on behalf of the WELCOME Study InvestigatorsThere is no licensed treatment for nonalcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes, and cardiovascular disease. We tested whether 15-18 months of treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA; Omacor/Lovaza, 4 g/day) decreased liver fat and improved two histologically validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomized in a double-blind, placebo-controlled trial (DHA1EPA, n 5 51; placebo, n 5 52). We quantified liver fat percentage by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA; placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of (1) DHA1EPA treatment (intention-to-treat analyses) and (2) erythrocyte DHA and EPA enrichment (secondary analysis). Median (interquartile range) baseline and end-of-study liver fat percentage were 21.7 (19.3) and 19.7 (18.0) (placebo) and 23.0 (36.2) and 16.3 (22.0) (DHA1EPA). In the fully adjusted regression model, there was a trend toward improvement in liver fat percentage with DHA1EPA treatment (b 5 23.64; 95% confidence interval [CI]: 28.0, 0.8; P 5 0.1), but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat percentage (for each 1% enrichment: b 5 21.70; 95% CI: 22.9, 20.5; P 5 0.007). No improvement in fibrosis scores occurred. Conclusion: Erythrocyte DHA enrichment with DHA1EPA treatment is linearly associated with decreased liver fat percentage. Substantial decreases in liver fat percentage can be achieved with high-percentage erythrocyte DHA enrichment in NAFLD. (HEPATOLOGY 2014;60:1211-1221

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Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardiorespiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1-and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome. Key words: Clinical liver transplantation, cystic fibrosisAbbreviations: ATG, anti-thymocyte globulin; BMI, body mass index; CF, cystic fibrosis; CNI, calcineurin inhibitor; FEV 1 , forced expiratory volume in 1 second; HIV, human immunodeficiency virus; IVC, inferior vena cava; MELD, model for end-stage liver disease; TIPS, transjugular intrahepatic porto-systemic shunt; UK, United Kingdom.

Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.

Staphylococcus aureus is an uncommon pathogen in bronchiectasis not caused by cystic fibrosis (CF). The object of this study was to identify characteristics that cause patients to be prone to infection with S. aureus.The study population consisted of patients with bronchiectasis attending the authors' unit, excluding those with a diagnosis of overt CF. All patients had a high resolution computer tomographic scan (HRCT) of the thorax which demonstrated bronchiectasis. Cases that were currently chronically infected with S. aureus (isolated consecutively on more than two occasions >3 months apart) were identified (n=12) and compared with 74 control patients who had not been chronically infected with S. aureus. Patients were carefully evaluated to determine the aetiology of their disease. Odds ratios (OR) and 95% confidence intervals (CI) as measures of the association between disease characteristics and chronic infection with S. aureus were calculated.The results for patients chronically infected by S. aureus demonstrated significant associations with allergic bronchopulmonary aspergillosis (ABPA; OR=8.8, 95% CI 1.8±41.9), atypical variants of CF (OR=12.0, 95% CI 1.8±81.7) or equivocal sweat sodium values (OR=4.0, 95% CI 1.0±15.3). The associations persisted when the analysis was based on cases (n=28) in whom S. aureus had ever been isolated from sputum. In the latter analysis there was also a significant association with predominant upper zone disease on HRCT.These results suggest that patients with bronchiectasis in whom S. aureus is isolated from sputum should be carefully evaluated to exclude allergic bronchopulmonary aspergillosis or atypical cystic fibrosis. Eur Respir J 1999; 14: 1340±1344. Staphylococcus aureus is a gram positive coccus which is only occasionally cultured from the sputum of patients with bronchiectasis [1], whereas in patients with cystic fibrosis (CF) it is almost always the initial bacterial infection [2±4]. In CF S. aureus infection may stimulate an inflammatory response that causes lung damage and facilitates subsequent chronic infection with Pseudomonas aeruginosa [2±4]. Once chronic infection with P. aeruginosa has occurred S. aureus is less frequently cultured and it has been suggested that this is due to anti-staphylococcal factors produced by P. aeruginosa [5]. Several reports of sputum microbiology and bronchoscopic sampling suggest that S. aureus occurs in~4±10% of patients with non-CF bronchiectasis [6±8]. The reason for this difference in the type of bacterial infective organisms is unclear. The object of the present study was to identify common characteristics of a group of patients with non-CF bronchiectasis who were chronically infected with S. aureus. Methods Study definitionsChronic infection with S. aureus was defined as patients who were infected with S. aureus during the study period and the bacterium had been isolated from consecutive sputum samples taken on more than two occasions >3 months apart. Intermittent infection with S. aureus was defined when the ba...

Telbivudine is a new antiviral agent joining the armamentarium against HBV. It is superior to lamivudine in terms of therapeutic response and resistance profile. However, concerns about resistance with long-term use, along with inferior cost-effective analyses, have relegated telbivudine to a second-line agent in the management of chronic HBV infection.

More than 180 million people worldwide have chronic hepatitis C (CHC) virus infection, a major cause of liver cirrhosis and its life-threatening complications including liver failure, portal hypertension, and hepatocellular carcinoma. With the current standard of care of pegylated interferon-alpha and ribavirin (PEG-IFN-alpha/RBV), the chances of sustained viral clearance or "cure" are only 40%-50% for genotype 1 infection, which is the most common genotype in western populations. Consequently, there has been a drive to develop new agents specifically targeting essential components of the viral life cycle, such as the hepatitis C virus (HCV) NS3/4A serine protease. Perhaps the most advanced HCV protease inhibitor in clinical development is telaprevir, which has been shown to improve treatment outcomes when combined with PEG-IFN-alpha/RBV in genotype 1 infection, and is currently undergoing phase 3 study. In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC.

Background: Outside South-East Asia, most cases of cholangiocarcinoma (CCA) have an obscure etiology. There is often diagnostic uncertainty. Metabolomics using ultraperformance liquid chromatography mass spectrometry (UPLC-MS) offers the portent to distinguish disease-specific metabolic signatures. We aimed to define such a urinary metabolic signature in a patient cohort with sporadic CCA and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma (HCC), metastatic secondary liver cancer, pancreatic cancer and ovarian cancer (OCA). Methods: Spot urine specimens were obtained from 211 subjects in seven participating centers across the UK. Samples were collected from healthy controls and from patients with benign hepatic disease (gallstone, biliary strictures, sphincter of Oddi dysfunction and viral hepatitis) and patients with malignant conditions (HCC, pancreatic cancer, OCA and metastatic cancer in the liver). The spectral metabolite profiles were generated using a UPLC-MS detector and data were analyzed using multivariate and univariate statistical analyses. Results: The greatest class differences were seen between the metabolic profiles of disease-free controls compared to individuals with CCA with altered acylcarnitine, bile acid and purine levels. Individuals with benign strictures showed comparable urine profiles to patients with malignant bile duct lesions. The metabolic signatures of patients with bile duct tumors were distinguishable from patients with hepatocellular and ovarian tumors, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases. Conclusion: CCA causes subtle but detectable changes in the urine metabolic profiles. The findings point toward potential applications of metabonomics in early tumor detection. However, it is key to utilize both global and targeted metabonomics in a larger cohort for in-depth characterization of the urine metabolome in hepato-pancreato-biliary disease.