Statins and non-alcoholic fatty liver disease

Dear Editor, In April 9 issue, van den Berg et al1 report interesting results on the indication for lipid‐lowering treatment in a large cohort with suspected non‐alcoholic fatty liver disease (NAFLD) within the population‐based Lifelines Cohort Study. Fatty liver index (FLI) ≥60 was used as a proxy of NAFLD and the NAFLD fibrosis score (NFS) to identify the NAFLD patients with suspected advanced fibrosis. Cardiovascular disease (CVD) risk was established by the 2016 European society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias.2 Subjects with FLI ≥ 60 (suspected NAFLD) had an increased 10‐ year predicted cardiovascular risk compared to those with FLI < 60 with an approximately 2 times higher need for statin therapy based on CVD risk prediction and their LDL cholesterol level. Subjects with a FLI ≥ 60 were more likely to be classified with type 2 diabetes, Metabolic Syndrome (MetS), history of CVD and impaired renal function. Interestingly, estimated 10‐year very high cardiovascular risk was approximately 4 times higher in subjects with a NFS > 0.676 compared to those with the absence of advanced fibrosis. Finally, indication for statin treatment was positively associated with a FLI ≥ 60 after controlling for age, sex, current smoking, impaired renal function, and the presence of MetS and its individual components. The above results have an even greater relevance if we consider that all the subjects who were already on statin therapy were subtracted from the analysis. These findings may have an important clinical relevance and emphasize the need for effective treatment with statins in patients with NAFLD. Indeed, accumulating evidence suggests that CVD, rather than liver disease, dictates the outcomes in NAFLD.3 Besides, in most subjects NAFLD constitutes the hepatic component of MetS and numerous patients have atherogenic dyslipidemia. This study further supports the results of a previous study by our group where under prescription of statins in patients with NAFLD was observed.4 In fact, mild liver enzyme elevation remains a concern and despite its proven efficacy and safety,5 statin administration is sometimes limited by the worry about related side effects. Indeed, there is a tendency of general physicians to discourage statin use in patients with baseline elevation of serum liver enzymes and/ or to discontinue medication when minor alterations were appreciated. Of note, in our study, statin under‐use was high also in patients at very high CV risk such as those with a previous CV event. This study by van den Berg et al further stresses the issue of under prescription of statins in people with NAFLD and indication for treatment, based on CV risk class and low‐density lipoprotein cholesterol target according to ESC/EAS guidelines

Second cohomology groups and finite covers

For D an infinite set, k>1 and W the set of k-sets from D, there is a natural closed permutation group G_k which is a non-split extension of \mathbb{Z}_2^W by \Sym(D). We classify the closed subgroups of G_k which project onto \Sym(D)$. The question arises in model theory as a problem about finite covers, but here we formulate and solve it in algebraic terms.Comment: Typos corrected; change of title to 'Second cohomology groups and finite covers of infinite symmetric groups' in published versio

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p < 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p < 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

SEISMIC ANISOTROPY AND MICRO-SEISMICITY IN THE UPPER CRUST AT NORTH OF GUBBIO BASIN (CENTRAL ITALY): RELATION WITH THE SUBSURFACE GEOLOGICAL STRUCTURES AND THE ACTIVE STRESS FIELD

During the months of April and May 2010, a seismic sequence (here named “Pietralunga seismic sequence”) took place in the northeastern part of the Gubbio basin (Northern Apennines); this area is well known to be interested by a continuous background micro-seismic activity. The sequence was recorded both by the INGV National Seismic Network, and by the stations installed by the Project “AIRPLANE” (financially supported by MIUR-Italian Ministry of Education and Research) with the aim of investigating the seismogenetic processes in the Alto Tiberina Fault (ATF) system region. In this work we present the anisotropic results at four stations: ATFO, ATPC, ATPI, ATVO located around the northern termination of the Gubbio basin that well delimit both the seismic se- quence and the whole 2010 seismicity (about 2500 events). The study of seismic anisotropy has provided useful information for the interpretation and evaluation of the stress field and active crustal deformation. Seismic anisotropy can yield valuable information on upper crustal structure, fracture field, and presence of fluid-saturated rocks. Moreover, the large number of seismic waveforms recorded especially during the Pietralunga sequence allows us also to study the spatio-temporal changes of anisotropic parameters to better understand its evolution and the possible correlation to the presence and migration of fluids

Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

Assessment of SPLAT formulations to control Grapholita molesta (Lepidoptera:Tortricidae) in a Brazilian apple orchard.

Mating disruption is a technique that uses synthetic copies of sex pheromones to control insect pests. We aimed to control Oriental fruit moth (OFM) Grapholita molesta (Busck) (Lepidoptera: Tortricidae) with formulations of SPLAT Grafo (SG) and SPLAT Grafo Attract and Kill (SGAK) in small (1 ha) apple (Malus domestica Borkh.) orchards. Our experiment was conducted in a commercial orchard with Gala trees (spacing 1.5 × 4.5 m) in Vacaria, Rio Grande do Sul State, Brazil. We evaluated the effect of four treatments on G. molesta population densities: a) SG at 1 kg ha-1 (300 point sources of 3.3 g each), b) SGAK at 1 kg ha-1 (1000 point sources of 1 g each), c) insecticides as recommended by Integrated Apple Production (IAP), and d) untreated control (no treatment). Specialized Pheromone and Lure Application Technology (SPLAT) treatments were applied on 1 August 2004 and reapplied after 120 d (1 December 2004). The treatment effect was evaluated by weekly counts of males captured in Delta traps baited with commercial synthetic sex pheromone lures (eight traps per treatment). We assessed fruit damage caused by G. molesta in eight replicates of 200 fruits each on 26 October, 30 November 2004, and 5 and 31 January 2005. Applying 1 kg ha-1 of SG and SGAK in August and December 2004 significantly reduced the number of male moths caught in Delta traps. Damage to fruits at harvest, however, did not differ significantly from the control. This indicates a decline in the efficacy of mating disruption when SG and SGAK are used to protect small areas (1 ha) under high Oriental fruit moth pressure

Von willebrand and factor VIII portosystemic circulation gradient in cirrhosi. Implications for portal vein thrombosis

OBJECTIVES: Portal vein thrombosis seems to be dependent on local hypercoagulation and venous stasis; data regarding endothelial damage are lacking. METHODS: von Willebrad factor, a marker of endothelial damage/perturbation, factor VIII, and lipopolysaccharides (LPS) were studied in the portal and systemic circulation of 20 cirrhotic patients undergoing transjugular intrahepatic portosystemic procedure. RESULTS: von Willebrad factor, factor VIII, and LPS were higher in the portal compared with systemic circulation, with a significant correlation between LPS and the other 2 variables. DISCUSSION: Endothelial damage and hypercoagulation coexist in the portal tree of patients with cirrhosis, and both could contribute to portal vein thrombosis. LPS may be a potential trigger of endothelial damage

Feromônios sexuais no manejo de insetos-praga na fruticultura de clima temperado.

bitstream/item/95271/1/Feromonios-ULTIMA-VERSAO-08-07-2013.pdf; bitstream/item/95273/1/Capa-Feromonios.pd