Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure.

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of "extra-target" RAS suggests the need for RAS screening in all three DAA target regions.

Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado / Vascular diseases of the liver. Clinical Guidelines from the Catalan Society of Digestology and the Spanish Association for the Study of the Liver

Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía (AU)

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide (AU)

Reactivación del virus de la hepatitis B tras el cese de la profilaxis con entecavir en un paciente con leucemia linfoblástica tipo Burkitt tratado con rituximab / Hepatitis B virus reactivation after cessation of prophylaxis with entecavir in a patient with Burkitt type acute lymphoblastic leukaemia treated with rituximab

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Vascular diseases of the liver. Clinical Guidelines from the Catalan Society of Digestology and the Spanish Association for the Study of the Liver. / Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado.

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.

Factores pronósticos asociados a la mortalidad de los pacientes con hepatitis alcohólica grave / Prognostic factors associated with mortality in patients with severe alcoholic hepatitis

La hepatitis alcohólica grave se asocia a una mortalidad precoz elevada. El objetivo de nuestro estudio fue identificar los factores pronósticos asociados a la mortalidad intrahospitalaria, la mortalidad a medio y a largo plazo de la hepatitis alcohólica grave, así como evaluar los diferentes índices pronósticos en una cohorte de pacientes de nuestro hospital. Realizamos un análisis de 66 episodios consecutivos que ingresaron durante el periodo 2000-2008. Se recogieron y analizaron los datos clínicos y analíticos al ingreso, a la semana, al mes, a los 6 meses y al año, así como datos sobre el tratamiento recibido y las complicaciones asociadas durante el ingreso. Se calcularon y evaluaron los diferentes índices pronósticos de la literatura. La mortalidad asociada a un episodio de hepatitis alcohólica grave se produjo sobre todo durante el primer mes, con una tasa media de mortalidad del 16,9 %. Las complicaciones infecciosas se relacionaron con una menor supervivencia intrahospitalaria. Los valores de MELD, urea y bilirrubina a los 7 días de ingreso fueron los únicos factores independientes de supervivencia intrahospitalaria (OR = 1,14; 1,012 y 1,1, respectivamente) y a los 6 meses (OR = 1,15; 1,014 y 1,016, respectivamente). A los 12 meses, solo los valores de MELD y urea a los 7 días fueron factores independientes de supervivencia. En nuestra cohorte el MELD fue el mejor índice pronóstico para predecir la mortalidad asociada a un episodio de hepatitis alcohólica grave (AU)

Severe alcoholic hepatitis is associated with high early mortality. This study aimed at identifying prognostic factors associated with in-hospital, medium- and long-term mortality of severe alcoholic hepatitis and to evaluate the different prognostic scoring systems on a cohort of patients in our hospital. To this end, we conducted a retrospective analysis of 66 episodes admitted between 2000 and 2008. Clinical and laboratory data on admission, at 7 days, 1 month, 6 months, and after one year were collected and analyzed, as were the details on the treatment and complications that occurred during hospitalization; the different prognostic indices used in the literature were calculated. Death event associated with an episode of severe alcoholic hepatitis occurs primarily during the first month, with an average mortality rate of 16.9. Infectious complications were associated with lower in-hospital survival. MELD score, urea and bilirubin values one week after admission were independently associated with both in-hospital survival (OR = 1.14, 1.012 and 1.1, respectively), and survival at 6 months (OR = 1, 15; 1.014 and 1.016, respectively). Only MELD score and urea values at 7 days were independent predictors of survival twelve months after the acute hepatitis episode. MELD score, urea, and bilirubin 7 days after admission were the only independent in-hospital survival and also long-term survival factors 6 months and one year after the episode. In our cohort, the MELD score was the best prognostic index to predict mortality associated with an episode of severe alcoholic hepatitis (AU)

[Prognostic factors associated with mortality in patients with severe alcoholic hepatitis]. / Factores pronósticos asociados a la mortalidad de los pacientes con hepatitis alcohólica grave.

Severe alcoholic hepatitis is associated with high early mortality. This study aimed at identifying prognostic factors associated with in-hospital, medium- and long-term mortality of severe alcoholic hepatitis and to evaluate the different prognostic scoring systems on a cohort of patients in our hospital. To this end, we conducted a retrospective analysis of 66 episodes admitted between 2000 and 2008. Clinical and laboratory data on admission, at 7 days, 1 month, 6 months, and after one year were collected and analyzed, as were the details on the treatment and complications that occurred during hospitalization; the different prognostic indices used in the literature were calculated. Death event associated with an episode of severe alcoholic hepatitis occurs primarily during the first month, with an average mortality rate of 16.9. Infectious complications were associated with lower in-hospital survival. MELD score, urea and bilirubin values one week after admission were independently associated with both in-hospital survival (OR = 1.14, 1.012 and 1.1, respectively), and survival at 6 months (OR = 1, 15; 1.014 and 1.016, respectively). Only MELD score and urea values at 7 days were independent predictors of survival twelve months after the acute hepatitis episode. MELD score, urea, and bilirubin 7 days after admission were the only independent in-hospital survival and also long-term survival factors 6 months and one year after the episode. In our cohort, the MELD score was the best prognostic index to predict mortality associated with an episode of severe alcoholic hepatitis.