Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults.

This feeding trial evaluated the impact of the Dietary Approaches to Stop Hypertension diet on changes in plasma choline, choline metabolites, and ceramides in obese older adults; 28 adults consumed 3oz (n = 15) or 6oz (n = 13) of beef within a standardized DASH diet for 12 weeks. Plasma choline, betaine, methionine, dimethylglycine (DMG), phosphatidylcholine (PC), lysophosphotidylcholine (LPC), sphingomyelin, trimethylamine-N-oxide (TMAO), L-carnitine, ceramide, and triglycerides were measured in fasted blood samples. Plasma LPC, sphingomyelin, and ceramide species were also quantified. In response to the study diet, with beef intake groups combined, plasma choline decreased by 9.6% (p = 0.012); DMG decreased by 10% (p = 0.042); PC decreased by 51% (p < 0.001); total LPC increased by 281% (p < 0.001); TMAO increased by 26.5% (p < 0.001); total ceramide decreased by 22.1% (p < 0.001); and triglycerides decreased by 18% (p = 0.021). All 20 LPC species measured increased (p < 0.01) with LPC 16:0 having the greatest response. Sphingomyelin 16:0, 18:0, and 18:1 increased (all p < 0.001) by 10.4%, 22.5%, and 24%, respectively. In contrast, we observed that sphingomyelin 24:0 significantly decreased by 10%. Ceramide 22:0 and 24:0 decreased by 27.6% and 10.9% (p < 0.001), respectively, and ceramide 24:1 increased by 36.8% (p = 0.013). Changes in choline and choline metabolites were in association with anthropometric and cardiometabolic outcomes. These findings show the impact of the DASH diet on choline metabolism in older adults and demonstrate the influence of diet to modify circulating LPC, sphingomyelin, and ceramide species.

iPSC-derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function.

Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases. Metabolomic surveys of patient populations and GWAS have linked MacTel to decreased circulating levels of serine and elevated levels of neurotoxic 1-deoxysphingolipids (1-dSLs). However, retina-specific, disease-contributing factors have yet to be identified. Here, we used iPSC-differentiated retinal pigmented epithelial (iRPE) cells derived from donors with or without MacTel to screen for novel cell-intrinsic pathological mechanisms. We show that MacTel iRPE cells mimicked the low serine levels observed in serum from patients with MacTel. Through RNA-Seq and gene set enrichment pathway analysis, we determined that MacTel iRPE cells are enriched in cellular stress pathways and dysregulation of central carbon metabolism. Using respirometry and mitochondrial stress testing, we functionally validated that MacTel iRPE cells had a reduction in mitochondrial function that was independent of defects in serine biosynthesis and 1-dSL accumulation. Thus, we identified phenotypes that may constitute alternative disease mechanisms beyond the known serine/sphingolipid pathway.

Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia.

INTRODUCTION: The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia. OBJECTIVES: Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction. METHODS: Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n [Formula: see text] 5) or LPS (0.375 [Formula: see text]g of LPS/kg of body weight; n [Formula: see text] 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics. RESULTS: Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes. CONCLUSION: Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.

Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet.

Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 µmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.

Obtainment and characterization of a potential functional ingredient from olive.

Current olive oil production methods generate huge amounts of polluting waste, containing most of the health-related compounds in olive. Here, a new product is obtained from olive after pitting, drying and oil extraction, without generating waste. Its characterization showed the presence, within a single matrix, of more than 90% of the polyphenols present in olive, including hydroyxtyrosols (commonly not transferred to olive oil), dietary fiber, oleic acid and polyalcohols. This product is a potential new functional ingredient, consumption of which may lead to additive and/or synergic activities among its constituents; some of which already have approved health claims. Additionally, the olive oil obtained exhibits profiles of fatty acids and phenolic compounds similar to those of commercial olive oil. The procurement of this potential functional ingredient may represent a new approach to the revalorization of olive that additionally decreases waste.

Regular consumption of an antioxidant-rich juice improves oxidative status and causes metabolome changes in healthy adults.

An improvement in oxidative status is associated with a reduction in the incidence of several chronic diseases. However, daily intake of antioxidants in Western diets is decreasing. This study evaluates the effect of daily consumption of an antioxidant-rich juice (ARJ) on oxidative status, cardiovascular disease risk parameters, and untargeted plasma and urine metabolomes. Twenty-eight healthy young adults participated in an 8-week clinical trial by drinking 200 mL of ARJ (pomegranate and grape) daily. At the end of the study, the subjects showed a significant decrease (-29%) in plasma lipid oxidation (malondialdehyde concentration), and a significant increase (+115%) in plasma antioxidant capacity. Plasma and urine metabolomes were also significantly modified and some ions modified in urine were identified, including metabolites of polyphenols, ascorbic acid and biliary acids. No significant changes were observed in lipid profile, inflammation, blood pressure or glycaemia. These results show that incorporating antioxidant-rich beverages into common diets may improve oxidative status in healthy subjects.

Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects.

Current research on dietary antioxidants misses the so-called non-extractable polyphenols (NEPP), which are not significantly released from the food matrix either by mastication, acid pH in the stomach or action of digestive enzymes, reaching the colon nearly intact. NEPP, not detected by the usual analytical procedures, are made up of macromolecules and single phenolic compounds associated with macromolecules. Therefore, NEPP are not included in food and dietary intake data nor in bioavailability, intervention or observational studies. The present paper aims to provide an overview of dietary NEPP - nature, occurrence in diet, metabolic fate and possible health effects. NEPP are a relevant fraction of dietary polyphenols exerting their main biological action in the colon, where they are extensively fermented by the action of microbiota, giving place to absorbable metabolites. NEPP exhibit different potential health-related properties, in particular in relation to gastrointestinal health, such as increases in antioxidant and antiproliferative capacities, reduction of intestinal tumorigenesis and modification of gene expression, as observed in different animal models. Further research into NEPP may provide a better understanding of the health effects of dietary antioxidants.

Beverages have an appreciable contribution to the intake of soluble dietary fibre: a study in the Spanish diet.

Beverages are generally not taken into account to determine the intakes of dietary fibre (DF) in diets. Soluble dietary fibre (SDF) content was determined in common alcoholic and non-alcoholic beverages - ranging from 0.18 g/l in white wine to 9.01 g/l in instant coffee - and their contribution to the DF intake in the Spanish Mediterranean diet was estimated as 2.13 g/person/day. It is concluded that beverages provide an appreciable amount of SDF in the diet, and the omission of its contribution may lead to underestimate DF intakes.

Atypical symptoms of gastro-esophageal reflux during pregnancy.

BACKGROUND: Pregnancy is associated with an increased incidence of heartburn. However, there is no information for other symptoms related to gastro-esophageal reflux (GOR). AIM: to assess the prevalence of atypical symptoms of GOR during pregnancy, and to examine its association with typical GOR symptoms. METHODS: we report data for 263 women with a pregnancy of less than 12 weeks. They were interviewed at the end of each trimester of pregnancy and at 1-year post-partum, using the Gastro Esophageal Reflux Questionnaire (GERQ). In the first interview, information about symptoms in the year before pregnancy was also collected with GERQ. RESULTS: women suffered atypical GOR symptoms during pregnancy more frequently than in the year before: non-cardiac chest pain (NCCP) (9.1 vs. 1.9%), dysphagia (12.6 vs. 2.3%), globus (33.1 vs. 4.6%), cough (26.6 vs. 6.8%), belching (66.2 vs. 19.4%) and hiccups (19.0 vs. 8.4%). Atypical GOR symptoms in pregnancy showed an association with suffering the same symptom before pregnancy and NCCP, globus, belching and hiccups with suffering typical GOR symptoms in the first trimester. CONCLUSIONS: Atypical GOR symptoms are highly prevalent in pregnancy, and are associated with atypical symptoms before pregnancy and with typical symptoms of GOR in the first trimester.

NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease.

Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.

Predictive baseline criteria of primary therapeutic failure in chronic hepatitis C genotype 1.

BACKGROUND AND AIMS: more than half of patients with genotype 1 chronic hepatitis C (CHC) do not achieve a sustained viral response (SVR) to current antiviral therapy due to primary non-response, relapse or intolerance. Factors related to each of these unfavorable outcomes are different and the last two may be partially prevented. Our aim was to identify basal criteria to predict the risk of primary failure. PATIENTS AND METHODS: we included 251 consecutive patients (152 males) from a single centre, infected with HCV genotype 1 and not previously treated. SVR was achieved in 141 patients and primary failure in 110. RESULTS: high vs. low viral load (> 400,000 IU/mL, OR = 6.17; 95% CI: 2.50-15.23), high serum GGT (> 60 IU/mL, OR = 4.25; 95% CI: 2.49-7.24), low serum cholesterol ( < 178 mg/dL, OR = 2.93; 95% CI: 1.75-4.92) and older age (> 47 yrs., OR = 1.79; 95% CI: 1.08-2.96) were associated to the risk of primary failure in the lineal logistic regression analysis. From the 58 patients carrying all the first three negative criteria, 46 (79.3%) were primary non-responders. CONCLUSIONS: the negative basal profile identified in this study is based on easily available data and provides information about the risk of primary therapeutic failure, and may help to decide whether antiviral therapy should be offered to a single patient.

NOD2/CARD15: diferencias geográficas en la población española y su aplicación clínica en la enfermedad de Crohn / No disponible

La enfermedad de Crohn (EC) es una enfermedad complejadesde el punto de vista de la genética puesto que para el desarrollode la enfermedad se tiene que producir una interacción entrefactores genéticos y ambientales. Las mutaciones del genNOD2/CARD15 se han asociado con la susceptibilidad a padecerla EC. El gen NOD2/CARD15 codifica una proteína que actúacomo un receptor intracelular de la proteína dipeptidomuramilque se encuentran en la pared de cubierta de algunas bacterias.Actualmente se desconoce cuál es el papel exacto de estas mutacionesen el funcionamiento de la proteína NOD2/CARD15. Estasmutaciones se han asociado con la localización en intestinodelgado de la enfermedad, el comportamiento fibroestenosante ycon un curso más grave de la enfermedad. Las tres mutacionesasociadas con la EC presentan una distribución desigual entre lasdiferentes razas y áreas geográficas del mundo, con variaciones alo largo de Europa y España. La determinación de las mutacionesdel NOD2/CARD15 no se puede utilizar todavía en la práctica clínica.La principal razón es que estas variantes genéticas sólo incrementanel riesgo de una forma marginal y los podemos identificaren muchos sujetos sanos. Actualmente no se recomiendarealizar estudios de despistaje en familiares de primer grado quepadecen la EC porque no disponemos de ninguna medida preventivapara evitar la enfermedad(AU)

Crohn’s disease (CD) is a genetically complex disease in whichboth genetic susceptibility and environmental factors play key rolesin the development of the disorder. NOD2/CARD15 mutationsare associated with CD. NOD2 encodes for a protein that isan intracellular receptor for a bacterial product (muramyl dipeptide),though the exact functional consequences of these mutationsremain the subject of debate. NOD2/CARD15 mutations are associatedwith ileal CD, with stricturing behavior, and possibly witha more complicated course of CD. NOD2/CARD15 mutationsassociated with CD have demonstrated heterogeneity across ethnicitiesand populations throughout the world, with regional variationsacross Europe and Spain.However, “NOD2/CARD15 testing” is not yet ready for use inthe clinical setting. One of the reasons is that we know that thesegenetic variants increase the risk of disease only marginally, andmany healthy individuals carry the risk alleles, At present it is notrecommended to screen first-degree relatives, because we do nothave the ability to prevent the disease at the present time(AU)

Predictive baseline criteria of primary therapeutic failure in chronic hepatitis C genotype 1

Background and aims: more than half of patients with genotype 1 chronic hepatitis C (CHC) do not achieve a sustained viral response (SVR) to current antiviral therapy due to primary non-response, relapse or intolerance. Factors related to each of these unfavorable outcomes are different and the last two may be partially prevented. Our aim was to identify basal criteria to predict the risk of primary failure. Patients and methods: we included 251 consecutive patients (152 males) from a single centre, infected with HCV genotype 1 and not previously treated. SVR was achieved in 141 patients and primary failure in 110. Results: high vs. low viral load (> 400,000 IU/mL, OR = 6.17; 95% CI: 2.50-15.23), high serum GGT (> 60 IU/mL, OR = 4.25; 95% CI: 2.49-7.24), low serum cholesterol (< 178 mg/dL, OR = 2.93; 95% CI: 1.75-4.92) and older age (> 47 yrs., OR = 1.79; 95% CI: 1.08-2.96) were associated to the risk of primary failure in the lineal logistic regression analysis. From the 58 patients carrying all the first three negative criteria, 46 (79.3%) were primary non-responders. Conclusions: the negative basal profile identified in this study is based on easily available data and provides information about the risk of primary therapeutic failure, and may help to decide whether antiviral therapy should be offered to a single patient(AU)

STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility.

STAT3 (signal transducer and activator of transcription 3) signaling is a critical component of Th17-dependent autoimmune processes. Genome-wide association studies (GWAS) have revealed the role of the STAT3 gene in inflammatory bowel disease (IBD) susceptibility, although confirmation in clinical subphenotypes is warranted. Mice with targeted deletion of Stat3 in T cells are resistant to experimental autoimmune encephalomyelitis, which is a multiple sclerosis (MS) model. Moreover, increased phosphorylated STAT3 was reported in T cells of patients evolving from clinically isolated syndrome to defined MS and in relapsing patients. These evidences led us to analyze the role of STAT3 in Crohn's disease (CD), ulcerative colitis (UC) and MS risk. Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls. The haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD (CD: P=0.005, odds ratio 1.25, 95% confidence interval 1.06-1.46; and UC: P=0.002, odds ratio 1.19, 95% confidence interval 1.02-1.38). No evidence of association was detected for MS. The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population. A major role of this gene in MS seems unlikely.

Onset and disappearance rates of gastroesophageal reflux symptoms in the Spanish population, and their impact on quality of life.

BACKGROUND: few studies have reported the onset and disappearance rates of gastroesophageal reflux symptoms (GERS) in the population. AIM: to assess the occurrence and disappearance rates of GERS in Spain, and their impact on health-related quality of life (HRQL). PARTICIPANTS AND METHODS: participants were selected at random from the general population of Madrid in age and sex strata. They were interviewed at home twice, 6 months apart. Heartburn, acid regurgitation and consultation were assessed with the gastroesophageal reflux questionnaire, and HRQL with the SF-36. RESULTS: 709 individuals were included, and 451 (63.6%) were re-interviewed 6 months later. Among the 325 individuals without GERS, 9 developed weekly symptoms (2.2% [95% CI: 0.8, 3.4%]); 2 (22%) consulted because of GERS. Among the 34 subjects reporting weekly GERS initially, 26 did not report them at 6-months. Onset of GERS was associated with worsening scores in the physical summary of SF-36 (delta = -6.6 [95% CI: -11.8, -1.42]), while disappearance with an improved score (delta = -3.0 [95% CI: 0.0, 5.9]). CONCLUSION: despite the lower prevalence of GERS in Spain, the occurrence rate is 2.2% in 6 months; however symptoms disappeared in more than half of subjects six months later. Developing GERS was associated with reduced HRQL, and their disappearance with improvement.

Effect of BSN-MST1 locus on inflammatory bowel disease and multiple sclerosis susceptibility.

Genome-wide studies highlighted the effect in Crohn's disease (CD) and ulcerative colitis (UC) susceptibility of single nucleotide polymorphisms (SNPs) in 3p21, where BSN (bassoon), MST1 (macrophage stimulating-1) and MST1R (MST1 Receptor) genes map. MST1R expression was significantly downregulated in multiple sclerosis (MS) compared with control brains, resembling findings in the MS mouse model. We pursued to replicate the effect of this locus on inflammatory bowel diseases and to evaluate its contribution to MS risk. Polymorphisms rs9858542, rs2131109 and rs1128535 were analysed by TaqMan assays in Spanish patients (370 CD, 405 UC and 415 MS) and 800 ethnically matched controls. Allele frequencies of these SNPs were significantly different in CD patients compared with controls [rs9858542: P=0.001, Odds ratio (OR)=1.35; rs2131109: P=0.0005, OR=1.37; rs1128535: P=0.007, OR=0.78] and, specifically, in the ileal phenotype [rs9858542: P=0.0004, OR=1.47; rs2131109: P=0.00009, OR=1.52; rs1128535: P=0.02, OR=0.69]. No differences were detected between UC or MS patients and control individuals. The effect of this locus on CD predisposition was replicated, but no influence on UC or MS predisposition could be detected. This susceptibility locus seems to affect mainly to the ileal CD subphenotype, although this point awaits further corroboration in independent cohorts.

Onset and disappearance rates of gastroesophageal reflux symptoms in the Spanish population, and their impact on quality of life

Background: few studies have reported the onset and disappearancerates of gastroesophageal reflux symptoms (GERS) inthe population.Aim: to assess the occurrence and disappearance rates ofGERS in Spain, and their impact on health-related quality of life(HRQL).Participants and methods: participants were selected atrandom from the general population of Madrid in age and sexstrata. They were interviewed at home twice, 6 months apart. Heartburn,acid regurgitation and consultation were assessed withthe gastroesophageal reflux questionnaire, and HRQL with theSF-36.Results: 709 individuals were included, and 451 (63.6%)were re-interviewed 6 months later. Among the 325 individualswithout GERS, 9 developed weekly symptoms (2.2% [95% CI:0.8, 3.4%]); 2 (22%) consulted because of GERS. Among the 34subjects reporting weekly GERS initially, 26 did not report themat 6-months. Onset of GERS was associated with worseningscores in the physical summary of SF-36 (delta = -6.6 [95%CI: -11.8, -1.42]), while disappearance with an improved score(delta = -3.0 [95% CI: 0.0, 5.9]).Conclusion: despite the lower prevalence of GERS in Spain,the occurrence rate is 2.2% in 6 months; however symptoms disappearedin more than half of subjects six months later. DevelopingGERS was associated with reduced HRQL, and their disappearancewith improvement(AU)

Bioavailability of phenolic antioxidants associated with dietary fiber: plasma antioxidant capacity after acute and long-term intake in humans.

Most studies on bioavailability of phenolic antioxidants are focused in foods and beverages in which they may be easily released from the food matrix, reaching a peak in plasma antioxidant capacity 1-2 h after the intake. However, plant foods contain significant amounts of polyphenols associated with dietary fiber. The aim of the present work was to seek the bioavailability of total phenolic antioxidants associated with dietary fiber by measuring plasma antioxidant capacity in human volunteers. An acute intake of 15 g of a dietary fiber rich in associated phenolic antioxidants in healthy volunteers (n = 10) increased antioxidant capacity of plasma in relation to a control group (n = 4), becoming significant 8 h after the intake. This shows that phenolic antioxidants associated with dietary fiber are at least partially bioavailable in humans, although dietary fiber appears to delay their absorption. No significant changes were observed after long-term intake (16 weeks, 34 subjects).

Oscillations in serum ferritin associated with antiviral therapy in chronic hepatitis C.

BACKGROUND: Hyperferritinemia is often found in patients with chronic hepatitis C (CHC) and is predictive of poorer response to antiviral therapy. OBJECTIVE: To investigate changes in ferritinemia during and after antiviral therapy. PATIENTS AND METHODS: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.5 years +/- 10.1) before and during antiviral therapy, and six months post-treatment in all 154 patients with undetectable serum HCV-RNA after therapy completion. RESULTS: Baseline serum ferritin was higher in patients with primary therapeutic failure than in those reaching sustained viral response (330 +/- 291 ng/mL vs. 211 +/- 192 ng/mL, p = 0.002). Serum ferritin transiently increased during therapy from baseline (257 +/- 242 ng/mL vs. 875 +/- 630 ng/mL, p < 0.001). Six months after finishing therapy, serum ferritin decreased under baseline values both in sustained responders (117 +/- 102 ng/mL vs. 211+/- 192 ng/mL, p < 0.001) and, to a lesser extent, in relapsers (217 +/- 174 ng/mL vs. 257 +/- 221 ng/mL, p = 0.047). CONCLUSIONS: Baseline serum ferritin may predict response to antiviral treatment in chronic hepatitis C. Combined antiviral therapy induces a marked increase in serum ferritin that falls below baseline values after sustained viral response, suggesting that the cause of hyperferritinemia in many patients is HCV infection itself rather than iron overload.

Oscilaciones de la ferritina sérica asociadas al tratamiento antiviral en la hepatitis crónica por virus C / Oscillations in serum ferritin associated with antiviral therapy in chronic hepatitis C

Antecedentes: la hiperferritinemia es frecuente en los enfermoscon hepatitis crónica C (HCC) y reduce las probabilidades derespuesta al tratamiento antiviral.Objetivo: investigar las variaciones de la ferritina sérica durantey después del tratamiento y su relación con la respuesta al mismo.Pacientes y métodos: la ferritina sérica se ha medido en262 enfermos con HCC (163 hombres, edad media 48,5 años ±10,1) antes y durante el tratamiento antiviral, y a los 6 meses definalizado en los 154 enfermos con viremia indetectable al finaldel tratamiento.Resultados: la ferritina sérica basal era más alta en enfermoscon fracaso terapéutico primario que en los que consiguieron respuestaviral sostenida (RVS) (330 ± 291 ng/ml vs. 211 ± 192ng/ml, p = 0,002). La ferritina sérica aumentó transitoriamentedurante el tratamiento (257 ± 242 ng/ml vs. 875 ± 630 ng/ml, p< 0,001). La ferritina sérica descendió a valores inferiores a losbasales seis meses después de finalizado el tratamiento en los pacientescon RVS (117 ± 102 ng/ml vs. 211± 192 ng/ml, p <0,001) y, en menor grado, en los que sufrieron recidiva viral (217± 174 ng/ml vs. 257 ± 221 ng/m, p = 0,047).Conclusiones: una ferritina sérica basal elevada se asocia conmayor riesgo de fracaso terapéutico en la HCC. El tratamientoantiviral induce un marcado incremento de la ferritina sérica quevuelve a valores por debajo de los basales en los enfermos que obtienenRVS. Esto sugiere que la causa de hiperferritinemia en lamayoría de los enfermos es la propia infección por VHC y no lasobrecarga de hierro(AU)

Background: hyperferritinemia is often found in patients with chronic hepatitis C (CHC) and is predictive of poorer response to antiviral therapy. Objective: to investigate changes in ferritinemia during and after antiviral therapy. Patients and methods: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.5 years ± 10.1) before and during antiviral therapy, and six months post-treatment in all 154 patients whit undetectable serum HCV-RNA after therapy completion. Results: baseline serum ferritin was higher in patients with primary therapeutic failure than in those reaching sustained viral response (330 ± 291 ng/mL vs. 211 ± 192 ng/mL, p = 0.002). Serum ferritin transiently increased during therapy from baseline (257 ± 242 ng/mL vs. 875 ± 630 ng/mL, p < 0.001). Six months after finishing therapy, serum ferritin decreased under baseline values both in sustained responders (117 ± 102 ng/mL vs. 211± 192 ng/mL, p < 0.001) and, to a lesser extent, in relapsers (217 ± 174 ng/mL vs. 257 ± 221 ng/mL, p = 0.047). Conclusions: baseline serum ferritin may predict response to antiviral treatment in chronic hepatitis C. Combined antiviral therapy induces a marked increase in serum ferritin that falls below baseline values after sustained viral response, suggesting that the cause of hyperferritinemia in many patients is HCV infection itself rather than iron overload(AU)