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Background and aims The heterogeneity and mechanisms of multifactorial chylomicronemia (MCM) remain poorly understood. To gain new insights, post heparin lipolysis measured at 60 min (PHLA60), in addition to the more commonly used 10 min (PHLA10), was assessed in patients with history of MCM. Methods 62 consecutive MCM patients were studied. The evaluation included LPL, APOC2, APOA5, GPIHBP1, LMF1 and APOE gene sequencing, as well as pre- and post-heparin injection biochemical analysis, including lipid profiles, determination of apolipoprotein B, B-48, CII, CIII, lipoprotein lipase (LPL) concentrations (LPLC0, LPLC10 and LPLC60) and post-heparin LPL activity (PHLA10 and PHLA60). Results In controls, PHLA60 did not differ from PHLA10, while in MCM patients, PHLA60 was significantly lower than PHLA10 ( p <0.001). PHLA60 showed a bimodal distribution in MCM patients ( p =0.03). One subgroup exhibited PHLA60 similar to controls, with persistent lipoprotein remodeling and, paradoxically, the highest basal plasma TG concentration. APOE ε4 was over-represented compared to the European population ( p <0.05) and Apo CIII/Apo B ratio was increased ( p <0.01). The other subgroup exhibited low PHLA60 ( p <0.001) compared to both controls and the other MCM subgroup with a lipoprotein profile consistent with fast and transient remodeling. LMF1 p. Arg364Gln was over-represented compared to the European population ( p <0.05). Conclusions The study showed that PHLA60 identifies a subgroup of MCM with a defect in lipolysability and/or hepatic clearance of triglycerides-rich lipoproteins, and a larger one with a defect in LPL availability. These findings provide new insights into the heterogeneity of MCM and might contribute to adjust treatment targeting. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: CC received consultant fees from Gilead, Novo Nordisk, AstraZeneca, Lilly, E-scopics, MSD, Bayer, Corcept and Echosens; grant support from Gilead, Echosens and Novo Nordisk.

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach., Competing Interests: Competing interests: CC received consultant fees from NovoNordisk, AstraZeneca, Gilead. J-FD Advisory committees: Bayer, BMS, Falk, Genfit, Genkyotex, Gilead Science, HepaRegenix, Intercept, Eli Lilly, Merck, Novartis; Speaking and teaching: Bayer, BristolMyers Squibb, Intercept, Genfit, Gilead Science, Novartis. RL serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myer Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also cofounder of Liponexus., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Controlled attenuation parameter (CAP) measurements using M probe have been reported to be lower than those of the XL-probe in detection of hepatic steatosis. However, there has been no direct comparison of CAP with the M vs the XL probe in patients with nonalcoholic fatty liver disease (NAFLD). We compared CAP with the M vs the XL probe for quantification of hepatic fat content, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the standard., Methods: We performed a prospective study of 100 adults (mean body mass index [BMI], 30.6 ± 4.7 kg/m2) with and without NAFLD, assessed by CAP with the M probe and XL probe on the same day, at a single research center, from November 2017 through November 2018. We then measured the MRI-PDFF as the reference standard. Outcomes were presence of hepatic steatosis, defined as MRI-PDFF ≥ 5%, and detection of hepatic fat content ≥ 10%, defined as MRI-PDFF ≥ 10%. We performed area under the receiver operating characteristic curve (AUROC) analyses to assess the diagnostic accuracy of CAP for each probe in detection of hepatic steatosis (MRI-PDFF ≥ 5%) and of hepatic fat content ≥ 10%., Results: Of the study participants, 68% had an MRI-PDFF of 5% or more and 48% had an MRI-PDFF of 10% or more. The mean CAP measured by the M probe (310 ± 62 db/m) was significantly lower than by the X probe (317 ± 63 db/m) (P = .007). When M probe was used in participants with BMIs <30 kg/m 2 and XL probe in participants with BMIs ≥30 kg/m 2 , the CAP measured by the M probe (312 ± 51.4 db/m) remained significantly lower than that of the XL probe (345 ± 47.6 db/m) (P = .0035.), when the MRI-PDFF was above 5%. The optimal threshold of CAP for the detection of MRI-PDFF≥5%, was 294 db/m with the M probe and 307 db/m with the XL probe. The optimal threshold of CAP for the detection of MRI-PDFF ≥ 10%, was 311 db/m with the M probe and 322 db/m with the XL probe. For only the XL probe, CAP measurements with an interquartile range below 30 dB/m detected an MRI-PDFF≥5% with a lower AUROC (0.97; 95% CI, 0.80-1.00) than CAP measurements with an interquartile range above 30 dB/m (AUROC, 0.82; 95% CI, 0.71-0.90) (P = .0129)., Conclusions: In an analysis of the same patients using CAP with the M probe and XL probe, with MRI-PDFF as the standard, we found that the M probe under-quantifies CAP values compared with the XL probe, independent of BMI. The type of probe should be considered when interpreting CAP data from patients with NAFLD., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (DM2). 1 Accurately assessing CVD risk in NAFLD patients is critical to improving clinical outcomes. 1 Use of liver stiffness measurements to noninvasively assess for liver fibrosis is broadening, and magnetic resonance elastography (MRE) is the most accurate modality in NAFLD. 2 However, the association between fibrosis severity on MRE and the degree of CVD risk is unknown. The aim of this study was to determine whether MRE-assessed liver fibrosis stage is associated with CVD risk determined by Framingham risk score (FRS) and coronary artery calcium (CAC)., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Statins in secondary prevention of cardiovascular risk. After 25 years of clinical trial Statin efficacy is well established in secondary prevention of cardiovascular risk data. The recent guidelines recommend the use of high-intensity statin therapy in order to reach an LDL-cholesterol (LDL-c) concentration under 0.70g/L. Nevertheless, the effectiveness of this strategy remains unclear. Indeed, the number of patients to treat to avoid one cardiovascular event increases while the LDL-c threshold is decreased. Statin efficacy depends on different factors including inter-individual statin response, tolerance and therapeutic observance certainly improved is secondary prevention compared to primary prevention. Finally, the optimal LDL-c target to reach beyond 0.70 g/L remains unknown and the development of new but expansive treatments will bring more complexity in the management of the optimal strategy in secondary prevention., Competing Interests: C. Caussy déclare avoir été prise en charge lors de congrès par Lilly, Servier et Ipsen. S. Charrière déclare avoir fait des interventions ponctuelles pour AstraZeneca, Boehringer-Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi et Servier, des essais cliniques pour Novartis, et avoir été prise en charge lors de congrès par AstraZeneca, Lilly, MSD, Novo Nordisk, Nutricia, Roche Diagnostics et Servier. P. Moulin déclare déclare avoir fait des interventions ponctuelles et des essais cliniques pour Aegerion, Amgen, AstraZeneca/BMS, Regeneron et Sanofi.