Activity

005), and to a lesser degree with HOMA-IR (ρ = 0.25; P = 0.051). The association of liver fat with LP-IR was limited to patients without diabetes (ρ = 0.60; P less then 0.0001), whereas no association was seen in those with diabetes. In a multivariate model, Adipo-IR, LP-IR, and diabetes were independently associated with liver fat and together explained 35% of the variability in liver fat. Conclusion LP-IR is a reasonable measure of IR in non-diabetic patients with NAFLD and is associated with hepatic fat content. Although adipose tissue is the major contributor to liver fat, the additional contribution of nonadipose tissues can be easily estimated using LP-IR.Resmetirom (MGL-3196), a selective thyroid hormone receptor-β agonist, was evaluated in a 36-week paired liver biopsy study (NCT02912260) in adults with biopsy-confirmed nonalcoholic steatohepatitis (NASH). MLN4924 ic50 The primary endpoint was relative liver fat reduction as assessed by MRI-proton density fat fraction (MRI-PDFF), and secondary endpoints included histopathology. Subsequently, a 36-week active treatment open-label extension (OLE) study was conducted in 31 consenting patients (including 14 former placebo patients) with persistently mild to markedly elevated liver enzymes at the end of the main study. In patients treated with resmetirom (80 or 100 mg orally per day), MRI-PDFF reduction at OLE week 36 was -11.1% (1.5%) mean reduction (standard error [SE]; P less then 0.0001) and -52.3% (4.4%) mean relative reduction, P less then 0.0001. Low-density lipoprotein (LDL) cholesterol (-26.1% [4.5%], P less then 0.0001), apolipoprotein B (-23.8% [3.0%], P less then 0.0001), and triglycerides (-19.6% [5.4%], P = 0.0012; -46.1 [14.5] mg/dL, P = 0.0031) were reduced from baseline. Markers of fibrosis were reduced, including liver stiffness assessed by transient elastography (-2.1 [0.8] mean kilopascals [SE], P = 0.015) and N-terminal type III collagen pro-peptide (PRO-C3) (-9.8 [2.3] ng/mL, P = 0.0004 (baseline ≥ 10 ng/mL). In the main and OLE studies, PRO-C3/C3M (matrix metalloproteinase-degraded C3), a marker of net fibrosis formation, was reduced in resmetirom-treated patients (-0.76 [-1.27, -0.24], P = 0.0044 and -0.68, P less then 0.0001, respectively). Resmetirom was well tolerated, with few, nonserious adverse events. Conclusion The results of this 36-week OLE study support the efficacy and safety of resmetirom at daily doses of 80 mg and 100 mg, used in the ongoing phase 3 NASH study, MAESTRO-NASH (NCT03900429). The OLE study demonstrates a potential for noninvasive assessments to monitor the response to resmetirom from an individual patient with NASH.This study aimed to examine whether the diagnostic accuracy of four noninvasive tests (NITs) for detecting advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is maintained or is inferior to with or without the presence of type 2 diabetes. Overall, 874 patients with biopsy-proven NAFLD were enrolled. After propensity-score matching by age, sex, and the prevalence of dyslipidemia, 311 patients were enrolled in each group of with or without diabetes. To evaluate the effect of diabetes, we compared the diagnostic accuracy of the fibrosis-4 (FIB-4) index, the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and type IV collagen 7S (COL4-7S) in patients with NAFLD with and without diabetes. The areas under the receiver operating characteristic curve (AUROC) for identifying advanced fibrosis in patients without diabetes were 0.879 for the FIB-4 index, 0.851 for the NFS, 0.862 for the APRI, and 0.883 for COL4-7S. The AUROCs in patients with diabetes were 0.790 for the FIB-4 index, 0.784 for the NFS, 0.771 for the APRI, and 0.872 for COL4-7S. The AUROC of COL4-7S was significantly larger than that of the other NITs in patients with NAFLD with diabetes than in those without diabetes. The optimal high and low cutoff points of COL4-7S were 5.9 ng/mL and 4.8 ng/mL, respectively. At the low cutoff point, the accuracy of COL4-7S was better than that of the other NITs, especially in patients with diabetes. Conclusion COL4-7S measurement might be the best NIT for identifying advanced fibrosis in NAFLD, especially in NAFLD with diabetes.This is an editorial about non-invasive fibrosis markers in patients with NASH and type 2 diabetes mellitus.

The social pressure placed on smokers today might potentially lead to an increasing level of stress. We investigated if the proportion of persons with high stress level had increased over time more in smokers than in non-smokers.

Data were obtained from repeated cross-sectional surveys of The Capital Region Health Survey conducted in 2010, 2013 and 2017. Survey data were weighted for survey design and non-response, and linked to national register data. Cohens Perceived Stress Scale (PSS-10) score was used. Logistic regression analyses, based on 136608 citizens’ self-reports, were adjusted for sex, age, education level, employment, and alcohol intake (and loneliness, in analysis investigating the associations between tobacco consumption and high stress level).

A significantly higher proportion of citizens reported a high stress level in 2017 compared with 2010 and 2013 but there was not a greater increase in smokers than in non-smokers. Daily smoking men had 69% higher odds of reporting perceived high stress level and daily smoking women had 36% higher odds, than never smokers of the same sex. There was a significant trend between higher daily tobacco consumption and a higher proportion of smokers with high stress level.

The increase in high stress level over time occurred independently of smoking status. Daily smokers had the highest odds of perceived high stress level, and a higher daily tobacco consumption was associated with a higher proportion of smokers with high stress level. Smoking cessation programs should, to a higher degree, consider implementing stress-coping elements to prevent relapse.

The increase in high stress level over time occurred independently of smoking status. Daily smokers had the highest odds of perceived high stress level, and a higher daily tobacco consumption was associated with a higher proportion of smokers with high stress level. Smoking cessation programs should, to a higher degree, consider implementing stress-coping elements to prevent relapse.