Experiencia en práctica clínica real con los nuevos antivirales de acción directa en hepatitis crónica C / Experience in real clinical practice with new direct acting antivirals in chronic hepatitis C

Introducción y objetivo: La inclusión en práctica real de los antivirales de acción directa en pacientes con hepatitis crónica por VHC ha supuesto un hito histórico en Medicina. Pacientes y métodos: Estudio analítico, prospectivo que incluyó 126 pacientes con hepatitis crónica por VHC tratados con antivirales de acción directa. Evaluamos la eficacia y seguridad del tratamiento y factores asociados a fracaso terapéutico. Resultados: Edad 54±10 años. Varón (70%). Cirrosis (60%). Distribución según genotipos: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B y C (n=15). Naïve (56%). Tasa RVS fue (87,3%): Child-A (91%), Child-B (75%) y Child-C (60%). Las mejores tasas de curación se alcanzaron con las combinaciones Combo 3D/2D±ribavirina (RVS=97,4%; n=39) y sofosbuvir/ledipasvir±ribavirina (RVS=93,1%; n=29). Tasas<90% se registraron con: sofosbuvir+simeprevir±ribavirina (RVS=88%; n=25), simeprevir+daclatasvir±ribavirina (RVS=78%; n=18) y sofosbuvir+daclatasvir±ribavirina (RVS=73,3%; n=15). La adicción de ribavirina a estas 3 últimas opciones terapéuticas (n=19) mejoraba las tasas de curación (RVS=94,7%; 18/19) frente a su ausencia (n=39; RVS=77%). Mejoría MELD (40%). Salida lista trasplante (20%). Sustituciones asociadas a resistencias NS3: G1a (posiciones 80K; n=5); G1b y G4 (posición 168 y 36; n=4), mientras para NS5a: G1a (posición 30; n=2) y G1b y G3 (posición 93; n=3). Variables asociadas al fracaso en análisis multivariante (p<0,05): presencia de ascitis, G3 y dosis de ribavirina<600mg/día. Discusión: La presencia de genotipo 3, ascitis o dosis de ribavirina<600mg/día se asoció a mayores tasas de fracasos. Sería recomendable el uso de ribavirina≥600mg/día en cirróticos G1 o G3, que vayan a ser tratados con sofosbuvir+simeprevir o daclatasvir, si no hubiese disponibilidad de un test de resistencia basal (AU)

Introduction and objective: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. Patients and methods: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. Results: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. Discussion: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available (AU)

Physical activity domains and risk of gastric adenocarcinoma in the MCC-Spain case-control study.

BACKGROUND: Evidence for a protective role of physical activity against development of stomach cancer is yet inconclusive. We studied the association of domain-specific physical activity and the risk of gastric adenocarcinoma (GAC), by site and histology, in the MCC-Spain case-control study. METHODS: 428 histologically confirmed GAC cases (67% men) including the gastro-esophageal region and 3225 controls were included. Cases were recruited in hospitals from 10 different Spanish regions, whereas population controls were randomly selected within the respective hospitals' catchment areas. A physical activity (PA) questionnaire was used to gather information on household and recreational activities, allowing estimation of PA volume (in metabolic equivalents (MET)-min/week). Participants also reported the intensity of working PA and daily sitting time. Questionnaire data on diet, lifestyles and clinical variables including Helicobacter pylori serology were available. Adjusted odds ratios (OR) of GAC were estimated for domains of physical activity, stratifying by sex, site (cardia vs. non-cardia), and Lauren classification (intestinal vs. diffuse). RESULTS: Household physical activity (HPA) showed a strong inverse association with GAC, observed for both cardia and non-cardia tumours. Risk of overall gastric cancer was 50% lower risk among participants in the highest HPA category (OR = 0.50, 95%CI: 0.38, 0.66). Recreational physical activity (RPA) was also associated with lower overall GAC risk (OR = 0.68, 95% CI: 0.52, 0.88), particularly at moderate levels of intensity such as walking (OR = 0.61, 95% CI: 0.46, 0.79). The protective effect of RPA was strongest for non-cardia tumours. Sedentary time was not related to GAC risk (p-trend = 0.392), but the potential protective effect of RPA was restricted to non-sedentary participants. CONCLUSIONS: Both household and recreational physical activities were independently related to lower GAC risk in the MCC-Spain study.

Experience in real clinical practice with new direct acting antivirals in chronic hepatitis C. / Experiencia en práctica clínica real con los nuevos antivirales de acción directa en hepatitis crónica C.

INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. RESULTS: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available.

Accurate cut-offs for predicting endoscopic activity and mucosal healing in Crohn’s disease with fecal calprotectin

Background: Fecal biomarkers, especially fecal calprotectin, are useful for predicting endoscopic activity in Crohn’s disease; however, the cut-off point remains unclear. The aim of this paper was to analyze whether faecal calprotectin and M2 pyruvate kinase are good tools for generating highly accurate scores for the prediction of the state of endoscopic activity and mucosal healing. Methods: The simple endoscopic score for Crohn’s disease and the Crohn’s disease activity index was calculated for 71 patients diagnosed with Crohn’s. Fecal calprotectin and M2-PK were measured by the enzyme-linked immunosorbent assay test. Results: A fecal calprotectin cut-off concentration of ≥ 170 μg/g (sensitivity 77.6%, specificity 95.5% and likelihood ratio +17.06) predicts a high probability of endoscopic activity, and a fecal calprotectin cut-off of ≤ 71 μg/g (sensitivity 95.9%, specificity 52.3% and likelihood ratio -0.08) predicts a high probability of mucosal healing. Three clinical groups were identified according to the data obtained: endoscopic activity (calprotectin ≥ 170), mucosal healing (calprotectin ≤ 71) and uncertainty (71 > calprotectin < 170), with significant differences in endoscopic values (F = 26.407, p < 0.01). Clinical activity or remission modified the probabilities of presenting endoscopic activity (100% vs 89%) or mucosal healing (75% vs 87%) in the diagnostic scores generated. M2-PK was insufficiently accurate to determine scores. Conclusions: The highly accurate scores for fecal calprotectin provide a useful tool for interpreting the probabilities of presenting endoscopic activity or mucosal healing, and are valuable in the specific clinical context (AU)

No disponible

Accurate cut-offs for predicting endoscopic activity and mucosal healing in Crohn's disease with fecal calprotectin.

BACKGROUND: Fecal biomarkers, especially fecal calprotectin, are useful for predicting endoscopic activity in Crohn's disease; however, the cut-off point remains unclear. The aim of this paper was to analyze whether faecal calprotectin and M2 pyruvate kinase are good tools for generating highly accurate scores for the prediction of the state of endoscopic activity and mucosal healing. METHODS: The simple endoscopic score for Crohn's disease and the Crohn's disease activity index was calculated for 71 patients diagnosed with Crohn's. Fecal calprotectin and M2-PK were measured by the enzyme-linked immunosorbent assay test. RESULTS: A fecal calprotectin cut-off concentration of ≥ 170 µg/g (sensitivity 77.6%, specificity 95.5% and likelihood ratio +17.06) predicts a high probability of endoscopic activity, and a fecal calprotectin cut-off of ≤ 71 µg/g (sensitivity 95.9%, specificity 52.3% and likelihood ratio -0.08) predicts a high probability of mucosal healing. Three clinical groups were identified according to the data obtained: endoscopic activity (calprotectin ≥ 170), mucosal healing (calprotectin ≤ 71) and uncertainty (71 > calprotectin < 170), with significant differences in endoscopic values (F = 26.407, p < 0.01). Clinical activity or remission modified the probabilities of presenting endoscopic activity (100% vs 89%) or mucosal healing (75% vs 87%) in the diagnostic scores generated. M2-PK was insufficiently accurate to determine scores. CONCLUSIONS: The highly accurate scores for fecal calprotectin provide a useful tool for interpreting the probabilities of presenting endoscopic activity or mucosal healing, and are valuable in the specific clinical context.

Cinética lipídica en el tratamiento antiviral dual en pacientes con hepatitis crónica C / Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C

Fundamento y objetivo: Valorar el metabolismo basal y cinético de las lipoproteínas durante el primer mes de biterapia en pacientes con hepatitis crónica C genotipo 1 (HCC-1). Pacientes y métodos: Estudio longitudinal, prospectivo, que incluyó 99 pacientes HCC-1 naive, biopsiados y tratados con biterapia. Clasificamos a nuestros pacientes en 5 niveles de exigencia lipídica, según el grado de fibrosis hepática, carga viral basal y ratio de infectividad (cociente entre concentraciones medias de triglicéridos y colesterol unido a lipoproteínas de alta densidad durante el primer mes), estableciendo para cada uno de ellos, durante este período, una concentración media mínima necesaria de colesterol unido a lipoproteínas de baja densidad (colesterol LDL) para que el paciente alcanzara un «metabolismo lipídico favorable» (MLF), y valoramos su relación con las tasas de curación. Resultados: Alcanzaron mayores tasas de curación aquellos pacientes con fibrosis F3-F4 que presentaron mayores concentraciones basales de colesterol LDL, así como aquellos que consiguieron mantener durante el primer mes de biterapia una ratio de infectividad menor de 3,2 y mayores concentraciones medias de colesterol LDL: media (DE) de 100 (23) mg/dl en «curados» frente a 89 (28) mg/dl en «no curados»,odds ratio 1,1, intervalo de confianza del 95% (1,0-1,2) (p < 0,05), siendo más significativas estas diferencias en los genotipos IL-28B-CC (p = 0,013). Aquellos que alcanzaron la respuesta virológica sostenida presentaron mayores tasas de MLF. Conclusiones: No todos los pacientes con HCC-1 van a presentar durante el primer mes de tratamiento una cinética lipídica favorable, siendo necesario para curarse y/o alcanzar un MLF mantener durante este período unas concentraciones plasmáticas medias de colesterol LDL mayores. Aquellos con ausencia de un MLF podrían beneficiarse del uso de estatinas (AU)

Background and objective: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). Patients and methods: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different “degrees of lipid requirement” that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve 'a favorable lipid metabolism' (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. Results: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P < .05, these differences being more significant for genotype IL-28B-CC (P = .013). Patients with sustained virological response had higher rates of FLM. Conclusions: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins (AU)

[Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C]. / Cinética lipídica en el tratamiento antiviral dual en pacientes con hepatitis crónica C.

BACKGROUND AND OBJECTIVE: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). PATIENTS AND METHODS: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different "degrees of lipid requirement" that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve "a favorable lipid metabolism" (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. RESULTS: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P<.05, these differences being more significant for genotype IL-28B-CC (P=.013). Patients with sustained virological response had higher rates of FLM. CONCLUSIONS: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins.

Crohn's-like disease in a patient with common variable immunodeficiency treated with azathioprine and adalimumab.

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency. It is characterized by recurrent bacterial infections, and occurrence of autoimmune and neoplastic diseases is also frequent; there is also a high prevalence of gastrointestinal diseases. There are reports of inflammatory bowel disease in this entity, but incidence is low (2-4 %). We present the case of a patient with common variable immunodeficiency suffering a chronic diarrhea episode and who was diagnosed with ileocaecal Crohn s-like disease after performing intestinal transit, CT abdomen and colonoscopy with biopsy. It was first treated with prednisone but on showing cortisone dependency, treatment with azathioprine and adalimumab was started, with good results.

Enfermedad de Crohn-like en un paciente con inmunodeficiencia común variable tratada con azatioprina y adalimumab / Crohn’s-like disease in a patient with common variable immunodeficiency treated with azathioprine and adalimumab

La inmunodeficiencia común variable (IDCV) es la deficiencia primaria de anticuerpos más frecuente. Se caracteriza por infecciones bacterianas recurrentes, siendo también habitual la aparición de enfermedades autoinmunes y neoplásicas. Existe una alta prevalencia de enfermedades gastrointestinales. Se han descrito casos de enfermedad inflamatoria intestinal en esta entidad, pero con baja incidencia (2-4 %). Presentamos el caso de un paciente con inmunodeficiencia común variable que presenta un episodio de diarrea crónica, siendo diagnosticado de enfermedad de Crohn-like ileocecal tras realizar tránsito intestinal, TC de abdomen y colonoscopia con toma de biopsias. Se inició tratamiento con prednisona, pero presentó corticodependencia, por lo que se inicio tratamiento con azatioprina y adalimumab, presentando buena respuesta (AU)

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency. It is characterized by recurrent bacterial infections, and occurrence of autoimmune and neoplastic diseases is also frequent; there is also a high prevalence of gastrointestinal diseases. There are reports of inflammatory bowel disease in this entity, but incidence is low (2-4 %). We present the case of a patient with common variable immunodeficiency suffering a chronic diar - rhoea episode and who was diagnosed with ileocaecal Crohn s-like disease after performing intestinal transit, CT abdomen and colonoscopy with biopsy. It was first treated with prednisone but on showing cortisone dependency, treatment with azathioprine and adalimumab was started, with good results (AU)