Changes in the epidemiology and distribution of the hepatitis C virus genotypes in North-Eastern Spain over the last 35 years / Cambios en la epidemiología y distribución de los genotipos del virus de la hepatitis C en el nordeste de España durante los últimos 35 años

Background: Genotypic distribution and epidemiology of HCV infection in Western Europe countries has changed over the last decades. Aim: To establish the local genotypic profile and characterize the associated demographic variables. Material and method: All the genotyping from 1988 to 2015 were considered. Associated demographic variables were included in logistic regression models. Genotyping was carried out with updated commercial kits. Results: Genotype 1b was the most prevalent (42.4%) followed by 1a (22.5%), 3 (18.6%), 4 (10.6%) and 2 (4.6%). The prevalence of 1a was higher in males, in patients younger than 45 and in intravenous drug users (IDU). 1b was more frequent in older than 45, with transfusion-associated and parenteral/nosocomial infections and in immigrants from Eastern Europe. Genotype 2 was highly prevalent in the postransfusional route (54.9%). Genotype 3 prevalence was high in males, in patients younger than 45, in IDU (69.3%) and in Asian and Eastern European immigrants. Genotype 4 was high in males, in patients younger than 45, and in IDU (63.5%). 1a, 3, 4 were the most prevalent genotypes in HIV-coinfected patients. There was a significant decline in genotype 1b and an increase in genotypes 3 and 4 over time. Conclusions: There has been a decline of genotype 1b, associated with transfusion or parenteral/nosocomial infections, and increases in the prevalence of genotypes 1a, 3 and 4 associated with male gender and IDU, now the most prevalent infection route. Immigration contributed with genotype 2 infections from Africa and genotype 1b and 3 infections from Eastern Europe and Asia (AU)

Antecedentes: La distribución genotípica y la epidemiología de la infección por el VHC en los países de Europa Occidental ha variado en las últimas décadas. Objetivo: Establecer el perfil genotípico local y distinguir las variables demográficas asociadas. Material y método: Se han tenido en cuenta todas las genotipificaciones desde 1988 a 2015. Las variables demográficas asociadas se incluyeron en modelos de regresión logística. La genotipificación se realizó con kits comerciales actualizados. Resultados: El genotipo 1b fue el más prevalente (42,4%), seguido por 1a (22,5%), 3 (18,6%), 4 (10,6%) y 2 (4,6%). La prevalencia de 1a fue mayor en varones, en pacientes menores de 45 años y en consumidores de drogas por vía intravenosa (CDVI). El genotipo 1b fue más frecuente en pacientes mayores de 45 años, con infecciones relacionadas con la transfusión y de tipo parenteral/nosocomial, y en inmigrantes de Europa Oriental. El genotipo 2 fue muy prevalente en la vía postransfusional (54,9%). La prevalencia del genotipo 3 fue elevada en varones, en pacientes menores de 45 años, en CDVI (69,3%) y en inmigrantes asiáticos y de Europa Oriental. El genotipo 4 fue elevado en varones, en pacientes menores de 45 años y en CDVI (63,5%). Los genotipos 1a, 3 y 4 fueron los más prevalentes en pacientes coinfectados con el VIH. Hubo una disminución considerable del genotipo 1b y un aumento en los genotipos 3 y 4 en el tiempo. Conclusiones: Se ha producido una disminución del genotipo 1b, relacionado con transfusiones o infecciones parenterales/nosocomiales, y un aumento en la prevalencia de los genotipos 1a, 3 y 4, relacionados con el sexo masculino y los CDVI, que actualmente son la vía de infección más prevalente. La inmigración contribuyó con infecciones del genotipo 2 de África e infecciones de los genotipos 1b y 3 de Europa Oriental y Asia (AU)

Changes in the epidemiology and distribution of the hepatitis C virus genotypes in North-Eastern Spain over the last 35 years.

BACKGROUND: Genotypic distribution and epidemiology of HCV infection in Western Europe countries has changed over the last decades. AIM: To establish the local genotypic profile and characterize the associated demographic variables. MATERIAL AND METHOD: All the genotyping from 1988 to 2015 were considered. Associated demographic variables were included in logistic regression models. Genotyping was carried out with updated commercial kits. RESULTS: Genotype 1b was the most prevalent (42.4%) followed by 1a (22.5%), 3 (18.6%), 4 (10.6%) and 2 (4.6%). The prevalence of 1a was higher in males, in patients younger than 45 and in intravenous drug users (IDU). 1b was more frequent in older than 45, with transfusion-associated and parenteral/nosocomial infections and in immigrants from Eastern Europe. Genotype 2 was highly prevalent in the postransfusional route (54.9%). Genotype 3 prevalence was high in males, in patients younger than 45, in IDU (69.3%) and in Asian and Eastern European immigrants. Genotype 4 was high in males, in patients younger than 45, and in IDU (63.5%). 1a, 3, 4 were the most prevalent genotypes in HIV-coinfected patients. There was a significant decline in genotype 1b and an increase in genotypes 3 and 4 over time. CONCLUSIONS: There has been a decline of genotype 1b, associated with transfusion or parenteral/nosocomial infections, and increases in the prevalence of genotypes 1a, 3 and 4 associated with male gender and IDU, now the most prevalent infection route. Immigration contributed with genotype 2 infections from Africa and genotype 1b and 3 infections from Eastern Europe and Asia.

Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection / Variables pronósticas de respuesta virológica sostenida tras la interrupción precoz del tratamiento triple con telaprevir de la infección por genotipo 1 del virus de la hepatitis C

BACKGROUND: Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients. AIM: To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR. MATERIAL AND METHOD: A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated. RESULTS: Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p < 0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p = 0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928. CONCLUSIONS: Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients

ANTECEDENTES: Los estudios de registro de telaprevir (TLV) y boceprevir (BOV) han mostrado tasas de interrupción precoz del tratamiento del 10-56%, pero no se ha comunicado la respuesta virológica sostenida (RVS) de estos pacientes. OBJETIVOS: Analizar la RVS, y los factores predictivos de esta, en una cohorte extensa de pacientes que pararon precozmente el tratamiento triple con TLV/BOV por causas diferentes a reglas de parada. MATERIAL Y MÉTODO: Se envió a 15 de hospitales de Cataluña un cuestionario relativo a los tratamientos con TLV/BOV finalizados antes del 31 de mayo de 2014, incluyendo información clínica, analítica, elastométrica y terapéutica de aquellos interrumpidos precozmente. Se realizaron análisis de regresión logística, curvas ROC y estimaciones pronósticas de las variables identificadas. RESULTADOS: Contestaron la encuesta 12 hospitales, sumando un total de 467 tratamientos con 121 (21,2%) interrupciones precoces del mismo, 76 (62,8%) por reglas de parada y 45 (37,2%) por otras causas. Hubo más paradas precoces en los tratamientos con BOV (38,2% [50/131] versus 21,1% [71/336]; p < 0,005), principalmente debidas a reglas de parada (78% [39/50] versus 52,1% [37/71]; p = 0,004). Alcanzaron RVS 21/121 pacientes (17,4%), 19/71 (26,8%) tratados con TLV y 2/50 (4,0%) tratados con BOV. En los pacientes que pararon el tratamiento por causas distintas a reglas de parada se alcanzó la RVS en 19/37 (55,9%) tratados con TLV y en 2/11 (18,2%) tratados con BOV. Los pacientes tratados con TLV que pararon el tratamiento por efecto adverso grave tuvieron una tasa de RVS del 61,5% (16/26). El análisis de regresión logística se hizo solo con los tratamientos triples con TLV parados precozmente. Las variables predictivas de RVS fueron el ARN-VHC indetectable en semana 4 y la duración del tratamiento mayor de 11 semanas. El mejor valor pronóstico (0,794) lo tuvo la duración total del tratamiento mayor de 11 semanas, con un VPP de 0,928. CONCLUSIONES: Los pacientes que paran precozmente el tratamiento triple con TLV por causas diferentes a reglas de parada conservan una tasa de RVS relevante (55,9%) en esta cohorte. El ARN-VHC indetectable en semana 4 y la duración del tratamiento mayor de 11 semanas son predictivas de RVS de este subgrupo de pacientes

Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection.

BACKGROUND: Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients. AIM: To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR. MATERIAL AND METHOD: A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated. RESULTS: Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p<0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928. CONCLUSIONS: Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.

La interrupción precoz del tratamiento triple con telaprevir de la hepatitis crónica C por efecto adverso grave no presupone necesariamente el fracaso del tratamiento / Early interruption of triple therapy with telaprevir in chronic hepatitis C due to severe adverse effects does not necessarily lead to treatment failure

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Considerar negativa una carga viral expresada como menor del límite inferior de cuantificación puede inducir a error en el diagnóstico y manejo terapéutico de la hepatitis C / To consider negative viral loads below the limit of quantification can lead to errors in the diagnosis and treatment of hepatitis C virus infection

Introducción Durante años ha sido habitual, con técnicas de RT-PCR para el ARN-VHC, expresar como menores del límite inferior de cuantificación (< LIC) tanto las cargas virales indetectables como las detectables < LIC. Ello podría causar error en el manejo de algunos pacientes. Objetivo Analizar la frecuencia e impacto clínico de considerar negativos los ARN-VHC detectables pero no cuantificables. Métodos Análisis retrospectivo de las determinaciones de ARN-VHC del período 2009-2011 (Cobas/Taqman, LIC: 15 UI/ml) diferenciando las cargas indetectables de las < LIC. Resultados Se analizaron 2.432 muestras de ARN-VHC en 1.371 pacientes encontrando 26 ARN < 15 (1,07%) en 23 pacientes (1,68%). Los ARN <15 predominaron en pacientes en tratamiento: 23 de 216 determinaciones de ARN-VHC (10,6%) y 20 de 88 pacientes (22,7%). El análisis del impacto clínico mostró: a) 2 pacientes informados de ARN-VHC < 15 tuvieron ARN cuantificables posteriormente; b) 8 de 9 pacientes (88,9%) con ARN < 15 solo en semana 4 de tratamiento alcanzaron RVS; c) los 3 pacientes con ARN < 15 en semana 12 y 48 semanas de tratamiento recidivaron; d) los 4 pacientes con ARN < 15 en semana 24 y/o posteriores fracasaron, y e) en 5 pacientes el impacto clínico fue nulo o no evaluable. Conclusiones El ARN < LIC indica viremia y asimilarlo a ARN-VHC negativo puede inducir a error en el manejo de la infección. Los ARN < LIC son especialmente prevalentes en pacientes en tratamiento. La edición de los resultados de la cuantificación del ARN-VHC debe ser clara, diferenciando la indetectabilidad de la positividad pero señalando esta cuando no sea cuantificable(AU)

Introduction For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions. Aim To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative. Material and method We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable» and those classified as «<1.50E + 01 IU/mL» (BLOQ). Results We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained. Conclusions This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ(AU)

[To consider negative viral loads below the limit of quantification can lead to errors in the diagnosis and treatment of hepatitis C virus infection]. / Considerar negativa una carga viral expresada como menor del límite inferior de cuantificación puede inducir a error en el diagnóstico y manejo terapéutico de la hepatitis C.

INTRODUCTION: For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions. AIM: To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative. MATERIAL AND METHOD: We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable¼ and those classified as «<1.50E+01IU/mL¼ (BLOQ). RESULTS: We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained. CONCLUSIONS: This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ.

Colecistostomía abierta o percutánea en pacientes de alto riesgo. Análisis de una serie de 30 pacientes / Open or percutaneous cholecystostomy in high-risk patients. Analysis of 30 patients

Introducción. La actitud ante la colecistitis aguda es la colecistectomía laparoscópica si es factible o, en su defecto, la colecistectomía abierta. En pacientes de avanzada edad, con importante comorbilidad y elevado riesgo anestésico, la colecistostomía es una opción terapéutica en la colecistitis aguda grave. Pacientes y método. Presentamos 30 casos tratados mediante colecistostomía en los últimos tres años. Todos los pacientes presentaron un cuadro de colecistitis aguda grave, con importante deterioro de su estado general y un alto riesgo anestésico por la avanzada edad y sus enfermedades asociadas. Resultados. La edad media de los pacientes (18 varones y 12 mujeres) fue de 79 años. En la analítica destacó la leucocitosis con o sin desviación a la izquierda en 28 casos (93 por ciento). El riesgo anestésico fue ASA IV en 25 casos (83 por ciento) y ASA III en los otros 5 (17 por ciento). En todos los casos se instauró tratamiento antibiótico intravenoso. La colecistostomía fue abierta en 12 pacientes y guiada por ecografía en 18. El germen más aislado fue Escherichia coli (16 pacientes, 53 por ciento). La morbilidad y la mortalidad de esta serie fueron del 57 y el 20 por ciento, respectivamente. Las curaciones llegaron al 80 por ciento de los casos. Conclusiones. En los pacientes ancianos y con importante afección de base, que supone un alto riesgo anestésico y quirúrgico en caso de colecistitis aguda grave, para conseguir un tratamiento curativo, se puede plantear la colecistostomía (radiológica o quirúrgica). (AU)

Divertículo epifrénico de grandes dimensiones: resolución mediante toracotomía y sutura mecánica / Giant epiphrenic diverticulum: resolution with thoracotomy and mechanical suture

Los divertículos epifrénicos, a pesar de ser infrecuentes y generalmente asintomáticos, pueden producir sintomatología clínica cuando son de gran tamaño. Se presenta el caso de un varón de 67 años, con molestias de varios años de evolución, que tras realizarle un tránsito baritado y una fibrogastroscopia se le diagnosticó un divertículo epifrénico de gran tamaño. Tras la cirugía el paciente está asintomático (AU)