Background & Aims The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aim to examine the differences between elderly and non-elderly patients with NAFLD, and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. Methods This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based upon availability of the centrally reviewed liver histology data within one year of enrollment, resulting in 61 elderly (aged ≥ 65 years) and 735 non-elderly (18–64 years) participants. Main outcomes were presence of NASH and advanced fibrosis. Results Compared to non-elderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 74%, P =0.02), and advanced fibrosis (25% versus 44%, P=0.002), respectively. Compared to non-elderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P=0.03), as well as other features of severe liver disease including presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤0.05 for each). In multivariable-adjusted logistic regression analyses, independent determinants of NASH in elderly patients included higher AST (odd ratio (OR)= 1.12, P=0.007) and lower platelets (OR= 0.98, P=0.02); and independent determinants of advanced fibrosis included higher AST (OR=1.10, P=0.002), lower ALT value (OR= 0.91, P=0.001) and an increased odds of having low HDL (OR=12.62, P=0.004). Conclusions Elderly patients are more likely to have NASH and advanced fibrosis than non-elderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis.

Background & Aims No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. Methods We performed a double-masked trial of 169 children with NAFLD Activity Scores ≥ 4 at 10 centers. From June 2012 to January 2014, the patients were randomly assigned to receive CBDR or placebo twice daily (300 mg for ≤65 kg, 375 mg for >65–80 kg, 450 mg for >80 kg) for 52 weeks. The primary outcome from the intention to treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in NAFLD Activity Score ≥ 2 points without worsening fibrosis; patients without biopsies from week 52 (17 in the CBDR group and 6 in the placebo group) were considered non-responders. We calculated relative risks (RR) of improvement using stratified Cochran-Mantel-Haenszel analysis. Results There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% CI, 0.8–2.1; P=.34). However, children receiving CBDR had significant changes in pre-specified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction of 53±88 U/L vs a reduction of 8±77 U/L in the placebo group; P=.02) and aspartate aminotransferase (reduction of 31±52 vs a reduction of 4±36 U/L in the placebo group; P=.008), and a larger proportion had reduced lobular inflammation (in 36% of patients in the CBDR group vs placebo 21% of patients in the placebo group; RR, 1.8; 95% CI, 1.1–2.9; P=.03). In a post-hoc analyses, of children ≤65 kg, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3–12.3; P=.005). Conclusions In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR did, however, have significant reductions in serum levels of aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.

Osteoarthritis (OA), a leading cause of disability and pain, affects 32.5 million Americans, producing tremendous economic burden. Although some findings suggest that racial/ethnic minorities experience increased OA pain severity, other studies have shown conflicting results. This metaanalysis examined differences in clinical pain severity between African Americans (AAs) and non-Hispanic whites with OA. Articles were initially identified between October 1 and 5, 2016, and updated May 30, 2018, using PubMed, Web of Science, PsycINFO, and the Cochrane Library Database. Eligibility included English-language peer-reviewed articles comparing clinical pain severity in adult black/ AA and non-Hispanic white/Caucasian patients with OA. Nonduplicate article abstracts (N = 1,194) were screened by 4 reviewers, 224 articles underwent full-text review, and 61 articles reported effect sizes of pain severity stratified by race. Forest plots of the standard mean difference showed higher pain severity in AAs for studies using the Western Ontario and McMasters Universities Osteoarthritis Index (0.57; 95% confidence interval [CI], 0.54−0.61) and non-Western Ontario and McMasters Universities Osteoarthritis Index studies (0.35, 95% CI, 0.23−0.47). AAs also showed higher self-reported disability (0.38, 95% CI, 0.22−0.54) and poorer performance testing (-0.58, 95% CI,-0.72 to-0.44). Clinical pain severity and disability in OA is higher among AAs and future studies should explore the reasons for these differences to improve pain management. Perspective: This meta-analysis shows that differences exist in clinical pain severity, functional limitations, and poor performance between AAs and non-Hispanic whites with OA. This research may lead to a better understanding of racial/ethnic differences in OA-related pain.

Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. We collected data from 3 large US studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. We found that pre-menopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than post-menopausal women (P<.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in pre-menopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in post-menopausal women (P<.05). We conclude that being a pre-menopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

BACKGROUND & AIMS: Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship of opioid use to gastroparesis manifestations are undefined. We characterized associations of use of potent vs weaker opioids and presentations of diabetic and idiopathic gastroparesis. METHODS: We collected data on symptoms, gastric emptying, quality of life, and health care resource use from 583 patients with gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Consortium, from January 2007 through November 2016. Patients completed medical questionnaires that included questions about opioid use. The opioid(s) were categorized for potency relative to oral morphine.