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BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.
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Carcinoma Hepatocelular , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Estudios Prospectivos , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
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Coinfección , Várices Esofágicas y Gástricas , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/tratamiento farmacológico , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Bariatric surgery (BS) is the most effective procedure in the management of obesity, achieving a significant decrease in energy intake. AIM: To measure calorie and macronutrient intake in patients subjected to gastric bypass (GBP) or sleeve gastrectomy (SG). MATERIAL AND METHODS: We studied 53 patients subjected to SG and 27 subjected to GBP, who were in the first, second or sixth postoperative month. A food frequency consumption survey was applied by specialized nutritionists and their nutritional status was assessed. RESULTS: Mean calorie intake in months 1, 2 and 6 were 505, 600 and 829.8 kcal, respectively. A significantly higher intake was observed at month 1 in patients with those subjected to SG, compared with GBP patients. Protein consumption was <60 g/d, except at 6 months in patients with GBP. At months 1, 2 and 6, mean consumption of lipids were 17, 28 and 30 g/day, respectively. The figures for carbohydrates were 42, 31 and 77 g/day, respectively. At month 1, patients with GBP had a higher BMI, equalizing at 6 months with those of SG. At 6 months 37% of patients had a normal body mass index and 17% remained obese. A negative correlation was observed between weight loss and energy intake during the first month (rho: -0.40; p = 0.033). CONCLUSIONS: Patients subjected to BS had a low calorie and macronutrient intake in the first six postoperative months. Their calorie intake is negatively associated with weight loss, mainly during the first postoperative month.
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Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Ingestión de Alimentos , Ingestión de Energía , Gastrectomía , Humanos , Obesidad Mórbida/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The existence of psychological distress (PD) during pregnancy is well established. Nevertheless, few studies have analyzed the PD and resilience of mothers and fathers during high-risk pregnancy. This study analyzes the differences between parents' PD and resilience and the relation between them and the neurobehavioral performance of their SGA newborns. METHODS: This prospective study compares two groups of parents and newborns: case group (52 parents and 26 SGA fetuses) and comparison group (68 parents and 34 appropriate-for-gestational-age, AGA, fetuses). In each group, the parents were evaluated during the last trimester of pregnancy, to obtain standardized measures of depression, stress, anxiety, and resilience. At 40 ± 1 weeks corrected gestational age, psychologists evaluated the state of neonatal neuromaturity achieved. RESULTS: Multivariate analysis of variance showed, in gender comparisons, that mothers obtained higher scores than fathers for psychological distress but lower ones for resilience. Similar differences were obtained in the comparison of parents' distress to intrauterine growth by SGA vs. AGA newborns. Mothers of SGA newborns were more distressed than the other groups. However, there were no differences between the fathers of SGA vs. AGA newborns. Regarding neurobehavioral performance, the profiles of SGA newborns reflected a lower degree of maturity than those of AGA newborns. Hierarchical regression analyses showed that high stress and low resilience among mothers partially predict low neurobehavioral performance in SGA newborns. CONCLUSIONS: These findings indicate that mothers of SGA newborns may need psychological support to relieve stress and improve their resilience. Furthermore, attention should be paid to the neurobehavioral performance of their babies in case early attention is needed.
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Padre/psicología , Recién Nacido Pequeño para la Edad Gestacional , Madres/psicología , Resiliencia Psicológica , Estrés Psicológico/psicología , Análisis de Varianza , Estudios de Casos y Controles , Desarrollo Infantil , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Calidad de Vida/psicología , Análisis de RegresiónRESUMEN
BACKGROUND: A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined. METHODS: We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity. RESULTS: At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided. CONCLUSIONS: As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Factores de Riesgo , Taxoides/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.
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Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Antivirales/administración & dosificación , Antivirales/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/efectos adversosRESUMEN
OBJECTIVES: Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS: Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS: Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS: Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.
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Hepacivirus , Hepatitis C , Ácidos Aminoisobutíricos , Antivirales/farmacología , Bencimidazoles , Ciclopropanos , Combinación de Medicamentos , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Estudios Prospectivos , Pirrolidinas , Quinoxalinas , Sulfonamidas , Resultado del TratamientoRESUMEN
(1) Background: this study is based on a model of how changes in protective factors may affect the emotional health of mothers and fathers and thus influence the development of the baby. Our research goal is to determine whether variations in perceived social support moderate levels of stress and depression during pregnancy and/or the effect of parents' emotional health on the baby's anthropometric parameters. (2) Methods: to achieve these aims, a longitudinal study was made of 132 couples and babies, who were evaluated at weeks 12 and 32 of gestation and at birth. Separate analyses were performed for the mothers and fathers, focused on the role of social support in moderating their levels of depression and stress during pregnancy, and the consequent impact on the baby. (3) Results: the results obtained show the moderating effects of changes in social support on maternal and paternal stress and depression. Reduced social support during pregnancy is associated with higher levels of stress and depression in both parents and with a high cephalisation index in their babies. (4) Conclusions: special attention should be paid to social support, which can have a strong impact on the evolution of emotional health during pregnancy and concomitantly on the development of the baby.
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BACKGROUND: Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV. METHODS: Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods. RESULTS: Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition. CONCLUSIONS: After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.
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Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/mortalidad , Humanos , Masculino , Embarazo , Factores de Riesgo , España , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response (SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting. DESIGN: A multicentric prospective cohort study. METHODS: HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5âkPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point. RESULTS: One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7-24) months, ascites 14 (6-29) months, hepatocellular carcinoma (HCC) 17 (11-42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22-38) months (Pâ=â0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) [median (Q1-Q3) time to emergence 12.7 (6.6-28.2) months vs. 25.4 (12.5-41.53) months, respectively (Pâ=â0.026)]. CONCLUSION: The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.
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Carcinoma Hepatocelular , Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cinética , Cirrosis Hepática , Neoplasias Hepáticas/tratamiento farmacológico , Estudios ProspectivosRESUMEN
Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.
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Amitriptilina/farmacología , Carcinoma Hepatocelular/terapia , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Oxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Neoplasias del Cuello Uterino/terapia , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Citotoxinas/farmacología , Reposicionamiento de Medicamentos , Femenino , Citometría de Flujo , Células HeLa , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/fisiología , Especificidad de Órganos , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/análisis , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.
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Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Proteínas no Estructurales Virales/genética , Amidas , Antivirales/efectos adversos , Antivirales/uso terapéutico , Benzofuranos/uso terapéutico , Carbamatos , Ciclopropanos , Farmacorresistencia Viral/genética , Femenino , Genotipo , Hepacivirus/patogenicidad , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Imidazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Quinoxalinas/uso terapéutico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , España/epidemiología , Sulfonamidas , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: Cases of severe unexplained liver disease in HIV-infected individuals have recently been reported and are often associated with exposure to didanosine (ddl) and nodular regenerative hyperplasia. Herein, we examine the clinical outcome following ddl removal. METHODS: From 3,300 HIV-infected patients attending three clinics since 2004, all who exhibited persistently elevated aminotransferases and/or significant liver fibrosis in the absence of any known cause of liver damage were identified. RESULTS: Thirty-two individuals (prevalence approximately 1%) met the inclusion criteria - all were on antiretroviral therapy. Of these, 84% were male and 68% had acquired HIV through homosexual contact. Liver biopsy was performed in 12, of whom three showed nonspecific advanced liver fibrosis, two nodular regenerative hyperplasia and three showed only periportal fibrosis. On follow up, nine patients developed episodes of hepatic decompensation, mainly as a consequence of portal hypertension; in eight cases (25%) portal thrombosis was diagnosed. No association was found with plasma HIV RNA or CD4+ T-cell count. All patients but three had been exposed to ddl for a median of 44 months; removal of ddl in 27 was followed 12 months later by improvement in clinical and laboratory parameters in 13 (48%) patients. Finally, a trend towards liver fibrosis improvement was recognised using FibroScan. CONCLUSIONS: Idiopathic persistent liver enzyme elevations in HIV-infected individuals are often associated with cirrhotic and non-cirrhotic portal hypertension. Although this is a relatively rare condition, prolonged exposure to ddl seems to play a pathogenic role and removal of the drug is associated with clinical and laboratory improvements.
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Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hipertensión Portal/inducido químicamente , Adulto , Femenino , Humanos , Hígado/patología , Masculino , Prevalencia , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the long-term efficacy and safety of didadosine (ddI), lamivudine (3TC), and efavirenz (EFV). This was a follow-up to the VESD study, a 12-month open-label, observational, multicenter study of adult patients with HIV infection who started antiretroviral treatment with the ddI-3TC-EFV once-daily regimen. Of the 167 patients originally included, 106 patients remained on the same triple therapy at the end of the study (1 year), and they were offered an extra 24 months of follow-up; 96 were enrolled in this study (VESD-2). Seventy patients out of the initial cohort were still on the same regimen at month 36, with 97% of them with plasma viral load <50 copies /ml. An intention-to-treat analysis showed that the percentage of patients with plasma viral load <50 copies/ml was 73% at 36 months. CD4 cell counts increased 344 cells/microl over the 36 months. Safety and tolerance were good with no unexpected long-term toxicity. After 3 years of treatment with ddI-3TC-EFV, more than 40% of the patients were still receiving the initial antiretroviral therapy with sustained, durable immunovirological benefit and good acceptance. Long-term toxicity and virological failure were low.
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Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Ciclopropanos , Didanosina/efectos adversos , Quimioterapia Combinada , Estudios de Seguimiento , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Lamivudine/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Resultado del Tratamiento , Carga ViralRESUMEN
Background: Bariatric surgery (BS) is the most effective procedure in the management of obesity, achieving a significant decrease in energy intake. Aim: To measure calorie and macronutrient intake in patients subjected to gastric bypass (GBP) or sleeve gastrectomy (SG). Material and Methods: We studied 53 patients subjected to SG and 27 subjected to GBP, who were in the first, second or sixth postoperative month. A food frequency consumption survey was applied by specialized nutritionists and their nutritional status was assessed. Results: Mean calorie intake in months 1, 2 and 6 were 505, 600 and 829.8 kcal, respectively. A significantly higher intake was observed at month 1 in patients with those subjected to SG, compared with GBP patients. Protein consumption was <60 g/d, except at 6 months in patients with GBP. At months 1, 2 and 6, mean consumption of lipids were 17, 28 and 30 g/day, respectively. The figures for carbohydrates were 42, 31 and 77 g/day, respectively. At month 1, patients with GBP had a higher BMI, equalizing at 6 months with those of SG. At 6 months 37% of patients had a normal body mass index and 17% remained obese. A negative correlation was observed between weight loss and energy intake during the first month (rho: −0.40; p = 0.033). Conclusions: Patients subjected to BS had a low calorie and macronutrient intake in the first six postoperative months. Their calorie intake is negatively associated with weight loss, mainly during the first postoperative month.
Asunto(s)
Humanos , Obesidad Mórbida/cirugía , Derivación Gástrica , Cirugía Bariátrica , Ingestión de Energía , Resultado del Tratamiento , Ingestión de Alimentos , GastrectomíaRESUMEN
OBJECTIVE: To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART. PATIENTS AND METHODS: A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study. RESULTS: Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE. CONCLUSIONS: Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Hígado/efectos de los fármacos , Adulto , Fármacos Anti-VIH/uso terapéutico , Bilirrubina/metabolismo , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hepatitis B Crónica/metabolismo , Hepatitis C Crónica/metabolismo , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Transaminasas/metabolismoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the frequency of transaminase elevations (TE) and total bilirubin elevations (TBE) during the first year of therapy with a single tablet regimen including RPV/FTC/TDF (EPA) in HIV/hepatitis C virus (HCV)-coinfected subjects in clinical practice. METHODS: In a retrospective analysis, HIV/HCV-coinfected subjects who started EPA at 17 centres throughout Spain were included as cases. Subjects who started an antiretroviral therapy (ART) other than EPA during the study period at the same hospitals were randomly selected as controls in a 1:2 ratio. Primary outcome variables were grade (G) 3-4 TE and G4 TBE. RESULTS: Of the 519 subjects included, 173 individuals started EPA. Nine (5.2%) subjects of the EPA group and 49 (14.2%) controls were naïve to ART. The median (Q1-Q3) follow-up was 11.2 (9.7-13.9) months. TE was observed in 2 [1.2%; 95% confidence interval (CI): 0.14%-4.1%] subjects receiving EPA and 11 (3.2%; 95%CI: 1.6%-5.6%) controls (p = 0.136), all events were G3. No patient discontinued ART due to TE. One (0.6%; 95%CI: 0.01%-3.1%) subject on EPA and 8 (2.3%; 95%CI: 1%-4.5%) subjects in the control group developed TBE (p = 0.141), without developing any other hepatic event during follow-up. Three (2.3%) subjects with cirrhosis versus 10 (3.1%) without cirrhosis showed G3-4 TE (p = 0.451). CONCLUSION: The frequency of severe liver toxicity in HIV/HCV-coinfected subjects receiving EPA under real-life conditions is very low, TE were generally mild and did not lead to drug discontinuation. All these data suggest that EPA can be safely used in this particular subpopulation.
Asunto(s)
Antivirales/administración & dosificación , Emtricitabina/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hígado/efectos de los fármacos , Rilpivirina/administración & dosificación , Tenofovir/administración & dosificación , Adulto , Antirretrovirales/administración & dosificación , Bilirrubina/metabolismo , Estudios de Casos y Controles , Coinfección/tratamiento farmacológico , Coinfección/virología , Quimioterapia Combinada , Femenino , Fibrosis/tratamiento farmacológico , Infecciones por VIH/complicaciones , Hepacivirus , Hepatitis C/complicaciones , Hospitalización , Humanos , Hígado/enzimología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España , Comprimidos , Transaminasas/metabolismoRESUMEN
BACKGROUND: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. PATIENTS AND METHODS: This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 µg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. RESULTS: Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. CONCLUSIONS: No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01529073.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Tiazoles/administración & dosificación , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Nitrocompuestos , Proyectos Piloto , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Ribavirina/efectos adversos , Tiazoles/efectos adversos , Resultado del TratamientoRESUMEN
RESUMEN La cirugía bariátrica (CB) ha demostrado ser una alternativa segura y eficaz para la resolución de la obesidad y sus comorbilidades. Parte del éxito de la CB, radica en el manejo nutricional del paciente, para lo que se requiere de un equipo médico-nutricional, entrenado en nutrición bariátrica, con el objetivo de evitar déficit nutricional y modificar hábitos a largo plazo. En la actualidad, no existe en Chile un consenso sobre el protocolo de manejo nutricional pre y post CB. El objetivo del 1er Consenso Chileno de Nutricionistas en Cirugía Bariátrica, es ser una guía para los nutricionistas que asisten a pacientes bariátricos. Este documento resume el trabajo realizado por los Nutricionistas de Sociedad Chilena de Cirugía Bariátrica y Metabólica (SCCBM), quienes durante 5 años trabajaron en reuniones presenciales y comisiones de estudio, revisando evidencias científicas, guías de tratamiento y recomendaciones de expertos, que fundamentarán las recomendaciones alimentario nutricional para cada tema. El resultado es un documento que homologa criterios para el manejo nutricional de pacientes bariátricos y genera los tópicos mínimos para asegurar la atención nutricional de calidad en los equipos bariátricos chilenos.
ABSTRACT Bariatric surgery (BS) has proven to be a safe and effective alternative for the resolution of obesity and its comorbidities. Part of the success of BS lies in the nutritional management of the patient, for which a medical-nutritional team, trained in bariatric nutrition, is required with the aim of modifying long-term habits and avoiding nutritional deficit. At present, there is no consensus in Chile on the pre-and post-BS nutritional management protocol. The objective of the 1st Consensus of Chilean Nutritionists on Bariatric Surgery is to be a guide for nutritionists who assist bariatric patients. This document summarizes the work done by Nutritionists of the Chilean Society of Bariatric and Metabolic Surgery (SCCBM), who, during 5 years, worked in face-to-face meetings and study commissions, reviewing scientific evidence, treatment guides and expert recommendations, which will support nutritional nutrition recommendations for each topic. The result is a document that standardizes criteria for the nutritional management of bariatric patients and generates the minimum topics to ensure quality nutritional care for Chilean bariatric teams.
Asunto(s)
Humanos , Periodo Posoperatorio , Dieta , Micronutrientes , Nutrientes , Cirugía Bariátrica/rehabilitación , Guías como AsuntoRESUMEN
INTRODUCTION: Monotherapy against HIV has undoubted theoretical advantages and has good scientific fundaments. However, it is still controversial and here we will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r) on patients who have received this treatment in our hospitals. MATERIALS AND METHODS: Observational retrospective study that includes patients from 10 Andalusian hospitals that have received DRV/r in MT and that have been followed over a minimum of 12 months. We carried out a statistical descriptive analysis based on the profile of patients who had been prescribed MT and the efficacy and safety that were observed, paying special attention to treatment failure and virological evolution. RESULTS: DRV/r was prescribed to 604 patients, of which 41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had received an average of five lines of previous treatment and had a history of treatment failure to analogues in 33%, to non-analogues 22 and protease inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The simplification was the main criteria for the instauration of MT in the 81.5% and the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6% additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three genotypes were performed after failure without findings of resistance mutations to DRV/r or other IPs. Only 23.7% of patients presented some blips during the period of exposition to MT. Eighty seven percent of all determinations of VL had <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of voluntary decision. Although the average of total and LDL cholesterol increases 10 mg/dL after 2 years of follow-up, so did HDL cholesterol in 3mg/dL and the values of triglycerides (-14 mg/dL) and GPT (-6 UI/mL) decreased. The average count of CD4 lymphocytes increased from 642 to 714/mm(3) at 24 weeks. CONCLUSIONS: In a very broad series of patients obtained from clinical practice, data from clinical trials was confirmed: MT with DRV as a de-escalation strategy is very safe, it's associated to a negligible rate of adverse effects and maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL) is always under 10% and in any case without consequences.