Search

BACKGROUND: Chronic inflammation in IBD is postulated to drive NAFLD progression from steatosis to fibrosis. AIMS: To study the histopathological spectrum of NAFLD in Crohn disease (CD) and Ulcerative colitis (UC). METHODS: Patients with biopsy proven NAFLD at a quaternary center from 2008 to 2018 were included in this retrospective analysis. Inflammatory bowel disease (IBD) diagnosed either clinically and/or endoscopically at the time of liver biopsy. Multivariable regression and propensity score (PS) weighted analysis were conducted. Statistical analysis were performed using SAS statistical software. RESULTS: Among 1009 patients with NAFLD a diagnosis of IBD was identified in 50 cases (34 CD and 16 UC). On multivariable analysis; CD was independently associated with significantly higher odds of advanced fibrosis (AF) on liver biopsy (adjusted OR = 4.09, 95% CI = 1.40–11.94) compared to NAFLD patients without IBD. Similar results were obtained with both the overlap PS weighted model (OR = 3.17, 95% CI = 1.55–6.49) and the PS matched model (OR = 3.49, 95% CI = 1.50–8.13). CONCLUSION: In a large cohort of patients with histologically well characterized NAFLD, AF was more common in CD patients than NAFLD patients without IBD. These findings must be confirmed in a larger cohort, but suggest CD patients with NAFLD could be at greater risk for liver fibrosis.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P0.001) compared with patients without cannabis abuse.Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.

Lifestyle changes and metabolic syndrome management are the best interventions for NAFLD. Less clear is which agents to use for liver-directed pharmacotherapy.

Background Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrho­ sis. Currently, there is no established treatment for this disease. Methods We randomly assigned 247 adults with nonalcoholic steatohepatitis and without dia­ betes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The pri­ mary outcome was an improvement in histologic features of nonalcoholic steato­ hepatitis, as assessed with the use of a composite of standardized scores for steato­ sis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indi­ cate statistical significance. Results Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0. 001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P = 0. 04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pio­ glitazone, as compared with placebo (P

Summary Background The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis. Methods We did a multicentre, double-blind, placebo-controlled, parallel group, randomised clinical trial at medical centres in the USA in patients with non-cirrhotic, non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally (25 mg daily) or placebo for 72 weeks. Patients were randomly assigned 1:1 using a computer-generated, centrally administered procedure, stratified by clinical centre and diabetes status. The primary outcome measure was improvement in centrally scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment. A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment (72 weeks) biopsies supported the decision to continue the trial (relative change in alanine aminotransferase −24%, 95% CI −45 to −3). A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid (p=0·0024) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients, but to continue the trial to obtain the 24-week post-treatment measures. Analyses were done by intention-to-treat. This trial was registered with ClinicalTrials.gov, number NCT01265498. Findings Between March 16, 2011, and Dec 3, 2012, 141 patients were randomly assigned to receive obeticholic acid and 142 to placebo. 50 (45%) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 (21%) of 109 such patients in the placebo group (relative risk 2·2, 95% CI 1·4 to 3·3; p=0·0002). 33 (23%) of 141 patients in the obeticholic acid developed pruritus compared with nine (6%) of 142 in the placebo group. Interpretation Obeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification. Funding National Institute of Diabetes and Digestive and Kidney Diseases, Intercept Pharmaceuticals.

Over the last five years 175 students at the University of Ulster have done a final year sociology module on placement. The key to placement as a setting for sociologists is that a diversity of knowledge from theoretical sociology, classic writers, case studies and textbooks are all potentially relevant to it. It connects theory and practice and provides organisational experiences from which students can develop comparative and theoretical insights applied to their possible roles in society. It also provides practical and critical skills suited to future employment. Students see their academic and personal reputation directly at stake during placement and in most cases are eager to find their own places in order to work well in their local environment.

To The Editor: We read with great interest the article by Hong et al. published in August 2013 in the online version of Hepatology. Hong et al. report an increased risk of nonalcoholic fatty liver disease in patients with lower muscle mass. Here we take the chance to share the results of a study we conducted to investigate the presence of sarcopenia in patients with Nonalcoholic steatohepatitis "NASH" and NASH-related cirrhosis. NASH is an aggressive form of nonalcoholic fatty liver disease. It is widely accepted now that NASH is associated with insulin resistance(1), and can progress to cirrhosis in 21–28% of patients(2). Pro-inflammatory cytokines and insulin resistance result in muscle catabolism leading to muscle wasting "sarcopenia" in obese patients(3). In addition, sarcopenia is being more frequently described and addressed in cirrhotic patients(4). In our study, we divided the subjects into three groups, each one included 25 individuals; control group, NASH and NASH-cirrhosis groups. The diagnosis of NASH was proven by liver biopsy. To assess the presence of sarcopenia, we evaluated the muscle mass by measuring the cross-sectional area of the psoas and paraspinal muscles at the level of the midpoint of L4 vertebra on computed tomography (CT) scan (5). Total psoas and paraspinal muscles densities were also measured. Analysis of covariance was performed to assess differences in muscle area while adjusting for age and gender. Our results showed that patients with NASH and NASH-related cirrhosis were older and had higher body mass index than the control group. There was a stepwise significant decrease in total psoas area "TPA" from the control group to NASH group to cirrhosis group (29.3 ± 0.88 cm2, 24.8 ± 0.8 cm2, and 19.3 ± 0.93 cm2, respectively, p< 0.001). This difference remained significant after adjusting for age, gender and height(Figure). Similar findings were noted for the paraspinal muscle area. The density of the muscles as assessed by Hounsfield units was lower in patients with NASH or cirrhosis suggesting fatty infiltration (controls 36.9 ± 2.6 HU, NASH 31.2 ± 2.3, cirrhosis 18.5 ± 2.7). Figure Age and Gender Adjusted Means (95% Confidence Limits) for TPA/Height2 and Paraspinal Muscle Area/Height2 In conclusion, our data suggest that there is progressive muscle wasting in patients with NASH that precedes the development of cirrhosis and worsens with progression to cirrhosis.

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 microgram/kg/min. The infusions lasted for 2 hours and were flanked by both baseline and recovery periods. There was a significant effect of placebo on urinary sodium and chloride excretion rates but no effect on urine flow rate. In response to anaritide, the urine flow rate increased at 0.03, 0.06, 0.075, and 0.100 microgram/kg/min. The sodium and chloride excretion rates increased at all doses except the highest dose. There was no definite effect of anaritide on urinary potassium, calcium, and phosphate excretion rates. There was also no significant effect on creatinine clearance. The mean arterial pressure decreased in response to the 0.060, 0.075, and 0.100 microgram/kg/min doses. In addition, five of the patients receiving the highest dose (0.300 microgram/kg/min) had decreases in their systolic pressures to 90 mm Hg or less. In conclusion, anaritide is natriuretic and diuretic in patients with cirrhosis complicated by ascites and/or edema. Its effect, however, on arterial pressure may limit its therapeutic potential in this patient population.

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A "per protocol" analysis of healing rates showed a significant advantage for omeprazole (P less than 0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P less than 0.01) in the omeprazole group. "All-patients treated" analyses for healing and pain relief gave results similar to the respective "per protocol" analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (greater than 150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

This study had its inception some six years ago in a Master's Thesis, Plot Structure in Peele's Plays, which was presented to the Graduate Faculty of the University of Texas in August, 1925. In this thesis I studied the structure of Peele's The Arraignment of Paris, Edward I, The Old Wives Tale, David and Bethsabe, and of The Battle of Alcazar, and on the basis of the findings in these plays gave a brief and, I now think, unsatisfactory discussion of the structure and authorship of certain anonymous plays. Believing in the essential soundness of my original plan, I have rewritten the first five chapters of my earlier thesis into pages 20-63 and 267-279 of the present study. In undertaking a new discussion of the Peele canon, however, I have greatly enlarged my original design and have studied the characterization, use of sources, and style in the known plays of Peele, using the results obtained as the basis of a detailed investigation of several anonymous plays. My original thesis, therefore, has been little more than a point of departure for the study in hand