Respuesta virológica sostenida en pacientes con hepatitis C crónica, tratados con antivirales de acción directa: un estudio retrospectivo en Costa Rica / Sustained virological response in patients with chronic hepatitis C treated with direct acting antivirals, a retrospective study from Costa Rica

Resumen Introducción: Costa Rica es un país con un sistema de salud pública que ha permitido detectar oportunamente a los pacientes con hepatitis C, y ofrecer un tratamiento con base en antivirales de acción directa (AAD) de última generación. No obstante, no se han publicado estudios que evalúen la respuesta de la población costarricense a estos fármacos. Objetivo: Describir la efectividad clínica del tratamiento con AAD en una cohorte tratada en la Caja Costarricense de Seguro Social (CCSS). Materiales y métodos: Estudio retrospectivo de los expedientes clínicos de los pacientes tratados con sofosbuvir / ledipasvir, sofosbuvir / velpatasvir y ombitasvir / paritaprevir / ritonavir / dasabuvir, en tres hospitales nacionales para adultos de la CCSS, en 2017 - 2018. Se recolectaron variables epidemiológicas, clínicas y analíticas, y se compararon los resultados pre y postintervención. Resultados: Se reclutaron 139 pacientes; 22 fueron excluidos porque no cumplían los criterios. El análisis se realizó con 117 pacientes, de los cuales 101 tenían viremia documentada para determinación de la respuesta virológica sostenida (RVS). La mayoría de los pacientes fue costarricense, nacida en 1945 - 1965, con factores de riesgo para hepatitis C no documentados, sin cirrosis e infectada por el genotipo 1b. La RVS general de la población estudiada fue del 98 %, sin notarse diferencia significativa entre pacientes cirróticos (94 %) y no cirróticos (100 %). Hubo una reducción significativa (p < 0,01) en: El índice de aspartato-aminotransferasa: número de plaquetas (APRI), el puntaje del Modelo para Enfermedad Hepática Terminal (MELD), la alaninoaminotransferase (ALT) y la bilirrubina total, para los pacientes tratados con AAD. Conclusión: Los antivirales de acción directa fueron efectivos en la población tratada en Costa Rica, con respuesta viral sostenida similar a aquella reportada en otros ensayos de vida real.

Abstract Introduction: Costa Rica has a public healthcare system that made possible the detection of hepatitis C (HCV) infected patients and offer them treatment with last-generation direct-acting antivirals (DAA). Nonetheless, there has not been any published studies that evaluate the response of the Costa Rican population to these drugs. Aim: To describe the clinical effectiveness of direct acting antiviral treatment in a cohort treated in the Social Security Care from Costa Rica (CCSS). Materials and Methods: Retrospective review of clinical records of all patients who were treated with: sofosbuvir/ledipasvir, sofosbuvir/velpatasvir and ombitasvir/paritaprevir/ritonavir/dasabuvir in three national adult hospitals from between 2017-2018. Epidemiological, clinical and laboratory data were collected, and pre- and post- treatment results were compared. Results: 139 patients were recruited, 22 were excluded because they did not fulfill the inclusión criteria. The analysis was made with 117 patients; from which 101 had their viremia documented in their records for the determination of sustained virological response (SVR). The majority of patients were Costa Ricans born between 1945-1965, whose risk factors for hepatitis C were not documented, with a non-cirrhotic, genotype 1b infection. Overall SVR was 98%. There was not a significant difference of response between cirrhotic (94%) and non-cirrhotic population (100%). There was a significant reduction (p< 0,01) in: Aspartate Aminotranferase to Platelet Ratio Index (APRI), the score of the Model for End-Stage Liver Disease (MELD), Alanine Aminotransferase (ALT) and total bilirubin in patients treated with DAA. Conclusion: The direct acting antivirals were effective in population treated in our country, with SVR similar to those reported in real life studies from other regions of the world.

Wilson disease in Costa Rica: Pediatric phenotype and genotype characterization.

INTRODUCTION: The prevalence of Wilson disease (WD) in Costa Rica is among the highest reported in the world, 4.9:100 000. Previous investigators have also described a burden of autosomal recessive conditions in this country. Genetic testing for WD began in 2010 as a strategy for earlier detection due to the country's high prevalence. Here we describe what we have learned about the genotype and phenotype of the Costa Rican pediatric population with WD. METHODS: We completed a retrospective review of medical records from pediatric individuals (<18 years of age) with molecular testing for ATP7B between 2010 and 2015. We documented phenotype and genotype for cases with WD as defined by the international scoring system. RESULTS: Thirty-four WD cases from 28 families were included, 15 female and 19 male patients. The most frequent pathogenic variant in ATP7B was NM_000053:c.3809A>G, p.Asn1270Ser, with 58.8% of affected individuals homozygous for this variant. Age of diagnosis ranged from 1 to 17 years, with an average of 8.8 ± 3.6 years. All individuals who presented with acute liver failure (n = 6) were homozygous for the p.Asn1270Ser variant (Chi-squared, P < .05). DISCUSSION: Molecular testing has facilitated the detection of presymptomatic patients with WD in Costa Rica. We hope that ongoing efforts in the delivery of clinical services lead to optimized molecular screening for WD and other genetic conditions in Costa Rica.

[ALFA-1 antitrypsin deficiency, a commonly missed cause of chronic liver disease in theadult: presentation of 9 cases with review of current literature]. / Déficit de Alfa-1 antitripsina, una causa de hepatopatía crónica comúnmente insospechada en el adulto: presentación de 9 casos con revisión de literature.

INTRODUCTION: Alfa 1-antitrypsin deficiency is one of the most prevalent genetic diseases in the human being, sadly it is not a commonly suspected clinical entity. With more than 100 known mutations, those associated with hepatic disease are the Z homocygote allele mutations in the gene a1AT which occur in every 2000-3500 births. Opposing to the pulmonary disease, in which de sequelae are caused by the deficit of this protein which in turn fastens the enzymatic destruction of the airway microstructure, the hepatic compromise is secondary to the intracellular accumulation of the aberrant misfolded protein. This accumulation causes cellular damage, hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma through activation of a series of mechanisms which culminate in hepatocitary apoptosis, regeneration and chronic cellular injury. MATERIALS AND METHODS: 9 cases of confirmed a1AT deficiency are presented, from different ages ranging from adolescence through elderly patients. RESULTS: Each of one of them with different clinical presentation going from asymptomatic liver enzyme elevations to transplanted cirrhosis in which the diagnosis was post procedural. CONCLUSION: We comment about the management of the chronic liver disease and the evolution of these patients through time in the liver clinic.

Déficit de Alfa-1 antitripsina, una causa de hepatopatía crónica comúnmente insospechada en el adulto: presentación de 9 casos con revisión de literatura / ALFA-1 antitrypsin deficiency, a commonly missed cause of chronic liver disease in the adult: presentation of 9 cases with review of current literature

Introducción: El déficit de alfa-1 Antitripsina (a1AT) es una de las enfermedades genéticas más prevalentes en el ser humano, lastimosamente como entidad clínica tiende a ser pobremente sospechada. Con más de 100 mutaciones conocidas, las que se encuentran asociadas a enfermedad hepática son los homocigotos Z en el alelo del gen a1AT que ocurre en 1 a 2000- 3500 nacimientos. A diferencia de la enfermedad pulmonar donde las secuelas ocurren primordialmente por el déficit propio de la a1AT con destrucción enzimática de la microestructura de la vía aérea, el compromiso hepático ocurre por acúmulo intracelular de la proteína Z mutante, que se desdobla de forma aberrante, en vez de ser secretada. Esta acumulación produce lesión celular, hepatitis, fibrosis, cirrosis y carcinoma hepatocelular (CHC) por desencadenar una serie de eventos que culminan con la apoptosis hepatocitaria, regeneración e injuria crónica. Materiales y métodos: Se presentan 9 casos de pacientes que se han encontrado bajo nuestro cuidado, con edades variadas desde infantes hasta adultos mayores. Resultados: Cada uno con una presentación clínica distinta que va desde la elevación de enzimas hepáticas y otros como cirrosis que se han trasplantado con diagnóstico confirmatorio postquirúrgico. Conclusión: Se comenta acerca del manejo de la hepatopatía y su progresión a lo largo del tiempo que se han mantenido en la clínica de hígado a nuestro cargo.

Introduction: Alfa 1-antitrypsin deficiency is one of the most prevalent genetic diseases in the human being, sadly it is not a commonly suspected clinical entity. With more than 100 known mutations, those associated with hepatic disease are the Z homocygote allele mutations in the gene a1AT which occur in every 2000-3500 births. Opposing to the pulmonary disease, in which de sequelae are caused by the deficit of this protein which in turn fastens the enzymatic destruction of the airway microstructure, the hepatic compromise is secondary to the intracellular accumulation of the aberrant misfolded protein. This accumulation causes cellular damage, hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma through activation of a series of mechanisms which culminate in hepatocitary apoptosis, regeneration and chronic cellular injury. Materials and methods: 9 cases of confirmed a1AT deficiency are presented, from different ages ranging from adolescence through elderly patients. Results: Each of one of them with different clinical presentation going from asymptomatic liver enzyme elevations to transplanted cirrhosis in which the diagnosis was post procedural. Conclusion: We comment about the management of the chronic liver disease and the evolution of these patients through time in the liver clinic.

Wilson's disease: A review of what we have learned.

Wilson's disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.

Adefovir Dipivoxil / Adefovir Dipivoxil

El adefovir es un nucleótido que se utiliza por vía oral, sin resistencia conocida hasta los dos años de tratamiento. Actúa en los pacientes con hepatitis B crónica Age+ y Age-, es efectivo en resistentes a lamivudina. Es un medicamento bien tolerado en cirróticos descompensados y trasplantados. Se requiere ajuste de dosis con alteración de la función renal.

Adefovir is a nucleotide orally administrated with unknown resistance until two years of treatment. It is recommended for patients with chronic hepatitis B + and e -, it is resistant to Lamivudine. It is a well tolerated drug by decompensated, transplanted cirrhotic. Dose adjustment is required in renal impairment.

Síndrome de Dubin Johnson / Dubin-Johnson`s Syndrome

Se presentan 5 pacientes con Síndrome de Dubin-Johnson diagnósticados entre noviembre de 1975 y noviembre de 1985 en el Hospital San Juan de Dios. Se realizó análisis clínico de laboratorio, gabinete y estudios histológicos del hígado. Tres de los 5 casos eran de sexo femenino, siendo los tres primeros casos presentados, hermanos. La edad en el momento del diagnóstico osciló entre 17 y 26 años siendo el promedio 20 años. Todos los casos cursaron con hiperbilirrubinemia de predominio directo, que no pasó de 4 mg/dl. Cuatro de los 5 casos, mostraron aumento paradójico en la eliminación de la bromosulftaleína (BSP); así mismo en los cuatro que se realizó biopsia hepática, ésta reveló depósito de pigmento pardo oscuro en los hepatocitos, descrito como característico de la enfermedad. El cuadro clínico se caracterizó principalmente por ictericia y hepatomegalia leve.

Hepatitis por halothano: un problema no resuelto / Halothane hepatitis: an unsolved problem

Se revisaron 48.969 anestesias con halothano suministradas en las salas de operaciones del Hospital San Juan de Dios entre los años 1976 a 1982, con el propósito de determinar la incidencia de hepatitis por halothano. De este número de anestesias suministradas, 6 pacientes presentan dicha entidad lo que indica 1 caso por cada 8.000 anestesias suministradas, con una mortalidad del 50% o sea 1 caso fatal por cada 16.000 anestesias administradas con halothano. La eosinofilia no se presentó. Los casos fatales están en relación con una segunda exposición al anestésico antes de un mes de la primera. El uso de esteroides en forma temprana puede ser um factor decisivo para la sobrevida