Search Results (8,330)

Enolase-1 (ENO-1) is classically known as a highly conserved glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the final steps of glycolysis. This enzyme, however, is being increasingly implicated as a multifunctional moonlighting protein with compartment-specific roles in inflammation. Within the cytosol, ENO-1 regulates macrophage inflammation during sepsis; on the cell surface, it functions as a plasminogen receptor, and extracellularly, it can participate in innate immune signaling. Across innate and adaptive immunity, ENO-1 has been implicated in macrophage activation, neutrophil recruitment, endothelial cell dysfunction, fibroblast remodeling, and autoantigenicity. These functions have been linked to sepsis, acute respiratory distress syndrome, acute organ injury, hemorrhagic shock, rheumatoid arthritis, and cancer-associated inflammation in the tumor microenvironment. Therapeutic targeting of ENO-1 includes small-molecule inhibitors and monoclonal antibodies. ENO-1, with its compartment-specific functions in disease pathogenesis, serves as a significant therapeutic target for inflammatory diseases. In this review, we discuss the novel compartment-specific roles of ENO-1 in inflammatory diseases, defining its functions beyond its role in glycolysis. We conclude that both the metabolic and moonlighting functions of ENO-1 contribute to inflammation, and future studies should delineate its compartment-specific roles in inflammatory pathophysiology, as compartment-specific targeting may represent the future of ENO-1-directed therapy. Full article

Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney disease, and to examine how specific adipose depots injure the glomerulus and the tubulointerstitium, and then map these mechanisms onto established and emerging therapies. Throughout, obesity-related kidney disease (ORKD) denotes the full spectrum of diposity-driven renal injury, whereas obesity-related glomerulopathy (ORG) is reserved for the biopsy-defined glomerular lesion. Central, visceral, perirenal and renal-sinus adiposity act first through structural and haemodynamic mechanisms, promoting glomerular hyperfiltration, mechanical renal compression and activation of the adipose-derived renin–angiotensin–aldosterone system (RAAS). In parallel, these depots drive cellular and metabolic injury through lipotoxicity, adipokine imbalance, sterile inflammation, oxidative stress, gut dysbiosis, mitochondrial dysfunction, epigenetic remodelling and cellular senescence. Ectopic lipid accumulation within the renal parenchyma—fatty kidney—offers a unifying description of these changes and is most marked in type 2 diabetes mellitus. These interacting processes converge on podocyte stress, tubular metabolic failure, endothelial dysfunction and interstitial fibrosis, producing a phenotypic continuum that ranges from early albuminuria to obesity-related glomerulopathy and progressive CKD. Within the RAAS limb we highlight two comparatively underappreciated, adiposity-linked routes to injury: adipocyte-derived leptin directly upregulates adrenal aldosterone synthase (CYP11B2), and mast-cell chymase generates angiotensin II independently of angiotensin-converting enzyme, together reinforcing aldosterone- and angiotensin II–mediated damage that conventional RAAS blockade only partially interrupts. We further consider the counter-regulatory ghrelin–leptin axis, in which the suppression of ghrelin that accompanies obesity may withdraw an antioxidant, anti-inflammatory and podocyte-protective signal precisely as leptin-driven glomerular injury intensifies, positioning ghrelin as a plausible modulator and candidate biomarker of obesity-related kidney injury. We also examine how obesity complicates renal risk assessment, drug dosing, dialysis delivery and transplant access. Emerging, mechanism-matched therapies—SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, structured lifestyle intervention, metabolic-bariatric surgery and, most recently, aldosterone synthase inhibitors that suppress the chymase- and leptin-driven aldosterone escaping receptor blockade—now enable a precision cardiovascular-kidney-metabolic framework that aligns adipose-depot biology, biomarkers, histology and treatment response to guide mechanism-based care in ORKD. Full article

Background/Objectives: Patients with a clinical diagnosis of severe psoriasis complicated by comorbidities such as cardiovascular disease, obesity, metabolic syndrome and/or with the involvement of high-impact areas constitute a clinical challenge. Tildrakizumab is a monoclonal antibody targeting the IL-23/Th17 axis with a proven record of efficacy and safety in these patients. Methods: Here we present four cases of patients with severe psoriasis and comorbidities including cardiovascular disease (Case 1), obesity (Cases 2 and 3), metabolic syndrome (Case 3), and/or high-impact areas (Cases 2–4). Three patients (Cases 1–3) had previously received biologics but developed secondary failure or loss of efficacy; one patient was bio-naïve (Case 4). Results: The treatment with tildrakizumab in all four patients led to a quick onset (by Week 4 in all cases) of complete and lasting (1 year in Case 1, 4 years in Case 2 and 2 years in Cases 3 and 4) remission with no adverse events reported. Conclusions: Tildrakizumab is a valuable therapeutic option for patients with psoriasis and complex clinical situations, and in particular, in cases with obesity and difficult-to-treat lesion locations such as hands, scalp and genitals. Therapeutic success is often linked to an improvement in patients’ quality of life. Full article

Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to examine the role of vitamin D in the pathophysiology of MetS from a multisystem perspective. Specifically, it synthesizes current evidence on the molecular mechanisms through which vitamin D may influence inter-organ communication, insulin resistance, adipose tissue dysfunction, hepatic metabolism, skeletal muscle function, chronic inflammation, oxidative stress, and mitochondrial homeostasis, highlighting its potential contribution to the prevention and management of MetS. Current evidence indicates that MetS should not be regarded merely as a cluster of isolated metabolic abnormalities but rather as a disorder characterized by disrupted molecular signaling and impaired communication among metabolically active organs. In this context, experimental and preclinical evidence suggests that vitamin D, through activation of the vitamin D receptor (VDR), modulates key signaling pathways, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR-γ), thereby influencing insulin sensitivity, inflammation, oxidative stress, mitochondrial function, and metabolic homeostasis. Nevertheless, clinical evidence remains heterogeneous due, in part, to the lack of consensus regarding serum 25-hydroxyvitamin D thresholds for defining vitamin D status, as well as differences in baseline vitamin D concentrations, supplementation regimens, study populations, and methodological designs. Overall, the available evidence suggests that vitamin D should be considered an adjunct to lifestyle-based interventions rather than a stand-alone therapeutic strategy. Future research is warranted to clarify its clinical utility in the prevention and management of MetS. Full article

High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic stress, inflammation, oxidative injury, renal dysfunction, metabolic disease, and ageing. This biology explains its appeal in ACS, but also its diagnostic limitation: GDF-15 is not cardiac-specific and should not be used as an alternative to electrocardiography and high-sensitivity troponin algorithms for early MI diagnosis. Its better supported role is prognostic. Across emergency department chest pain cohorts, non-ST elevation MI, ST elevation MI, post-ACS trial populations, and serial biomarker studies, higher GDF-15 concentrations are most consistently associated with all-cause mortality, cardiovascular mortality, heart failure, and major bleeding, while associations with recurrent ischemic events alone are less specific. The key unresolved issue is incremental clinical value. GDF-15 may improve discrimination and reclassification beyond clinical predictors, troponin, natriuretic peptides, renal function and GRACE or GRACE 2.0 in selected settings, but statistical association is not equivalent to clinical utility. Its possible role in bleeding risk estimation and antithrombotic benefit–risk assessment is clinically important, especially after the PLATO biomarker analyses, yet routine GDF-15-guided dual antiplatelet therapy decisions remain unsupported. Future implementation requires validated thresholds, calibration, decision curve evidence, health economic evaluation, and trials in which GDF-15-guided management changes care and improves outcomes. Full article

Background/Objectives: Obesity is a major global health challenge characterized by adipose tissue dysfunction, insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and increased cardiometabolic risk. Despite substantial therapeutic advances, limitations related to cost, adverse effects, and long-term adherence have stimulated interest in complementary nutritional approaches. Sulforaphane, a bioactive isothiocyanate derived primarily from broccoli and other cruciferous vegetables, has attracted considerable attention because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This narrative review critically evaluates the current evidence regarding the role of sulforaphane and broccoli-derived preparations in obesity and obesity-associated metabolic dysfunction. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Eligible publications included in vitro, animal, clinical, observational, and relevant review studies investigating sulforaphane, glucoraphanin, or broccoli-derived preparations in relation to obesity, adiposity, insulin resistance, metabolic syndrome, inflammation, oxidative stress, energy metabolism, and related metabolic abnormalities. Results: In vitro studies consistently demonstrate inhibition of adipocyte differentiation and lipid accumulation, attenuation of oxidative stress and inflammatory signaling, and enhancement of cellular energy metabolism. Animal studies further report reductions in adiposity, insulin resistance, hepatic steatosis, oxidative stress, and chronic inflammation, together with improvements in energy expenditure, metabolic flexibility, and obesity-associated metabolic abnormalities. Mechanistic evidence indicates that sulforaphane exerts pleiotropic metabolic effects through activation of the Nrf2 and AMPK pathways, suppression of NF-κB-mediated inflammation, improvement of mitochondrial function, promotion of thermogenesis and adipose tissue browning, regulation of lipid metabolism, and modulation of gut microbiota composition. Human studies, although limited and heterogeneous, suggest possible improvements in glycemic control, insulin sensitivity, endothelial function, and other surrogate metabolic biomarkers associated with obesity. However, evidence demonstrating clinically meaningful reductions in body weight, adiposity, or body composition remains limited and inconsistent, and improvements in these surrogate biomarkers should not be interpreted as evidence of reduced obesity-related morbidity or clinically meaningful adiposity reduction. Bioavailability, myrosinase activity, food processing, gut microbiota composition, and interindividual variability remain important determinants of efficacy and key translational challenges. Conclusions: Current evidence provides strong mechanistic and preclinical support for sulforaphane as a promising candidate adjunctive nutritional intervention for improving obesity-associated metabolic dysfunction. Nevertheless, current human evidence suggests possible metabolic benefits but does not establish sulforaphane as an effective weight-loss intervention or an evidence-based treatment for obesity. Large, long-term randomized controlled trials employing standardized sulforaphane preparations and comprehensive assessments of body weight, adiposity, body composition, metabolic health, pharmacokinetics, and gut microbiota composition are required to establish its clinical efficacy and define its role within precision nutrition strategies for obesity and obesity-associated metabolic dysfunction. Full article

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Cardiovascular disease is a leading cause of morbidity and premature mortality in many inherited syndromic and metabolic disorders. However, its cardiac manifestations are often recognized late and are rarely described collectively within a single cohort. We reviewed eight years of outsourced next-generation sequencing (NGS) requested through the pediatric genetics service of a single tertiary center in Taiwan and identified 22 patients with molecularly confirmed genetic disorders and documented cardiovascular involvement. For each patient, the causative genotype—including lysosomal storage diseases, RASopathies, CHARGE syndrome, connective-tissue disorders, primary cardiomyopathies and channelopathies, neuromuscular disorders, contiguous-gene syndromes, and other metabolic and syndromic conditions—was mapped to a structured echocardiographic phenotype. Septal defects or shunts and valvular regurgitation were the most common findings (10/22 and 9/22, respectively), followed by septal hypertrophy, valvular stenosis, and great-vessel or aortic abnormalities. Two children had left ventricular systolic dysfunction, and one died following an out-of-hospital cardiac arrest. Several cardiac lesions clustered by disease category, most notably valvular thickening in mucopolysaccharidoses and elastin arteriopathy in Williams–Beuren syndrome. These genotype-to-cardiac phenotype patterns support the need for gene-informed, systematic cardiac surveillance rather than symptom-driven referral in children with these disorders. Full article

Objectives: To assess whether muscle morphology and metabolism can inform personalised care in ventral hernias and to define which parts of a proposed postoperative remodelling model are supported by direct evidence. Methods: We conducted a structured narrative review of PubMed/MEDLINE, Scopus and Web of Science from 1 January 2010 through 30 April 2026. Two authors selected 38 publications. Evidence was classified as direct when generated in ventral or incisional hernia cohorts and indirect when drawn from inguinal hernia, transplantation, geriatric, oncological, animal or general muscle studies. No quantitative synthesis was undertaken. Results: Direct studies document lateral muscle displacement, impaired abdominal wall function, inconsistent associations between low muscle mass and clinical outcomes, and CT-derived increases in muscle cross-sectional areas after transversus abdominis release (TAR). The evidence for anterior abdominal wall myosteatosis, biomarker-guided care and the three proposed remodelling trajectories remains largely indirect. In a 37-patient TAR series, the median rectus abdominis cross-sectional area increased by 16.1% (IQR 11.4–27.0%); muscle function and metabolic recovery were not measured. Conclusions: Routine CT can yield muscle area, attenuation and intermuscular adipose tissue measures without further imaging. No anterior abdominal wall-specific thresholds or biomarker cut-offs have been validated, so these measures should not determine current treatment in isolation. Prospective studies should test whether combined imaging, functional and clinical phenotyping improves the selection of prehabilitation and follow-up. Full article

Osteosarcopenia—defined as the coexistence of sarcopenia and osteoporosis—is increasingly recognized as a clinically important geriatric syndrome associated with falls, fractures, frailty, disability, and mortality. Beyond the simple coexistence of bone and muscle loss, emerging data suggest that osteosarcopenia may reflect systemic dysregulation of the bone–muscle–immune–metabolic network. In this narrative review, we synthesize evidence linking inflammaging, immune-cell polarization, mitochondrial dysfunction, nutrient metabolic dyshomeostasis, and gut-derived metabolites to the pathogenesis of osteosarcopenia. Multiple pathological processes—including chronic low-grade inflammation, Th17/Treg imbalance, macrophage polarization, oxidative stress, impaired mitophagy, insulin resistance, ectopic fat accumulation, and altered microbial metabolites—may converge to disrupt bone–muscle crosstalk. Notably, direct evidence from osteosarcopenic populations remains limited, and many mechanistic insights are extrapolated from osteoporosis, sarcopenia, and aging models. We further discuss current and emerging therapeutic strategies, including exercise, nutritional interventions, anti-osteoporotic agents, metabolic modulators, mitochondrial-targeted therapies, and gut-directed approaches. Longitudinal cohorts, multi-omics studies, and randomized controlled trials are urgently required to validate immunometabolic biomarkers and develop integrated interventions for osteosarcopenia. Full article

Background/Objectives: Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets in patients with chronic coronary syndrome (CCS) remains challenging despite intensive lipid-lowering therapy. Bempedoic acid (BA) offers an oral therapeutic option, although data on its clinical performance and patient-level determinants of response in real-world Spanish settings are limited. Methods: We conducted a prospective multicentre study across the four healthcare areas of Cáceres province, Spain, including consecutive CCS patients with LDL-C ≥ 55 mg/dL despite stable intensive lipid-lowering therapy. BA 180 mg/day was added to background treatment. Lipid parameters, metabolic profile, and safety outcomes were assessed after a median follow-up of 28 weeks (IQR 23–47). Multivariable analyses were performed to identify factors associated with of LDL-C reduction and target attainment. A total of 118 patients were analyzed for outcomes. Results: A total of 118 patients (mean age 62.4 ± 10.0 years; 79.2% male) were included. BA reduced LDL-C by 22.8% (−16.36 mg/dL; p < 0.001), enabling 48.3% of patients to achieve LDL-C < 55 mg/dL. Higher baseline LDL-C (β = −0.515; p = 0.001) and the presence of diabetes mellitus (B = 13.8 mg/dL; p = 0.024) were independently associated with greater LDL-C reduction. Notably, 56.3% of patients presented with elevated baseline lipoprotein(a) levels (>50 mg/dL), describing a high underlying burden of residual risk. BA was well tolerated, with a modest increase in uric acid levels but no gout events and a high treatment persistence rate (94.4%). Conclusions: In a real-world CCS population receiving intensive lipid-lowering therapy, BA provides clinically meaningful LDL-C reduction with a favorable safety profile in this multicentre cohort from Cáceres province. Patients with higher baseline LDL-C and diabetes derive greater benefit, supporting a more personalized approach to therapy. These findings reinforce the role of BA in Spanish patients as an intermediate step in lipid-lowering strategies before escalation to more costly therapies, addressing the scarcity of local real-world data. Full article

Insulin resistance (IR) is a well-established metabolic disorder characterized by reduced responsiveness of peripheral tissues to insulin, leading to hyperglycemia and compensatory hyperinsulinemia. Background: In older adults, IR tends to develop gradually and may remain undiagnosed for years due to the insidious nature of the condition, which often lacks overt symptoms. Non-pharmacological interventions refer to the sum of all measures taken in order to improve a certain biological determination or physical parameter and they consist of lifestyle and dietary modifications. Although insulin resistance is recognized as a central mechanism involved in the development of numerous chronic diseases associated with aging, its impact on intrinsic capacity and the mechanisms underlying this relationship are insufficiently synthesized in the literature. In this context, the present narrative review aims to integrate the current evidence on the interaction between insulin resistance and intrinsic capacity, highlighting common biological mechanisms and potential therapeutic and preventive strategies to promote healthy aging. Methods: We conducted a literature search in PubMed, Scopus and Web of Science databases, screening the literature published between 2010 and January 2026. The search strategy included keywords and Boolean operators in order to refine the suggestions. Relevant articles, reviews, studies and guidelines were selected based on their relevance to the objective of this review. Results and Conclusions: The results of the review highlight that insulin resistance represents a central mechanism contributing to the decline in intrinsic capacity through chronic inflammation, oxidative stress, mitochondrial dysfunction and alteration of the gut microbiota. Current evidence suggests that nutritional interventions, in particular the Mediterranean diet and the DASH diet, can improve insulin sensitivity by modulating the microbiota and reducing systemic inflammation, with the potential to contribute to maintaining functional capacity and promoting healthy aging. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC > 1, p < 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS’s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications. Full article

Background/Objectives: Ambient fine particulate matter (PM_2.5) poses significant health risks to older adult populations, yet the specific contributions of its chemical constituents, particularly non-phthalate and non-organophosphate ester compounds, remain poorly understood. This study aimed to elucidate the mechanistic links between PM_2.5-bound ester exposures and metabolic pathway alterations in elderly individuals. Methods: A total of 258 elderly residents aged 60 years or older from Fuzhou, China, were recruited. Personal PM_2.5 exposure was monitored over 72 h using UPAS V2 samplers, with chemical components analyzed via gas chromatography–mass spectrometry (GC–MS). Plasma metabolomic profiling was conducted using liquid chromatography–mass spectrometry (LC–MS), and metabolic pathway enrichment was performed using MetaboAnalyst 5.0. Linear regression models adjusted for covariates (age, sex, BMI, lifestyle factors) assessed associations between ester exposures and metabolite abundance. Results: The mean PM_2.5 concentration was 38.06 μg/m³, with ester compounds dominating the chemical composition. Twenty high-concentration non-target esters were prioritized for analysis. PM_2.5 ester exposure was associated with alterations in key metabolic pathways, including steroid biosynthesis, glycolysis/gluconeogenesis, glycerophospholipid metabolism, and purine/pyrimidine metabolism. When interpreted alongside prior epidemiological evidence, these alterations represent putative links to increased risks of insulin resistance, cardiovascular dysfunction, and metabolic syndrome—relationships that require confirmation in prospective cohort studies and controlled toxicological experiments. Conclusions: Putatively annotated PM_2.5-bound ester compounds, particularly non-regulated subclasses, are associated with systemic metabolic alterations in older adults, coincident with perturbations in steroid and lipid metabolism. While these findings are exploratory and hypothesis-generating, they highlight the need to incorporate specific ester profiles into PM_2.5 risk assessments and develop targeted interventions for vulnerable aging populations. Full article

Introduction: Hepatitis C virus (HCV) infection often coexists with comorbidities, increasing vulnerability, complications, and adverse events. Direct-acting antivirals (DAAs) have dramatically improved HCV management, but they differ in drug–drug interaction (DDI) profiles. Sofosbuvir/velpatasvir (SOF/VEL) is associated with minimal clinically relevant interactions. Areas covered: A narrative review of the literature was conducted by searching PubMed and major international guidelines, focusing on studies published in the DAA era addressing HCV patients with major comorbidities, focusing on diabetes, metabolic syndrome, and cardiovascular disease; neuropsychiatric disorders; cancer; transplants; and use of substances or treatment with opioid agonists; and patients requiring hormone therapy including transgender patients. Expert opinion: Based on the literature and real-world data, managing polypharmacy in HCV patients with comorbidities is effective and well-tolerated, provided thorough drug review, potential DDI analysis, proactive monitoring, and coordinated multidisciplinary care are ensured. DAAs have dramatically improved the management of HCV patients; however, they have different DDI profiles that should be carefully checked. SOF/VEL has been shown to be associated with minimal clinically relevant interactions and offers a simple dosing regimen. DAA treatment is strongly advised in HCV comorbid patients not only to cure HCV but also to improve the course of comorbidities, provided that DDIs are no longer considered mere minor details. Full article