Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal.

OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS: In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS: Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION: With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Tasas de colectomía en colitis ulcerosa 15 años después del diagnóstico. Datos de la cohorte Navarra 2001-2003 / Colectomy rate in ulcerative colitis 15 years after diagnosis: Results from the 2001-2003 Navarra cohort

Introducción: Conocer la historia natural de la colitis ulcerosa (CU) es esencial para entender la evolución de la enfermedad, evaluar el impacto de las distintas estrategias terapéuticas e identificar factores de mal pronóstico. Uno de los aspectos más relevantes, en este sentido, es la necesidad de cirugía.Objetivos: Analizar la tasa de incidencia de colectomía (TIC) desde el diagnóstico hasta el fin de seguimiento (31 de diciembre del 2017) e identificar factores predictivos de colectomía.Material y métodos: Estudio retrospectivo que incluye los pacientes con diagnóstico definitivo (DD) de CU o colitis inclasificable (CI) en la cohorte Navarra 2001 a 2003.Resultados: Incluimos 174 pacientes con DD de CU (E2 42,8% - E3 26,6%) y cinco de CI: 44,1% mujeres, mediana edad 39,2 años (rango siete a 88), mediana de seguimiento 15,7 años. Se intervienen ocho pacientes (TIC tres colectomías/103pac/a): tres al debut (< 1 mes), dos en los primeros dos años, dos a los cinco años y uno a los 12 años de evolución. Todos habían recibido esteroides, cinco inmunomoduladores y dos biológicos. En siete (87%) la cirugía fue urgente y la indicación, megacolon en tres (37,5%), brote grave en tres (37,5%) y fallo a tratamiento médico en dos (25%). En cinco casos (62,5%) se realizó un reservorio ileoanal y en tres una ileostomía definitiva. En el análisis univariante, los pacientes con pérdida > 5 kg e ingreso al debut presentaron una menor supervivencia libre de colectomía.Conclusiones: En nuestra serie, las tasas de colectomía son más bajas que las comunicadas habitualmente, mayoritariamente se realizan en los primeros cinco años de evolución y se indican con carácter urgente

Introduction: Knowing the natural history of ulcerative colitis (UC) is essential to understand the course of the disease, assess the impact of different treatment strategies and identify poor prognostic factors. One of the most significant matters in this regard is the need for surgery.Objectives: To analyse the Colectomy Incidence Rate (CIR) from diagnosis to end of follow-up (31/12/2017) and identify predictive factors for colectomy.Material and methods: A retrospective study enrolling patients with a definitive diagnosis (DD) of UC or Unclassified Colitis (UnC) in the 2001-03 Navarra cohort.Results: We enrolled 174 patients with a DD of UC (E2 42.8%; E3 26.6%) and 5 patients with a DD of UnC: 44.1% women, median age 39.2 years (range 7-88) and median follow-up 15.7 years. A total of 8 patients underwent surgery (CIR 3 colectomies/103 patient-years: 3 at initial diagnosis (<1 month), 2 in the first 2 years, 2 at 5 years from diagnosis and 1 at 12 years from diagnosis. All had previously received steroids; 5 had received immunomodulators and 2 had received biologics. In 7 patients (87%), surgery was performed on an emergency basis. The indication was megacolon in 3 (37.5%), severe flare-up in 3 (37.5%) and medical treatment failure in 2 (25%). In 5 cases (62.5%), an ileoanal pouch was made, and in 3 cases, a definitive ileostomy was performed. In the univariate analysis, patients with loss of more than 5 kg at diagnosis and admission at diagnosis had a lower rate of colectomy-free survival.Conclusions: In our series, colectomy rates are lower than usually reported. Most colectomies were performed in the first 5 years following diagnosis and had an emergency indication

Colectomy rate in ulcerative colitis 15 years after diagnosis: Results from the 2001-2003 Navarra cohort. / Tasas de colectomía en colitis ulcerosa 15 años después del diagnóstico. Datos de la cohorte Navarra 2001-2003.

INTRODUCTION: Knowing the natural history of ulcerative colitis (UC) is essential to understand the course of the disease, assess the impact of different treatment strategies and identify poor prognostic factors. One of the most significant matters in this regard is the need for surgery. OBJECTIVES: To analyse the Colectomy Incidence Rate (CIR) from diagnosis to end of follow-up (31/12/2017) and identify predictive factors for colectomy. MATERIAL AND METHODS: A retrospective study enrolling patients with a definitive diagnosis (DD) of UC or Unclassified Colitis (UnC) in the 2001-03 Navarra cohort. RESULTS: We enrolled 174 patients with a DD of UC (E2 42.8%; E3 26.6%) and 5 patients with a DD of UnC: 44.1% women, median age 39.2 years (range 7-88) and median follow-up 15.7 years. A total of 8 patients underwent surgery (CIR 3 colectomies/103 patient-years: 3 at initial diagnosis (<1 month), 2 in the first 2 years, 2 at 5 years from diagnosis and 1 at 12 years from diagnosis. All had previously received steroids; 5 had received immunomodulators and 2 had received biologics. In 7 patients (87%), surgery was performed on an emergency basis. The indication was megacolon in 3 (37.5%), severe flare-up in 3 (37.5%) and medical treatment failure in 2 (25%). In 5 cases (62.5%), an ileoanal pouch was made, and in 3 cases, a definitive ileostomy was performed. In the univariate analysis, patients with loss of more than 5 kg at diagnosis and admission at diagnosis had a lower rate of colectomy-free survival. CONCLUSIONS: In our series, colectomy rates are lower than usually reported. Most colectomies were performed in the first 5 years following diagnosis and had an emergency indication.

Recaptación de pacientes con antecedente de diagnóstico incompleto de infección por el virus de la hepatitis C / No disponible

ANTECEDENTES: desde la década de 1990 se realizan determinaciones de anticuerpos del virus de la hepatitis C (anti-VHC) y los resultados positivos no siempre fueron seguidos de determinación del ARN-VHC. Algunos de estos pacientes podrían tener una infección activa y no conocerlo. Se describe una intervención de captación activa de estos pacientes para completar el diagnóstico. MÉTODOS: se revisaron resultados históricos de laboratorio de Navarra y se identificaron pacientes con anti-VHC positivo que no se habían realizado ARN-VHC. En septiembre de 2018 se informó a cada médico de Atención Primaria de sus pacientes con instrucciones para completar el diagnóstico. Se ha evaluado esta actividad hasta diciembre de 2019. RESULTADOS: se detectaron 289 pacientes con anti-VHC positivo en los que no se había descartado infección activa. Dos tenían infección por VIH y seis habían fallecido. El contacto con los 281 restantes fue encargado a sus médicos de Primaria. A final de 2019, 187 (67 %) se habían realizado una nueva analítica, el 5 % decidió no analizarse, el 4 % vivía fuera de Navarra, el 3 % no se consiguió contactar y en el 2 % de los casos el médico no lo consideró procedente. El 19 % estaba pendiente de contactar. De 187 pacientes analizados, en 52 (28 %) se confirmó infección activa, el 40 % eran falsos positivos y el 31 % tenía ARN-VHC no detectable. De los 52 casos con infección activa, 34 ya habían iniciado tratamiento antiviral, tres ingresaron por cirrosis descompensada y uno falleció. CONCLUSIÓN: la recaptación de personas que habían quedado con un diagnóstico incompleto de infección por el VHC ha sido una estrategia eficiente de detección de infecciones activas para su tratamiento antiviral

No disponible

Recapture of patients with an incomplete diagnosis of hepatitis C virus infection.

BACKGROUND: hepatitis C virus (HCV) antibody tests have been performed since the 90s, although HCV-RNA (viral load) determination was not always performed. Some of these patients may be actively infected and not be aware of it. Here, we describe a procedure to capture these subjects and complete their diagnosis. METHODS: the historical laboratory results of Navarra were reviewed and individuals who were positive for antibodies against HCV (anti-HCV) and had not undergone HCV-RNA testing were identified. In September 2018, each general practitioner (GP) was informed about their patients and given precise instructions for completing the diagnosis. The procedure was assessed until December 2019. RESULTS: two hundred and eighty-nine anti-HCV positive patients were detected for whom active infection had not been discarded. Two were HIV-positive and six had already died. GPs were asked to assess the remaining 281 subjects. By the end of 2019, a new blood test had been performed in 187 (67 %) patients, 5 % decided not to do it, 4 % were living outside of Navarra, 3 % could not be contacted and the GP considered that it was not justified in 2 % of cases. Thus, 19 % remained to be contacted. From the 187 assessed patients, active infection was confirmed in 52 (28 %) individuals, 40 % were false positives and HCV-RNA was undetectable in 31 %. Regarding the 52 actively infected subjects, 34 had already initiated antiviral therapy and three were hospitalized due to decompensated cirrhosis, from which one patient died. CONCLUSIONS: the strategy to recapture individuals with an incomplete HCV infection diagnosis was effective to detect active infections and subsequent initiation of antiviral therapy.

Modification of liver fibrosis, glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents / Cambios en la fibrosis hepática, glucosa y perfil lipídico tras la eliminación del virus de la hepatitis C con antivirales de acción directa

INTRODUCTION: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels. METHODS: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48). RESULTS: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3) kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p < 0.001). DISCUSSION: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48

INTRODUCCIÓN: Se desconoce el efecto a largo plazo de los antivirales de acción directa (AAD) sobre la fibrosis hepática y el perfil metabólico en pacientes con hepatitis crónica C (HCC). Nuestro objetivo fue evaluar el impacto de la respuesta viral sostenida (RVS) sobre la rigidez hepática, la glucosa y el perfil lipídico. MÉTODOS: Un total de 445 pacientes con HCC monoinfectados iniciaron tratamiento con AAD libres de IFN entre enero del 2015 y febrero del 2017. La ET, los marcadores serológicos de fibrosis, los niveles de glucosa y lípidos se analizaron basalmente y 48 semanas tras finalizar el tratamiento (RVS48). RESULTADOS: La tasa de RVS fue del 97,7%. Finalmente analizamos 369 pacientes que obtuvieron RVS y tenían medidas fiables en la ET. La mediana de la rigidez hepática descendió de forma significativa de 9,3 (IQR 7,3-14,3) basalmente a 6,4 (IQR 4,9-8,9) kPa en RVS48 (p < 0,0001). El 54,7% de la cohorte presentó una regresión de la fibrosis. La mediana del FIB4 disminuyó de 2,0 (IQR 1,1-3,3) a 1,3 (IQR 0,9-2,0) (p < 0,0001). Las medianas del APRI y del Forns descendieron significativamente de 0,9 (IQR 0,5-1,7) a 0,3 (IQR 0,2-0,4) y de 6,2 (IQR 5,0-7,5) a 4,9 (3,8-5,9) (p < 0,001), respectivamente. La media de los niveles de colesterol total (CT) y LDL-C aumentaron de 172mg/dL y 101,5mg/dL a 191mg/dL y 117,5mg/dL (p < 0,0001), respectivamente. En el subgrupo de pacientes con prediabetes o diabetes, los niveles de glucosa descendieron de 142,7mg/dL a 127,2mg/dL en RVS48 (p < 0,001). DISCUSIÓN: La RVS reduce la rigidez hepática determinada mediante ET y marcadores serológicos de fibrosis en pacientes tratados con AAD. Nuestros resultados muestran una elevación en el CT y LDL-C y un descenso en los niveles de glucosa en RVS48

Modification of liver fibrosis, glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents.

INTRODUCTION: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels. METHODS: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48). RESULTS: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3)kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p<0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p<0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p<0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p<0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p<0.001). DISCUSSION: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.

Real-world evidence of the effectiveness of ombitasvir-paritaprevir/r ± dasabuvir ± ribavirin in patients monoinfected with chronic hepatitis C or coinfected with human immunodeficiency virus-1 in Spain.

AIM: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. MATERIAL AND METHODS: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. RESULTS: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. CONCLUSIONS: Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV.

Long-term changes on health-related quality of life in patients with chronic hepatitis C after viral clearance with direct-acting antiviral agents

Background and aim: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up. Methods: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL. Results: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05). Conclusions: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs

No disponible

Long-term changes on health-related quality of life in patients with chronic hepatitis C after viral clearance with direct-acting antiviral agents.

BACKGROUND AND AIM: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up. METHODS: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL. RESULTS: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05). CONCLUSIONS: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs.

Progress in the elimination of hepatitis C virus infection: A population-based cohort study in Spain.

BACKGROUND: The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficulties in the elimination of HCV infection in Navarra, Spain. METHODS: Using electronic healthcare databases, we performed a population-based prospective cohort study to describe changes in the prevalence of diagnosed active HCV infection at the beginning of 2015 and the end of 2017, the rate of new diagnoses and the rate of post-treatment viral clearance (PTVC) during this period. RESULTS: At the beginning of 2015 there were 1503 patients diagnosed with positive HCV-RNA, 2.4 per 1000 inhabitants, and at the end of 2017 the prevalence had decreased by 47%. In the study period, 333 (18 per 100,000 person-years) new positive HCV-RNA cases were detected, but only 76 (23%; 4.2 per 100,000 person-years) did not have anti-HCV antibodies previously detected. Prevalent cases and new diagnoses of active infection were more frequent in men, people born in 1950-1979, HIV-infected patients and in those with lower income levels. Among patients with HCV-RNA, 984 achieved PTVC (22.7 per 100 person-years). PTVC was less frequent in patients born before 1940, in immigrants and in patients with lower income levels. CONCLUSIONS: The prevalence of diagnosed active HCV infection has dropped by almost half over three years, because the number of patients with PTVC was much higher than the number of new diagnoses. Interventions specifically targeted at population groups with less favourable trends may be necessary.

Safety of oral direct acting antiviral regimens for chronic hepatitis C in real life conditions.

OBJECTIVES: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions. METHODS: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA. RESULTS: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion. CONCLUSION: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.

Valor predictivo pretratamiento del cociente neutrófilos/linfocitos circulantes sobre la posibilidad de resección R0 en el cáncer gástrico / Pretreatment predictive value of blood neutrophil/lymphocyte ratio in R0 gastric cancer resectability

INTRODUCCIÓN: Se necesitan nuevos parámetros, complementarios al TNM clínico, para orientar preoperatoriamente acerca de la resecabilidad R0 del cáncer gástrico. Analizaremos el posible valor predictivo del cociente neutrófilos/linfocitos (N/L) circulantes sobre dicha resecabilidad. MÉTODOS: Estudiamos retrospectivamente 257 carcinomas gástricos, diagnosticados consecutivamente y sin tratamiento neoadyuvante. Realizamos un análisis univariante y multivariante de la frecuencia de casos con resección R0 entre los grupos con cociente N/L «normal» (< 5) y «patológico» (≥ 5). Adicionalmente, estudiamos el subgrupo de pacientes operados (n = < 5 o ≥ 5. RESULTADOS: Fueron operados 156 casos, con 139 resecciones R0. Registramos un cociente N/L elevado en 46 casos (17,9%). Globalmente, la resecabilidad R0 fue superior en los pacientes con cociente N/L < 5: 59,7% frente al cociente ≥ 5: 28,6% (p < 0,001; OR = 3,76; IC 95% = 1,78-8,04). En el análisis multivariante se confirma la relación entre cociente N/L < 5 y resección R0 (p = 0,006; OR = 3,86; IC 95% = 1,46-10,22). En el subgrupo de pacientes operados se mantiene la mayor frecuencia de resección R0 en los casos con cociente < 5: 91,3% frente a 72,2% (p = 0,015; OR = 4,04; IC 95% = 1,23-13,26). CONCLUSIONES: De modo global, un cociente N/L < 5 en el momento del diagnóstico del cáncer gástrico se relaciona de modo significativo e independiente con una mayor frecuencia de resección tumoral R0. En el subgrupo de pacientes operados se confirma esta mayor proporción de resección R0 en los casos con cociente N/L < 5

INTRODUCTION: New parameters complementary to clinical TNM classification are needed, to orient preoperative on the possibility of a R0 gastric cancer resection. We analysed the possible predictive value of blood neutrophil/lymphocytic ratio (N/L) in relation to resectability. METHODS: Two hundred and fifty-seven gastric cancers consecutively diagnosed and without neoadjuvant treatment were retrospectively studied. Univariate and multivariate analysis of the frequency of R0 cases was performed between groups with a normal N/L ratio (< 5) and pathological N/L ratio (≥ 5). Furthermore, we studied the subgroup of operated patients (n = 156) analysing the frequency of R0 resection according to N/L ratio < 5 or ≥ 5. RESULTS: One hundred and fifty-six patients underwent surgical intervention, of which 139 had R0 resections. A high N/L ratio was registered in 46 cases (17.9%). Globally, resectability was higher in patients with a N/L ratio < 5: 59.7% vs. N/L ratio ≥ 5: 28.6% (P < .001; OR = 3.76; 95% C = 1.78-8.04). The relation between N/L ratio < 5 and R0 resection was confirmed in the multivariate (P = .006; OR = 3.86; 95% CI = 1.46-10.22). In the operated subgroup, the higher frequency of R0 resection achievement is maintained in cases with N/L ratio < 5: 91.3% vs. 72.2% (P = .015; OR =4.04; 95% CI = 1.23-13.26). CONCLUSIONS: The presence of a N/L ratio < 5 at the diagnosis of a gastric carcinoma is related in a significant and independent way with a higher frequency of R0 tumoral resection, globally. This higher proportion of R0 resection cases in patients with a N/L < 5 ratio is confirmed in the subgroup of operated patients

Chronic Pancreatitis-Like Changes Detected by Endoscopic Ultrasound in Type 1 Diabetics Are Not Associated With Gastrointestinal Symptoms or Nutritional Deficiencies.

OBJECTIVES: Previous studies have shown changes in the pancreas of type 1 diabetic (T1-DM) patients, similar to those present in patients with chronic pancreatitis. Our aim was to analyze the prevalence of endoscopic ultrasound (EUS) criteria for chronic pancreatitis in T1-DM, to determine the association with factors related to the diabetes and to define its clinical significance. METHODS: Eighty-six T1-DM patients were prospectively included. All of them underwent EUS. Standard criteria were used. Patients were divided into 3 groups according to the number of EUS criteria they met: group A, 0 to 2 criteria; group B, 3 to 4; and group C, more than 4. Association between EUS findings and demographic or clinical factors was studied as well as the relationship between EUS abnormalities and the presence of gastrointestinal symptoms or nutritional deficiencies. RESULTS: Fifty-three patients (61.6%) showed at least 1 morphologic abnormality. Fifty-eight patients were included in group A, 21 in group B, and 7 in Group C. No significant differences were found when comparing the 3 groups. CONCLUSIONS: Chronic pancreatitis-like changes are frequent in the pancreas of T1-DM patients. These changes are not associated with demographic or clinical data. Therefore, the clinical relevance seems to be scarce.

Pretreatment predictive value of blood neutrophil/lymphocyte ratio in R0 gastric cancer resectability. / Valor predictivo pretratamiento del cociente neutrófilos/linfocitos circulantes sobre la posibilidad de resección R0 en el cáncer gástrico.

INTRODUCTION: New parameters complementary to clinical TNM classification are needed, to orient preoperative on the possibility of a R0 gastric cancer resection. We analysed the possible predictive value of blood neutrophil/lymphocytic ratio (N/L) in relation to resectability. METHODS: Two hundred and fifty-seven gastric cancers consecutively diagnosed and without neoadjuvant treatment were retrospectively studied. Univariate and multivariate analysis of the frequency of R0 cases was performed between groups with a normal N/L ratio (<5) and pathological N/L ratio (≥5). Furthermore, we studied the subgroup of operated patients (n=156) analysing the frequency of R0 resection according to N/L ratio<5 or≥5. RESULTS: One hundred and fifty-six patients underwent surgical intervention, of which 139 had R0 resections. A high N/L ratio was registered in 46 cases (17.9%). Globally, resectability was higher in patients with a N/L ratio<5: 59.7% vs. N/L ratio≥5: 28.6% (P<.001; OR=3.76; 95% CI=1.78-8.04). The relation between N/L ratio<5 and R0 resection was confirmed in the multivariate (P=.006; OR=3.86; 95% CI=1.46-10.22). In the operated subgroup, the higher frequency of R0 resection achievement is maintained in cases with N/L ratio<5: 91.3% vs. 72.2% (P=.015; OR=4.04; 95% CI=1.23-13.26). CONCLUSIONS: The presence of a N/L ratio<5 at the diagnosis of a gastric carcinoma is related in a significant and independent way with a higher frequency of R0 tumoral resection, globally. This higher proportion of R0 resection cases in patients with a N/L<5 ratio is confirmed in the subgroup of operated patients.

Valor pronóstico pretratamiento del antígeno carcinoembrionario en el cáncer colorrectal operado. ¿Es útil en todos los estadios del tumor? / Prognostic value of preoperative carcinoembryogenic antigen: Is it useful in all stages of colorectal cancer?

INTRODUCCIÓN: Publicaciones recientes han reactivado la discusión sobre el valor pronóstico de la elevación pretratamiento del antígeno carcinoembrionario (CEA) en el cáncer colorrectal. Debido a los resultados discordantes comunicados, pretendemos analizar en nuestro medio esta posible capacidad predictiva, globalmente y en los diferentes estadios tumorales. PACIENTES Y MÉTODOS: Estudiamos retrospectivamente 303 cánceres colorrectales resecados consecutivamente con intención curativa, analizando la mortalidad debida al tumor. Determinamos la frecuencia de casos con CEA pretratamiento patológico (>5 mg/l). Comparamos mediante análisis univariante y multivariante las curvas de supervivencia entre los casos con CEA normal y patológico, tanto en el global de la serie como en los diferentes estadios pTNM. RESULTADOS: La frecuencia de pacientes con CEA > 5 mg/l fue del 31%. La mediana de seguimiento clínico alcanzó los 83 meses. En el análisis multivariante de la serie global, la supervivencia fue desfavorable para los casos con CEA elevado: hazard ratio (HR) = 1,89; intervalo de confianza al 95% (IC 95%) = (1,15-3,10); p = 0,012. Al efectuar el análisis de supervivencia en los diversos estadios, únicamente se mantiene el valor predictivo en el estadio II (n = 104): HR = 3,02; IC 95% = (1,22-7,45); p = 0,017. CONCLUSIONES: Antes del inicio del tratamiento, un 31% de nuestros cánceres colorrectales resecados con intención curativa presentaron unos valores patológicos de CEA. Considerando la serie globalmente, la elevación del CEA pretratamiento presenta, de modo independiente, un valor pronóstico desfavorable sobre la supervivencia, pero al analizar su valor predictivo según los diferentes estadios, solo mantiene su significación en el estadio pTNM II

INTRODUCTION: Recent reports have reopened discussion of the prognostic value of elevated pre-treatment carcinoembryonic antigen (CEA) levels in colorectal cancer. Due to the discrepancies in the published results, we aimed to analyze the possible predictive value of CEA, both overall and in different tumoral stages in our environment. PATIENTS AND METHODS: We retrospectively studied 303 consecutive patients with colorectal cancer resected with curative intent by analysing tumor-related mortality. The frequency of patients with increased CEA levels (> 5 mg/l) was registered. Univariate and multivariate analyses of survival curves were performed, comparing patients with increased CEA levels and those with CEA levels within normal limits, both in the overall series and in the different pTNM tumoral stages. RESULTS: Frequency of patients with CEA > 5 mg/l was 31%. The median clinical follow-up was 83 months. A poor survival rate was registered in the multivariate analysis of the whole series in patients with high CEA levels: hazard ratio (HR) = 1.81; 95% confidence interval (95% CI) = (1.15-3.10); P=.012. This predictive value was only maintained in stage II in the survival analysis of the distinct tumoral stages (n = 104): HR = 3.02; 95% CI = (1.22-7.45); P=.017. CONCLUSIONS: Before treatment, 31% of our patients with colorectal cancer resected with curative intent had pathological CEA values. In the overall series, a high pretreatment CEA level showed an independent prognostic value for poor survival. When pTNM tumoral stages were analyzed separately, CEA level had predictive value only in pTNM II tumors

[Prognostic value of preoperative carcinoembryogenic antigen: Is it useful in all stages of colorectal cancer?]. / Valor pronóstico pretratamiento del antígeno carcinoembrionario en el cáncer colorrectal operado. ¿Es útil en todos los estadios del tumor?

INTRODUCTION: Recent reports have reopened discussion of the prognostic value of elevated pre-treatment carcinoembryonic antigen (CEA) levels in colorectal cancer. Due to the discrepancies in the published results, we aimed to analyze the possible predictive value of CEA, both overall and in different tumoral stages in our environment. PATIENTS AND METHODS: We retrospectively studied 303 consecutive patients with colorectal cancer resected with curative intent by analysing tumor-related mortality. The frequency of patients with increased CEA levels (> 5mg/l) was registered. Univariate and multivariate analyses of survival curves were performed, comparing patients with increased CEA levels and those with CEA levels within normal limits, both in the overall series and in the different pTNM tumoral stages. RESULTS: Frequency of patients with CEA>5mg/l was 31%. The median clinical follow-up was 83 months. A poor survival rate was registered in the multivariate analysis of the whole series in patients with high CEA levels: hazard ratio (HR)=1.81; 95% confidence interval (95% CI)=(1.15-3.10); P=.012. This predictive value was only maintained in stage II in the survival analysis of the distinct tumoral stages (n=104): HR=3.02; 95% CI=(1.22-7.45); P=.017. CONCLUSIONS: Before treatment, 31% of our patients with colorectal cancer resected with curative intent had pathological CEA values. In the overall series, a high pretreatment CEA level showed an independent prognostic value for poor survival. When pTNM tumoral stages were analyzed separately, CEA level had predictive value only in pTNM II tumors.

Lesiones gastrointestinales y características de las hemorragias digestivas agudas en los pacientes anticoagulados con acenocumarol / Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients

En los últimos años ha aumentado el número de pacientes anticoagulados y en consecuencia las complicaciones hemorrágicas derivadas de este tratamiento. Analizamos las hemorragias digestivas (HD) por ser las más frecuentes entre las hemorragias mayores y planteamos que estos sujetos deben presentar lesiones responsables de la HD independientemente de la intensidad de la anticoagulación, si bien aquellos excesivamente anticoagulados presentarán hemorragias más graves.ObjetivosEstudiar las características de los pacientes anticoagulados con HD y la relación entre el grado de anticoagulación con el hallazgo de lesiones responsables y la gravedad de la hemorragia.Pacientes y métodosEstudiamos prospectivamente 96 pacientes con HD, anticoagulados con acenocumarol, ingresados consecutivamente entre el 1 de enero de 2003 y el 30 de septiembre de 2005. Se excluyeron aquellos con hepatopatía severa y 9 por faltar datos.ResultadosLa incidencia de HD fue de 19,6 casos/100.000 habitantes-año. El 90% de los de los pacientes presentaron lesiones responsables (85% de las HDA y 50% de las HDB) o potencialmente responsables del sangrado y el 30% requirió tratamiento endoscópico de dichas lesiones sin observarse diferencias en función del grado de anticoagulación. Tampoco se encontraron diferencias en el tipo de lesiones, si bien los pacientes excesivamente anticoagulados presentaron hemorragias más graves (un 23% de aquellos con un IRN ≥ 4 tuvieron hemorragias con compromiso vital frente a un 4% de los pacientes con un INR < 4). Conclusiones: Observamos una incidencia 20 HD graves en anticoagulados/100.000 habitantes-año, sin diferencias ni en el tipo, ni en la frecuencia de lesiones responsables en función del grado de anticoagulación. Los pacientes excesivamente anticoagulados presentan HD más graves

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. Objectives: To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. Patients and methods: We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. Results: The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic . No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥ 4 had a life-threatening bleed versus only 4% of patients with INR < 4). Conclusions: We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes

Valor predictivo de la hipoalbuminemia pre-tratamiento sobre el pronóstico del cáncer colorrectal resecado / Predictive value of pre-treatment hypoalbuminemia in prognosis of resected colorectal cancer

INTRODUCCIÓN: La albúmina forma parte de la respuesta sistémica inflamatoria antitumoral, por lo que analizaremos su valor en el pronóstico pre-operatorio del carcinoma colorrectal (CCR).Pacientes y métodos Estudio retrospectivo y observacional de una serie de CCR resecados consecutiva y programadamente. Efectuamos un análisis estadístico univariante y multivariante de la supervivencia entre los casos con y sin hipoalbuminemia pretratamiento (< 3,5 g/dl), globalmente y en el subgrupo en estadio pTNM II . Adicionalmente, comparamos el índice de mortalidad debida al tumor a los 5 años entre los casos con y sin hipoalbuminemia. Resultados Revisamos 207 pacientes (mediana de seguimiento: 81 meses). En el análisis multivariante global los casos con normoalbuminemia presentaron unas curvas de supervivencia superiores a las de los pacientes con hipoalbuminemia: (HR = 2,82; IC 95% = [1,54-5,19]; p = 0,001). Este mejor pronóstico de la normoalbuminemia se mantiene en el estadio pTNM II: (HR = 3,76; IC 95% = [1,40-10,08]; p = 0,009). El índice de mortalidad a los 5 años fue inferior en los casos con normoalbuminemia: global=18,8 versus 42,9% (OR = 3,24; IC 95% = [1,48-7,12]; p = 0,001); estadio pTNM II=13,3 versus 44,4% (OR = 5,2; IC 95% = [1,36-20,34]; p = 0,004). CONCLUSIÓN: Una hipoalbuminemia pre-tratamiento < 3,5g/dl se relaciona, de modo independiente, con una menor supervivencia tras la resección, tanto globalmente como en los CCR en estadio pTNM II. De confirmarse estos resultados la hipoalbuminemia constituiría un sencillo y significativo marcador de mal pronóstico, disponible desde el momento del diagnóstico

INTRODUCTION: Albuminemia is part of the antitumoral systemic inflammatory response. We therefore analyzed its possible value in establishing the preoperative prognosis of colorectal carcinoma (CRC). PATIENTS AND METHODS: We conducted a retrospective, observational study of a series of consecutive patients who underwent CRC resection. Univariate and multivariate analyses of survival curves were performed in patients with and without pre-treatment hypoalbuminemia (< 3.5 g/dl), both in the overall group of patients and in the subgroup of those with pTNM stage II tumors. In addition, we compared the 5-year tumor-related mortality in patients with and without hypoalbuminemia. RESULTS: A total of 207 patients were reviewed (median follow-up: 81 months). In the overall multivariate analysis, survival curves were better in patients with normal albumin levels than in those with hypoalbuminemia (HR = 2.82; CI 95% = [1.54-5.19]; P = .001). This better prognostic value of normal albumin levels was also significant in pTNM stage II tumors: (HR = 3.76; CI 95% = [1.40-10.08]; P = .009). The 5-year mortality index was lower in patients with normal albumin levels: overall series = 18.8% vs 42.9% (OR =3.24; CI 95% = [1.48-7.12]; p = 0.001); pTNM stage ii=13.3% vs 44.4% (OR = 5.2; CI 95% = [1.36-20.34]; P = 0.004). CONCLUSIONS: Pre-treatment hypoalbuminemia (< 3.5 g/dl) was independently related to shorter survival after tumor resection, both in the overall series of patients and in pTNM stage II CRC. If these results are confirmed, hypoalbuminemia would be a simple and significant marker of poor prognosis, available at the initial diagnosis