD subjects. Keywords: Non-alcoholic fatty liver disease, Metabolic syndrome, Insulin resistance, Risk assessment, Community screening

Background/purpose: The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and efficacy of a protease inhibitor, boceprevir, in combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually-infected patients refractory to prior peginterferon/ribavirin. Methods: Twelve peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned to receive boceprevir 800 mg, twice a day, plus peginterferon-α 2b 1.5 μg/kg/week and ribavirin 800-1400 mg/day for 36 or 48 weeks. The primary endpoint was HCV sustained virological response (SVR, HCV RNA undetectable 24 weeks after end-of-treatment). Results: Five patients terminated treatment early due to adverse events (one at week 4, one at week 46), virological failures (one non-response and one breakthrough), and patient request (n = 1). Eight patients achieved HCV SVR (66.7% in full-analysis set and 72.7% in modified intention-to-treat population). The HCV SVR rate was 71.4% (5/7) in prior relapsers, 60.0% (3/5) in prior null responder; 75% in non-cirrhotic and 50% in cirrhotic patients. All four patients of prior non-cirrhotic relapsers received 36-week regimen and achieved HCV SVR. There was no HBV-related hepatic flare. All patients experienced at least one adverse event. Two had serious adverse events. Conclusion: Boceprevir plus peginterferon/ribavirin is effective in the treatment of HCV-1/HBV dually infected patients' refractory to prior peginterferon/ribavirin combination therapy. Keywords: Boceprevir, HBV, HCV, Taiwan

Chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely unclarified. Oxidative stress, in particular, DNA lesions associated with oxidative damage, plays a major role in carcinogenesis, and is strongly linked to the development of many cancers, including HCC. However, in identifying hepatocytes with HCV viral RNA, estimates of the median proportion of HCV-infected hepatocytes have been found as high as 40% in patients with chronic HCV infection. In order to explore the gene alternation and association between different viral loads of HCV-infected cells, we established a method to dissect high and low viral load cells and examined the expression of DNA damage-related genes using a quantitative polymerase chain reaction array. We found distinct expression patterns of DNA damage-related genes between high and low viral load cells. This study provides a new method for future study on virus-associated gene expression research.

Whether silver nanoparticles (AgNPs) persist or release silver ions (Ag + ) when discharged into a natural environment has remained an unresolved issue. In this study, we employed a low-cost stereolithographic three-dimensional printing (3DP) technology to fabricate the angle-defined knotted reactors (KRs) to construct a simple differentiation scheme for quantitative assessment of Ag + ions and AgNPs in municipal wastewater samples. We chose xanthan/phosphate-buffered saline as a dispersion medium for in situ stabilization of the two silver species, while also facilitating their extraction from complicated wastewater matrices. After method optimization, we measured extraction efficiencies of 54.5 and 32.3% for retaining Ag + ions and AgNPs, respectively, in the printed KR (768-turn), with detection limits (DLs) of 0.86 and 0.52 ng L −1 when determining Ag + ions and AgNPs, respectively (sample run at pH 11 without a rinse solution), and 0.86 ng L −1 when determining Ag + ions alone (sample run at pH 12 with a 1.5-mL rinse solution). The proposed scheme is tolerant of the wastewater matrix and provides more reliable differentiation between Ag + /AgNPs than does a conventional filtration method. The concept and applicability of adopting 3DP technology to renew traditional KR devices were evidently proven by means of these significantly improved analytical performance. Our analytical data suggested that the concentrations of Ag + ions and AgNPs in the tested industrial wastewater sample were both higher than those in domestic wastewater, implying that industrial activity might be a main source of environmental silver species, rather than domestic discharge from AgNP-containing products.

Background & Aims Genetic variants of patatin-like phospholipase domain-containing 3 ( PNPLA3 ) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis. Methods The PNPLA3 genetic polymorphism at rs738409 was verified in 1077 biopsy-proven CHC patients. Other clinical variables, including diabetes status, were analysed for factors associated with bridging fibrosis. Results Patients with advanced liver fibrosis had higher proportions of the GG genotype (14.5% vs. 10.4%, p= 0.06 in recessive model) and GG/GC genotype carriage (64.0% vs. 56.8%, p= 0.03 in dominant model). Stepwise logistic regression analysis revealed that factors predictive of advanced liver fibrosis included age (odds ratio [OR]: 1.02, 95% confidence intervals [CI]: 1.008–1.037, p= 0.002), diabetes (OR: 1.81, CI: 1.236–2.653, p= 0.002), α-fetoprotein (OR: 1.006, CI: 1.001–1.01, p= 0.01), platelet counts (OR: 1.009, CI: 1.006–1.012, p 0.001), and PNPLA3 rs738409 CG/GG genotype (OR: 1.34, CI: 1.006–1.785, p= 0.046). When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients. The PNPLA3 gene was the most important predictive factor of bridging fibrosis in diabetic patients, using the recessive model (OR: 4.53, CI: 1.356–15.106, p= 0.014) or the dominant model (OR: 2.20, CI: 1.026–4.734, p= 0.04). Compared to non-diabetic patients, patients with the diabetes/GG genotype were more likely to have advanced liver fibrosis (OR: 8.79, CI: 2.889–26.719, p 0.001), followed by those with diabetes/non-GG genotype (OR: 1.55, CI: 1.048–2.286, p= 0.03). Conclusions The effect of PNPLA3 genetic variants in HCV-related advanced liver fibrosis was enhanced in diabetic patients. The strong genetic–environmental interaction contributed to the high risk of advanced liver disease in CHC patients.

Background & Aims: Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods: A total of 642 patients with an SVR after peginterferon/ ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results: Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI 2.32–10.71, p

Therapeutic angiogenesis is essential for rescuing necrotic tissues in cases of ischemic disease. The exogenous hydrogen sulfide (H2S) donor, diallyl trisulfide (DATS), has been investigated as a therapeutic agent that promotes angiogenesis. However, the short half-life of generated H2S limits its therapeutic efficacy. In an attempt to overcome this difficulty, a poly(D,L-lactic-co-glycolic acid) microparticle system that contains DATS (DATS@MPs) is prepared as an in situ depot for the controlled release of H2S, providing slow release and long-term effectiveness. The results of in vitro investigations indicate that the slow-released DATS from the DATS@MPs depot yields a longer intracellular production of H2S than that from a free DATS depot. The intracellular generation of H2S favors the translocation of the transcription factor, Nrf2, from the cytosol to nuclei, potentially upregulating the gene expressions of antioxidant enzymes, ultimately increasing cellular resistance to oxidative stress. Intramuscular injection of the slow-releasing H2S donor depot DATS@MPs in an ischemic limb that is experimentally generated in a mouse model promotes therapeutic angiogenesis and protects cells from apoptosis and tissues from necrosis, ultimately salvaging the limb. These analytical results reveal that DATS@MPs is potentially useful in H2S-based therapy for treating ischemic diseases.