Nutrient Intake Differs Among Persons With Celiac Disease and Gluten-Related Disorders in the United States

Persons with celiac disease (CD) may develop nutritional deficiencies, while individuals following a gluten-free diet (GFD) may lack essential nutrients. We examined nutrient intake from diet and supplements among persons with CD and GFD in the cross-sectional National Health and Nutrition Examination Survey, 2009-2014. Among 15,610 participants 20 years and older, we identified CD based on positive serology for immunoglobulin A against tissue transglutaminase, health care provider diagnosis, and adherence to a GFD. People without CD avoiding gluten (PWAG) adhered to a GFD without a diagnosis of CD. Two 24-h recalls assessed nutrient intake from diet and supplements. Compared to participants without CD or PWAG, persons with diagnosed CD had lower intake of total energy, carbohydrates, fat, and saturated and monounsaturated fatty acids. In contrast, persons with undiagnosed CD and positive serology had higher intake of those nutrients, sugar, and protein. Total carbohydrate and sugar intake was lower among PWAG. Persons with diagnosed CD had higher vitamin A and E intake, while those with undiagnosed CD had increased intake of calcium, phosphorus, magnesium, iron, zinc, copper, sodium, potassium, vitamin A, alpha-carotene, folic acid, and choline. Higher micronutrient intake with undiagnosed CD was observed more at high latitudes. PWAG had higher beta-carotene and lutein/zeaxanthin and lower folic acid intake. In the U.S. population over a 6-year period, total energy and macronutrient intake was decreased among persons with diagnosed CD, while intake of total energy, macronutrients, and multiple micronutrients was increased among persons with undiagnosed CD. Nutriomics studies of multiple analytes measured simultaneously across affected persons and populations are needed to inform screening for malabsorption and treatment strategies

Histologic Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels.

Objectives: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26–50 U/L boys, 23–44 U/L girls), or elevated (> 50 boys, > 44 girls) serum alanine aminotransferase (ALT) levels. Study design: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) enrolls children 5–18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy within 180 days of ALT, and compared them with 392 children with elevated ALT. Results: Of 91 children, 17 (19%) had normal and 74 (81%) had mildly elevated ALT levels. Overall, 45% of biopsies had ≥ 33% steatosis, lobular inflammation grade was ≥ 2 in 22%, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, and 8% had definite NASH, 34% had NAFLD activity score (NAS) ≥ 4. Overall, 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in mildly elevated vs normal, with no difference in ballooning, inflammation, or NAS ≥ 4. Fibrosis stage 3/4 was seen in none of the children with normal ALT, and in 9% of the mildly elevated and 15% of the elevated. Conclusions: Liver biopsies of children with NAFLD with normal or mildly elevated ALT levels show significant histologic abnormalities, including advanced fibrosis in children with mildly elevated ALT. ALT thus may underestimate liver injury in NAFLD. Appropriate ALT cut-off levels can help identify children at risk for more severe disease

Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Background Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. Methods We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes 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 primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate 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 pioglitazone, as compared with placebo (P Conclusions Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT00063622.

FDA Censoring of Manufacturers\u27 Postmarketing Commitments in HIV/AIDS Drug Approval Letters

Context: Changing evidentiary standards and partial shift of the investigational phase of drug approval process to the postmarketing phase. Objective: To determine the availability of information for independent researchers needed to examine accelerated drug approvals to determine how they differ from traditional drug approvals in the HIV/AIDS domain. Design: Identification of all approved HIV/AIDS and AIDS-related conditions drugs between 1987 and 1999. Follow-up of postmarketing study requirements in the approval letters addressed to the manufacturers. Setting: Accelerated approval has been expanded to other disease conditions in the past decade. Intervention: Request of approval letters from the U.S. Food and Drug Administration for 76 regulatory actions including expanded access and accelerated and traditional approvals for 42 drugs under the Freedom of Information Act (FOIA) between September 1998 and October 1999. Main Outcome Measure(s): Obtainability of approval letters and uncensored postmarketing study requirements. Results: Fifty-five approval letters were received. Postmarketing study commitments of manufacturers were censored in 25 letters received. We were unable to obtain uncensored copies of those approval letters as of May 2000. Censoring was associated with whether (1) the Prescription Drug User Fee Act of 1992 was applicable to the drug (odds ratio (OR) = 5.7,95% confidence interval (CI) = 1.4-23.7) and (2) the new drug application was for a new molecular entity or new drug formulation (OR = 4.2, 95% CI = 1.3-13.6). Conclusions: Continued secrecy may stifle independent research and hinder health care providers and patients in making informed decisions

FDA Censoring of Manufacturers\u27 Postmarketing Commitments in HIV/AIDS Drug Approval Letters

Context: Changing evidentiary standards and partial shift of the investigational phase of drug approval process to the postmarketing phase. Objective: To determine the availability of information for independent researchers needed to examine accelerated drug approvals to determine how they differ from traditional drug approvals in the HIV/AIDS domain. Design: Identification of all approved HIV/AIDS and AIDS-related conditions drugs between 1987 and 1999. Follow-up of postmarketing study requirements in the approval letters addressed to the manufacturers. Setting: Accelerated approval has been expanded to other disease conditions in the past decade. Intervention: Request of approval letters from the U.S. Food and Drug Administration for 76 regulatory actions including expanded access and accelerated and traditional approvals for 42 drugs under the Freedom of Information Act (FOIA) between September 1998 and October 1999. Main Outcome Measure(s): Obtainability of approval letters and uncensored postmarketing study requirements. Results: Fifty-five approval letters were received. Postmarketing study commitments of manufacturers were censored in 25 letters received. We were unable to obtain uncensored copies of those approval letters as of May 2000. Censoring was associated with whether (1) the Prescription Drug User Fee Act of 1992 was applicable to the drug (odds ratio (OR) = 5.7,95% confidence interval (CI) = 1.4-23.7) and (2) the new drug application was for a new molecular entity or new drug formulation (OR = 4.2, 95% CI = 1.3-13.6). Conclusions: Continued secrecy may stifle independent research and hinder health care providers and patients in making informed decisions

Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non-diabetic patients

Background: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. Methods: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. Results: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. Conclusion: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype