The Effects of Vitamin E, Silymarin and Carnitine on the Metabolic Abnormalities Associated with Nonalcoholic Liver Disease.

The obesity epidemic has resulted in an increase in the incidence of metabolic syndrome, and liver disease. Studies indicate that antioxidant supplementation may improve abnormal liver chemistries, glucose control, and hyperlipidemia, in patients with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to determine the normalization of abnormalities in hepatic function testing in patients with NAFLD when treated with vitamin E 200 IU, Silymarin 750 mg, and l-carnitine 1 gram (VSC) for 18 weeks in comparison to a placebo-controlled group. Secondary objectives were to evaluate changes in blood glucose level, insulin, total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), C-reactive protein (CRP), hemoglobin A1C (HgA1c), and homeostatic models assessment (HOMA) in patients treated with VSC vs placebo. Findings showed that VSC caused a significant reduction in serum glucose, insulin, and HOMA levels. While there were downtrends in the other measured values these were not statistically significant. In this 18-week study, the ability of this supplement in reducing markers of liver inflammation, glucose, insulin, and triglycerides indicate that this supplement could play an important role in the treatment of nonalcoholic fatty liver disease, diabetes, and the metabolic syndrome.

Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial.

BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.

Propofol compared with combination propofol or midazolam/fentanyl for endoscopy in a community setting.

This retrospective cohort study evaluated procedural efficiency and patient satisfaction in patients who had received propofol, midazolam/fentanyl/propofol (MFP), or midazolam/fentanyl, as sedation for either esophagogastroduodenoscopy or colonoscopy. Questionnaires about procedural times and patient satisfaction were administered. Use of propofol for colonoscopy resulted in shorter time (minutes) from induction to start of procedure (mean +/- standard deviation: propofol, 1.3 +/- 0.57; MFP, 3.2 +/- 2.2; midazolam/fentanyl, 3.8 +/- 2.7; P < .04) and shorter procedure time (propofol, 13 +/- 0.36; MFP, 15 +/- 0.004; midazolam/fentanyl, 75 +/- 0.005 minutes; P < .05). Recovery time was less for patients receiving propofol for their colonoscopy compared with the other groups (propofol, 9 +/- 8; MFP, 15 +/- 9; midazolam/ fentanyl, 18 +/- 117 minutes; P < .05). Patients undergoing esophagogastroduodenoscopy who received propofol had a shorter recovery time (9 +/- 7 minutes vs MFP, 14 +/- 9 minutes, and midazolam/fentanyl, 19 +/- 11 minutes; P < .05). Patients receiving propofol felt less discomfort and need for adjustment in the sedation, and remembered less of the procedure compared with the MFP group. Propofol resulted in less time in the endoscopy unit, quicker recovery and discharge, and greater patient satisfaction than did balanced or conscious sedation.

Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective.

BACKGROUND: There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. CASE: The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. CONCLUSIONS: Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm.

The ethanol metabolite, linolenic acid ethyl ester, stimulates mitogen-activated protein kinase and cyclin signaling in hepatic stellate cells.

Chronic ethanol consumption can result in hepatic fibrosis and cirrhosis. In addition to oxidative metabolism, ethanol can be metabolized by esterification with fatty acids to form fatty acid ethyl esters (FAEE) such as linolenic acid ethyl ester (LAEE). We have previously demonstrated that LAEE has promitogeinc and activating effects on hepatic stellate cells (HSC), but the mechanisms of these actions are not known. Intracellular signaling through MAP kinase pathways, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) can influence the activity of the transcription factor AP-1, while cell-cycle regulatory proteins such as cyclin E and cyclin-dependent kinase (CDK), play an important role in cell proliferation. In this study, we demonstrate that treatment of HSC with LAEE increases cyclin E expression and cyclin E/CDK2 activity, which may underlie the promitogenic effects of this compound. In addition, LAEE increases ERK and JNK activity, and these pathways play an important role in the activation of AP-1-dependent gene expression by LAEE. The stimulation of intracellular signaling pathways in HSC by this well-characterized ethanol metabolite may contribute to ethanol-induced hepatic fibrogenesis.