👤 Katherine Byrnes

Chronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV eradication on serum lipid and lipoprotein profiles and CVD risk during and following direct-acting antiviral (DAA) therapy. We retrospectively analysed stored sera and plasma from 60 DAA-naïve patients, genotypes 1-4, treated with 12 weeks of sofosbuvir-velpatasvir. Serum lipids, apolipoproteins (apo), and a systemic inflammatory marker, GlycA, were measured serially beginning early on treatment and off treatment. Additionally, NMR LipoProfile analysis was performed on plasma samples. Expression of genes regulating lipid metabolism was assessed from paired liver biopsies obtained before and on treatment. Linear mixed models were used to examine changes in lipid and inflammatory markers; Framingham and ASCVD CVD risk scores were assessed before and after treatment. Decline in HCV viremia was associated with a rapid, significant increase in TChol, HDL-C, LDL-C, ApoA-1 and ApoB, and GlycA, improvement in ALT, hepatic inflammation, and steatosis but no change in glycemic control (HOMA-IR and HbA1c). Increase in TChol, LDL-C, and ApoB was associated with an increased SREBP1expression. Both ASCVD and Framingham risk scores were significantly increased at week 24 post treatment after adjusting for age (p < 0.0001). Serum lipids and lipoproteins rapidly increase with inhibition of viral replication during DAA therapy, an effect that may be mediated by genes affecting hepatic de novo lipogenesis. Based on lipid changes, HCV eradication may increase CVD risk, but this needs to be investigated prospectively. Show less

Pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are elevated in response to psychosocial stress; however, less is known about other inflammatory markers. We explored response to the Trier Social Stress Test (TSST) of 16 cytokines and growth factors in patients with major depressive disorder (MDD, n = 12) vs. healthy volunteers (HV, n = 16). Outcomes were baseline and post-stress levels estimated by area under the curve (AUC Baseline concentrations were higher in MDD for platelet-derived growth factor (PDGF)-AB/BB (p = 0.037, d = 0.70), granulocyte-macrophage colony-stimulating factor (GM-CSF, p = 0.033, d = 0.52), and IL-8 (p = 0.046, d = 0.74). After TSST, AUC Effect sizes were robust in this exploratory study, although interpretation of the results must be cautious, given small sample size and multiple comparisons. Differential study of stress-induced biomarkers may have important ramifications for MDD treatment. Show less

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ that governs body energy metabolism. Autophagy's role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders. Show less