Risk factors for developing hepatocellular carcinoma in patients treated with direct-acting antivirals.

INTRODUCTION AND AIM: Chronic hepatitis C is one of the main causes of cirrhosis of the liver. Treatment with direct-acting antivirals (DAAs) improves survival. There is controversy as to whether AADs create an increased risk for the development of hepatocellular carcinoma (HCC). The aim of the present study was to determine the risk factors for developing HCC in patients with chronic hepatitis C treated with DAAs. MATERIALS AND METHODS: A cohort study was conducted, within the time frame of June 2017 and June 2018, on patients >18 years of age, with chronic hepatitis C, genotypes 1 and 4, with one year of follow-up, to evaluate the presence of HCC. RESULTS: We analyzed 108 patients, 71 (65%) of whom were women. Mean patient age was 56.24 years (±10.6), 1b was the most frequent genotype (63%), and 49% of the patients received treatment with DAAs (ombitasvir/paritaprevir/ritonavir plus dasabuvir). Thirty-four (31%) patients were obese. Fifty-three percent (58) had cirrhosis and 82% (89) had Child-Pugh class A liver function. Sustained virologic response at 12 weeks was 100%. Eight (7%) patients developed HCC and 1b was the most frequently associated genotype (87%). The presence of regenerative nodules >10 mm (P < .05), esophageal varices (P < .05), cirrhosis of the liver (P < .05), Child-Pugh B-C (P < .05), and alpha-fetoprotein >20 IU/mL (P = 0.20) one year after treatment were associated with the development of HCC. CONCLUSIONS: The risk factors for developing HCC were the presence of cirrhosis of the liver, Child-Pugh class B liver function, esophageal and/or gastric varices, and genotype 1b.

Primer reporte en Perú sobre terapia con antivirales de acción directa para hepatitis C crónica en pacientes VIH-positivos / First report in Peru on direct-acting antiviral therapy for chronic hepatitis C in HIV-positive patients

RESUMEN Objetivo : Presentar la experiencia clínica con antivirales de acción directa (AAD) para hepatitis C crónica en pacientes VIHpositivos. Materiales y métodos : Serie de casos longitudinal y prospectiva de pacientes VIH-positivos tratados con AAD para hepatitis C crónica entre mayo de 2019 y abril de 2020 en el Servicio de Infectología del Hospital Nacional Guillermo Almenara Irigoyen, EsSalud. El desenlace primario fue la respuesta viral sostenida del virus de hepatitis C (VHC) a las 12 semanas de completada la terapia con AAD. Los desenlaces secundarios fueron tolerabilidad y seguridad. Resultados : Diez pacientes fueron incluidos en el estudio, dos fueron mujeres (20%). Dos pacientes presentaron cirrosis (20%). La totalidad de los pacientes tuvo la carga viral del VIH suprimida antes de la terapia con AAD. Los pacientes recibieron un esquema de 12 semanas con base en sofosbuvir: uno con daclatasvir por separado, y los nueve restantes con velpatasvir combinados en una sola tableta por día. La respuesta viral sostenida del VHC fue evaluable en nueve casos. En estos, la carga viral del VHC fue no detectable. No se registraron ocurrencias en cuanto a tolerabilidad y seguridad durante la terapia con los AAD indicados. Conclusiones : La presente investigación es la primera experiencia clínica en Perú con AAD para hepatitis C crónica en pacientes VIH-positivos. La respuesta virológica, la tolerabilidad y la seguridad frente a daclatasvir y velpatasvir, cada uno junto o combinado con sofosbuvir, fueron óptimas en la serie de casos presentada.

ABSTRACT Objective : To present the clinical experience with direct-acting antivirals (DAAs) for chronic hepatitis C in HIV-positive patients. Materials and methods : Longitudinal and prospective case series of HIV-positive patients treated with DAAs for chronic hepatitis C between May 2019 and April 2020 at the Infectious Diseases Service of Hospital G. Almenara, EsSalud. The primary outcome was sustained virologic response to hepatitis C virus (HCV) 12 weeks after completion of DAA therapy. Secondary outcomes were tolerability and safety. Results : Ten patients were included in the study, two were women (20%). Two patients had cirrhosis (20%). All patients had suppressed HIV viral load prior to DAA therapy. Patients received a 12-week regimen based on sofosbuvir: one with daclatasvir separately, and the remaining nine with velpatasvir combined in a single tablet per day. The sustained virological response of HCV was evaluable nine cases. In these, the HCV viral load was undetectable. No occurrences were recorded regarding tolerability and safety during therapy with the indicated DAAs. Conclusions : This present investigation is the first clinical experience in Peru with DAAs for chronic hepatitis C in HIV-positive patients. Virologic response, tolerability, and safety against daclatasvir and velpatasvir, each in conjunction or in combination with sofosbuvir, were optimal in the case series presented.

Social stigmatization in Turkish patients with chronic hepatitis B and C / Estigmatización social en pacientes turcos con hepatitis crónica B y C

Background and aim: Viral hepatitis is the most important cause of chronic hepatitis worldwide. Stigmatization is defined as a feeling of rejection and isolation of patients by society due to illness. There are no studies on chronic viral hepatitis in the literature in English, which has its own religious and socio-cultural structure. In our study, we aimed to investigate the presence of social stigmatism and psychosocial effects on patients with different stages of chronic viral hepatitis B and C. Methods: Forty-five patients with chronic hepatitis C and 114 patients with chronic hepatitis B were enrolled in the study. Berger's scale was used for stigmatization, composed of 40 four-point Likert items that have four subscales: personalized stigma, disclosure, negative self-image, and public attitude. Stigma score ranges between one and four. Stigma is accepted as present if the overall score is above two. Results: Overall the mean stigma scores were 1.97±0.58 and 2.14±0.57 for chronic hepatitis B and C, respectively. There was stigma in 47.4% of the patients with chronic hepatitis B, and 60% of the patients with chronic hepatitis C. Being male was the risk factor on overall stigma, disclosure and public attitude in chronic hepatitis C. Living in an urban setting was the risk factor on negative self-image in chronic hepatitis C and on personalized stigma and disclosure in chronic hepatitis B. Conclusions: To the best of our knowledge, this is the first study that provides qualitative information about chronic hepatitis-related stigma. Stigmatization is a major problem in Turkey and worldwide. We believe that increasing the knowledge of the patients and society by teaching about the transmission routes of the disease and focusing on vaccination studies will prevent stigmatization.(AU)

Antecedentes y objetivo: La hepatitis viral es la causa más importante de hepatitis crónica en todo el mundo. La estigmatización se define como un sentimiento de rechazo y aislamiento de los pacientes, por parte de la sociedad debido a su enfermedad. No hay estudios sobre la hepatitis viral crónica en la literatura inglesa, que tiene su propia estructura religiosa y sociocultural. En nuestro estudio, nos propusimos investigar la presencia del estigma social y los efectos psicosociales en los pacientes con diferentes fases de hepatitis viral crónica B y C. Métodos: Se incluyó en el estudio a 45 pacientes con hepatitis crónica C y 114 pacientes con hepatitis crónica B. Se utilizó la escala de Berger para la estigmatización, compuesta por 40 ítems Likert de cuatro puntos, con cuatro subescalas cada uno: estigma personalizado, revelación, imagen negativa de sí mismo y actitud pública. La puntuación del estigma oscila entre uno y cuatro. El estigma se acepta como presente si la puntuación general es superior a dos. Resultados: En general, la media de las puntuaciones de estigmatización fue de 1,97 ± 0,58 y 2,14 ± 0,57 para la hepatitis crónica B y C, respectivamente. El 47,4% de los pacientes con hepatitis crónica B y el 60% de los pacientes con hepatitis crónica C sufrieron estigmatización. El hecho de ser varón fue el factor de riesgo del estigma general, la revelación y la actitud pública en la hepatitis crónica C. Vivir en un entorno urbano fue el factor de riesgo de la imagen negativa de sí mismo en la hepatitis crónica C y el estigma personalizado y la revelación en la hepatitis crónica B. Conclusiones: Hasta donde sabemos, este es el primer estudio que proporciona información cualitativa sobre el estigma relacionado con la hepatitis crónica. La estigmatización es un problema importante en Turquía y en todo el mundo...(AU)

Social stigmatization in Turkish patients with chronic hepatitis B and C.

BACKGROUND AND AIM: Viral hepatitis is the most important cause of chronic hepatitis worldwide. Stigmatization is defined as a feeling of rejection and isolation of patients by society due to illness. There are no studies on chronic viral hepatitis in the literature in English, which has its own religious and socio-cultural structure. In our study, we aimed to investigate the presence of social stigmatism and psychosocial effects on patients with different stages of chronic viral hepatitis B and C. METHODS: Forty-five patients with chronic hepatitis C and 114 patients with chronic hepatitis B were enrolled in the study. Berger's scale was used for stigmatization, composed of 40 four-point Likert items that have four subscales: personalized stigma, disclosure, negative self-image, and public attitude. Stigma score ranges between one and four. Stigma is accepted as present if the overall score is above two. RESULTS: Overall the mean stigma scores were 1.97±0.58 and 2.14±0.57 for chronic hepatitis B and C, respectively. There was stigma in 47.4% of the patients with chronic hepatitis B, and 60% of the patients with chronic hepatitis C. Being male was the risk factor on overall stigma, disclosure and public attitude in chronic hepatitis C. Living in an urban setting was the risk factor on negative self-image in chronic hepatitis C and on personalized stigma and disclosure in chronic hepatitis B. CONCLUSIONS: To the best of our knowledge, this is the first study that provides qualitative information about chronic hepatitis-related stigma. Stigmatization is a major problem in Turkey and worldwide. We believe that increasing the knowledge of the patients and society by teaching about the transmission routes of the disease and focusing on vaccination studies will prevent stigmatization.

Resultados en vida real de los antivirales de acción directa en el tratamiento de la hepatitis C crónica / Real life results of direct acting antiviral in hepatitis C treatment

Objetivo: Los antivirales de acción directa han logrado tasas de respuesta viral sostenida muy elevadas desde su comercialización. El objetivo de este trabajo fue el análisis de la efectividad y seguridad de los antivirales de acción directa en pacientes infectados por el virus de la hepatitis C crónica.Métodos: Se incluyeron pacientes infectados con el virus de la hepatitis C (VHC) y coinfectados por VHC y virus de la inmunodeficiencia humana (VIH) que iniciaron tratamiento con antivirales de acción directa entre 2015-2019. Como variable de efectividad se midió la respuesta viral sostenida.Resultados: Se incluyeron 303 pacientes, 235 (77,56%) monoinfectados y 68 (22,44%) coinfectados. El genotipo de virus más prevalente fue el 1 en ambos grupos. La proporción de cirróticos fue superior en la población monoinfectada 38,3% vs. 20,6%; p=0,047). De los 303 pacientes, a 279 se le analizó la carga viral a las 12 semanas de tratamiento; un 97,8% (273/279) alcanzaron respuesta viral sostenida, confirmándose 6 fracasos virológicos. En un análisis de subgrupos, en la mayoría de grupos según la presencia o no de cirrosis, la coinfección VIH y el genotipo, la efectividad se situó próxima o por encima del 90%. El tratamiento fue seguro, con toxicidad leve y sólo una suspensión de tratamiento. Se detectaron interacciones medicamentosas potenciales en un 20% de los pacientes.Conclusiones: Los antivirales de acción directa presentaron una efectividad elevada, igual e incluso superior a la descrita en los ensayos clínicos, e incluso en subpoblaciones difíciles de tratar. (AU)

Objetive: Direct-acting antivirals have achieved high sustained viral response rates since their commercialization. The main objective of this study was the analysis of the efficacy and safety of direct-acting antivirals in patients infected with the chronic hepatitis C virus.Methods: Patients infected with hepatitis C virus (HCV) and co-infected with HCV and human immunodeficiency virus (HIV) who started treatment with direct-acting antiviral drugs between 2015-2019 were included. The sustained viral response was measured as the effectivity variable.Results: 303 patients were included, 235 (77.56%) were monoinfected and 68 (22.44%) were co-infected. Genotype 1 virus was the most prevalent 1 in both groups. The proportion of cirrhotic was higher in the monoinfected population (38.3% vs. 20.6%; p=0.047). Of the 303 patients, 279 pacients had viral load analysis at 12 weeks of treatment, 97.8% (273/279) achieved sustained viral response and 6 virological failures were confirmed. In a subgroup analysis, the majority of the groups, regardless of the presence or not of cirrhosis, HIV coinfection or genotype, the efficacy was close to or above 90%. The treatment was safe, with mild toxicity and only one treatment suspension. Potential drug interactions were detected in 20% of patients.Conclusions: Direct-acting antivirals with a high efficacy, equal to or greater than that described in clinical trials, and even with subpopulations difficult to treat. (AU)

Production of insulin-like growth factor-binding proteins during the development of hepatic fibrosis due to chronic hepatitis C. / Producción de las proteínas de unión al factor de crecimiento insulinoide durante el desarrollo de la fibrosis hepática por hepatitis C crónica.

INTRODUCTION AND AIMS: Insulin-like growth factor 1 is modulated by the insulin-like growth factor-binding proteins (IGFBPs) that are synthesized in the liver. The aim of the present study was to evaluate the concentrations of IGFBPs 1-7 in patients with chronic hepatitis C and study their association with fibrosis stage. PATIENTS AND METHODS: A prospective, cross-sectional study was conducted that included patients with chronic hepatitis C. The stages of fibrosis were determined through FibroTest and FibroScan and the patients were compared with a control group. Serum levels of IGFBPs 1-7 were quantified through multiple suspension arrays. The Kruskal-Wallis test, Mann-Whitney U test, Spearman's correlation, and ROC curves were used for the statistical analysis. RESULTS: Upon comparing the patients and controls, the highest concentrations were found in IGFBPs 1, 2, 4, and 7 (p=0.02, p=0.002, p=0.008, and p<0.001, respectively). IGFBP-3 levels had a tendency to be lower in the patients (p=0.066), whereas values were similar between patients and controls for IGFBP-5 and 6 (p=0.786 and p=0.244, respectively). Of the seven IGFBPs, IGFBP-3 concentrations were the highest. There were significant differences between fibrosis stages for IGFBP-5 and IGFBP-7. CONCLUSION: IGFBPs play a relevant role in the fibrotic process in liver damage. IGFBP-7, in particular, differentiates fibrosis stages, making it a potential serum biomarker.

Enfermedades hepáticas y su relación con hiperglicemia / The relationship between liver diseases and hyperglycemia

La Diabetes Mellitus tipo 2 (DM2) y las enfermedades crónicas del hígado(ECH), definida para esta revisión como cualquier alteración funcional o estructural de este órgano, desde inflamación hasta fibrosis, son patologías que frecuentemente se asocian, y su coexistencia se relaciona con peor pronóstico y mayores complicaciones de ambas entidades. El objetivo de este artículo es describir la relación entre hiperglicemia y enfermedades del hígado, sus procesos fisiopatológicos comunes y tratamiento, distinguiendo las patologías más relevantes, entre ellas la Diabetes Hepatogénica (DH), la enfermedad hepática por Virus Hepatitis C (VHC) y la Enfermedad Hepática Grasa No Alcohólica (EHGNA). La DH es aquella diagnosticada en pacientes con cirrosis asociada a insuficiencia hepática, sin antecedentes previos de alteración de la glicemia. En la actualidad el diagnóstico se realiza en etapas tardías de la enfermedad. El VHC tiene un efecto diabetogénico conocido. Algunas terapias antivirales usadas para VHC evidencian mejoría de las alteraciones metabólicas al lograr respuestas virológicas sostenidas. En DM2, la EHGNA es frecuente, con mayor incidencia de fibrosis, hepatocarcinoma (HCC) y riesgo cardiovascular (RCV). Es necesario realizar una pesquisa e intervención precoz de EHGNA a los pacientes con DM2. En el manejo de éstos, la baja de peso ha demostrado ser efectiva en el control glicémico y en la mejoría histológica. Dentro de las terapias antidiabéticas, además del uso de metformina, debería considerarse aquellas que han demostrado a la fecha beneficios en EHGNA, como son tiazolidinedionas (pioglitazona) y/o análogos de GLP-1 (liraglutide) y optimizar el control de otros factores de RCV.

Type 2 Diabetes Mellitus (DM2) and chronic liver diseases (CLD) defined in this revision as any functional or structural alteration in the organ, covering from inflammation to fibrosis, are pathologies that are frequently associated, and when found together are related to worse prognosis and higher complications in both conditions. The objective of this article is to describe the relationship between hyperglycemia and liver diseases, their common physio-pathological processes and treatments, identifying the most important pathologies, including Hepatogenic Diabetes (HD), Hepatitis C Virus (HCV) liver disease and Non-Alcoholic Fatty Liver Disease (NAFLD). Hepatogenic diabetes (HD) is diagnosed in patients with liver failure associated to cirrhosis with no previous record of impaired glycemia. Currently, diagnosis is made during the late stages of the disease. Hepatitis C virus (HCV) has a known diabetogenic effect. Some antiviral therapies used for HCV show improvement in metabolic alterations by achieving sustained virological responses. Non-alcoholic fatty liver disease (NAFLD) in DM2 patients is common, presenting higher risk for fibrosis, hepatocellular carcinoma (HCC) and increased cardiovascular risk (CVR). Early screening and interventions for NAFLD in DM patients are necessary. Weight loss has been shown to be effective in glycemic control and histological improvement. Anti-diabetic therapies, in addition to the use of metformin, should consider therapies that have shown benefits for managing NAFLD, such as thiazolidinedione (pioglitazones) and/or aGLP-1 (Liraglutide), and optimally controlling other cardiovascular risk (CVR) factors.

Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI / Pathophysiology of Hepatitis C and Diabetes Mellitus: Towards the cure of two epidemics in the 21 st century

Resumen La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.

Abstract Chronic hepatitis C virus (HCV) and diabetes mellitus (DM) are two public health problems that impact health care systems with overall high costs. HCV infections cause liver manifestations such as hepatitis, cirrhosis and hepatocellular carcinoma. They have also been involved in the pathogenesis of extrahepatic manifestations among which are metabolic disorders such as DM. Longitudinal and cross-sectional studies have reported a higher incidence and prevalence of DM in patients with chronic HCV infections. DM accelerates histological and clinical progression of chronic HCV infections and leads to cardiovascular complications. Recently, progress has been made in treatment with the introduction of new medications such as direct-acting antiviral drugs that improve glycemic control in these patients.

Experiencia peruana en el tratamiento de hepatitis crónica C con las nuevas drogas antivirales de acción directa / Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs

Objetivos: La terapia ideal para la hepatitis crónica C consiste en el uso de drogas antivirales de acción directa (DAA). En el Perú la experiencia en vida real con DAA no se conoce, por lo que el objetivo del presente estudio es reportar la alta eficacia terapéutica con estos esquemas. Material y métodos: Mediante correo electrónico se invitó a participar a través de una encuesta a médicos hepatólogos a nivel nacional. Se incluyeron los datos de 4 médicos. Los resultados fueron analizados con estadística descriptiva. Resultados: Se incluyeron 63 pacientes, la edad promedio fue 59 años, varones fueron 49,21%, cirrosis estuvo presente en el 49,21% (31/63), 34,92% había sido no respondedor a terapia con PEGIFN/RBV. El Genotipo 1 estuvo presente en 93,65% de casos, siendo el 1a el predominante (58,73%). Solo hubo dos casos de genotipo 2 y uno de genotipo 3. Se utilizaron 10 esquemas de combinación con DAA, siendo los más eficaces, Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/ Ribavirina y Sofosbuvir/Simeprevir, en todos ellos se logró Respuesta Viral Sostenida (RVS) de 100%. Con los otros 7 esquemas la RVS fue menor a 90% o solo se había incluido uno o dos pacientes. La tolerancia a la terapia fue adecuada y todos los pacientes culminaron la terapia. Conclusiones: En vida real los esquemas de terapia antiviral para hepatitis C con DAA tienen alta eficacia y seguridad. Las mejores respuestas se obtuvieron con Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina y Sofosbuvir/Simeprevir. Esta data puede ser útil para considerar estrategias de tratamiento con el enfoque de salud pública.

Objective: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. Material and methods: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. Results: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/ Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. Conclusions: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.

Nuevos progresos en el enfrentamiento a la hepatitis C / New progresses in hepatitis C management

RESUMEN El virus de la hepatitis C es la principal infección trasmitida por los derivados de la sangre en los Estados Unidos, con 3.2 millones de individuos infectados. El alfa interferón inyectable ha sido históricamente la piedra angular en la terapia del virus de hepatitis C. Se revisaron las publicaciones los trabajos publicados en Medline, Scielo, PubMed, e Hinari, hasta comienzos del año 2016. Las principales palabras clave utilizadas fueron virus de la hepatitis C, hepatitis C crónica, Interferón, antivirales. Recientes adelantos han llevado a la disponibilidad de nuevos medicamentos antivirales, que con el desarrollo de nuevas terapias orales libres de interferón han convertido la terapia del virus de la hepatitis C más eficaz además de simplificar los regímenes del tratamiento. Aunque estos regímenes de tratamiento aún permanecen complicados, las nuevas recomendaciones y guías evolucionan rápidamente. El rápido desarrollo de nuevas terapias para la hepatitis C, han logrado métodos más eficaces con menos reacciones adversas que optimizan el tratamiento de estos enfermos (AU).

ABSTRACT The hepatitis C virus is the main infection transmitted by blood products in the United States, with 3.2 million of infected individuals. The injected alpha interferon has historically been the key stone in the therapy of the hepatitis C virus. The works published in Medline, Scielo, PubMed and Hinary until the beginning of 2016 were reviewed. The main used key words were HVC, cronic hepatitis C, interferon, antivirals. Recent advances have led to the availability on new antiviral drugs, developing new interferon-free oral therapies that make the therapy of hepatitis C virus more efficacious and make easier the treatment regimens. Although these treatment regimens are still complicated, the new recommendations and guidelines evolve quickly. The fast development of new therapies against hepatitis C has led to more efficacious methods with less adverse reactions, optimizing the treatment of these patients (AU).

Nuevos progresos en el enfrentamiento a la hepatitis C / New progresses in hepatitis C management

RESUMEN El virus de la hepatitis C es la principal infección trasmitida por los derivados de la sangre en los Estados Unidos, con 3.2 millones de individuos infectados. El alfa interferón inyectable ha sido históricamente la piedra angular en la terapia del virus de hepatitis C. Se revisaron las publicaciones los trabajos publicados en Medline, Scielo, PubMed, e Hinari, hasta comienzos del año 2016. Las principales palabras clave utilizadas fueron virus de la hepatitis C, hepatitis C crónica, Interferón, antivirales. Recientes adelantos han llevado a la disponibilidad de nuevos medicamentos antivirales, que con el desarrollo de nuevas terapias orales libres de interferón han convertido la terapia del virus de la hepatitis C más eficaz además de simplificar los regímenes del tratamiento. Aunque estos regímenes de tratamiento aún permanecen complicados, las nuevas recomendaciones y guías evolucionan rápidamente. El rápido desarrollo de nuevas terapias para la hepatitis C, han logrado métodos más eficaces con menos reacciones adversas que optimizan el tratamiento de estos enfermos (AU).

ABSTRACT The hepatitis C virus is the main infection transmitted by blood products in the United States, with 3.2 million of infected individuals. The injected alpha interferon has historically been the key stone in the therapy of the hepatitis C virus. The works published in Medline, Scielo, PubMed and Hinary until the beginning of 2016 were reviewed. The main used key words were HVC, cronic hepatitis C, interferon, antivirals. Recent advances have led to the availability on new antiviral drugs, developing new interferon-free oral therapies that make the therapy of hepatitis C virus more efficacious and make easier the treatment regimens. Although these treatment regimens are still complicated, the new recommendations and guidelines evolve quickly. The fast development of new therapies against hepatitis C has led to more efficacious methods with less adverse reactions, optimizing the treatment of these patients (AU).

Comorbidity, concomitant medication, use of resources and healthcare costs associated with chronic hepatitis C virus carriers in Spain. / Comorbilidad, medicación concomitante, uso de recursos y costes sanitarios asociados a los pacientes portadores del virus de la hepatitis C crónica en España.

OBJECTIVES: To assess the comorbidity, concomitant medications, healthcare resource use and healthcare costs of chronic hepatitis C virus patients in the Spanish population. PATIENTS AND METHODS: Retrospective, observational, non-interventional study. Patients included were≥18 years of age who accessed medical care between 2010-2013. Patients were divided into 2 groups based on the presence or absence of liver cirrhosis. The follow-up period was 12 months. Main assessment criteria included general comorbidity level (determined by the resource utilisation band score) and prevalence of specific comorbidities, concomitant medications, healthcare resource use and healthcare costs. Statistical analysis was performed using regression models and ANCOVA, P<.05. RESULTS: One thousand fifty-five patients were enrolled, the mean age was 57.9 years and 55.5% were male. A percentage of 43.5 of patients had a moderate level of comorbidity according to the resource utilisation band score. The mean time from diagnosis was 18.1 years and 7.5% of the patients died during the follow-up period. The most common comorbidities were dyslipidaemia (40.3%), hypertension (40.1%) and generalised pain (38.1%). Cirrhosis was associated with cardiovascular events (OR 3.8), organ failures (OR 2.2), alcoholism (OR 2.1), diabetes (OR 1.2) and age (OR 1.2); P<.05. The most commonly used medications were anti-infectives (67.8%) and nervous system medications (66.8%). The mean total cost per patient was 3,198€ (71.5% healthcare costs, 28.5% indirect/non-healthcare costs). In the corrected model, the total costs per patient-year were 2,211€ for those without cirrhosis and 7,641€ for patients with cirrhosis; P<.001. CONCLUSIONS: Chronic hepatitis C virus patients are associated with a high level of comorbidity and the use of concomitant medications, especially in patients with liver cirrhosis. Chronic hepatitis C virus infection represents a substantial economic burden on the Spanish National Health System.

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.

Porfiria cutánea tarda como manifestación extrahepática de hepatitis C crónica: reporte de un caso / Porphyria cutanea tarda as extrahepatic manifestation of chronic hepatitis C: a case report

Se presenta el caso de un paciente varón de 56 años quien es evaluado por presentar a nivel del dorso de ambas manos cicatrices hiperpigmentadas e hipopigmentadas, asociadas a quistes de milia. Se le realizó estudios del metabolismo de las porfirinas y biopsia cutánea de las lesiones los cuales resultaron compatibles con porfiria cutánea tarda. En el laboratorio inicial se encontró elevación de los valores de transaminasas, identificándose posteriormente infección crónica por virus de hepatitis C. Con la finalidad de tratar la infección viral y resolver el compromiso dérmico, considerado como manifestación extrahepática del virus hepatitis C, se inició tratamiento con interferón pegilado y ribavirina evolucionando favorablemente con respuesta viral rápida, carga viral no detectable hasta la actualidad (36 semanas de tratamiento), disminución del nivel de transaminasas séricas y mejoría de las lesiones dérmicas.

The present case is a 56 year old male who present hyperpigmented and hypopigmented scars in both hands, associated with the presence of milia cysts. It was studied the metabolism of porphyrins and skin biopsy of the lesions which were compatible with porphyria cutanea tarda. In the initial laboratory, elevated transaminases values were found and subsequently identified chronic infection of hepatitis C virus. In order to treat viral infection and resolve the dermal commitment; considered extrahepatic manifestation of hepatitis C virus, treatment was started with pegylated interferon and ribavirin, with favorably development and rapid viral response, with undetectable viral load until now (24 weeks of treatment), decreased level of serum transaminases and improvement of skin lesions.

Cost-effectiveness analysis of two treatment strategies for chronic hepatitis C before and after access to direct-acting antivirals in Spain. / Análisis coste-efectividad de dos estrategias de tratamiento para la hepatitis C crónica: antes y después del acceso a los agentes antivirales de acción directa en España.

OBJECTIVE: To evaluate the cost-effectiveness of a strategy based on direct-acting antivirals (DAAs) following the marketing of simeprevir and sofosbuvir (post-DAA) versus a pre-direct-acting antiviral strategy (pre-DAA) in patients with chronic hepatitis C, from the perspective of the Spanish National Health System. METHODS: A decision tree combined with a Markov model was used to estimate the direct health costs (€, 2016) and health outcomes (quality-adjusted life years, QALYs) throughout the patient's life, with an annual discount rate of 3%. The sustained virological response, percentage of patients treated or not treated in each strategy, clinical characteristics of the patients, annual likelihood of transition, costs of treating and managing the disease, and utilities were obtained from the literature. The cost-effectiveness analysis was expressed as an incremental cost-effectiveness ratio (incremental cost per QALY gained). A deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. RESULTS: The post-DAA strategy showed higher health costs per patient (€30,944 vs. €23,707) than the pre-DAA strategy. However, it was associated with an increase of QALYs gained (15.79 vs. 12.83), showing an incremental cost-effectiveness ratio of €2,439 per QALY. The deterministic sensitivity analysis and the probabilistic sensitivity analysis showed the robustness of the results, with the post-DAA strategy being cost-effective in 99% of cases compared to the pre-DAA strategy. CONCLUSIONS: Compared to the pre-DAA strategy, the post-DAA strategy is efficient for the treatment of chronic hepatitis C in Spain, resulting in a much lower cost per QALY than the efficiency threshold used in Spain (€30,000 per QALY).

[Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis]. / Análisis coste-efectividad de sofosbuvir, interferón pegilado y ribavirina en pacientes con hepatitis crónica por virus C: tratamiento precoz en fases iniciales de fibrosis vs. tratamiento tardío en fases avanzadas.

AIMS: Cost-effectiveness analysis of sofosbuvir combined with peginterferon alpha-2a and ribavirin (SOF/Peg-IFN/RBV) in early versus advanced fibrosis in previously untreated patients with chronic hepatitis C genotype 1 (CHC-GT1), from the perspective of the Spanish National Health System (NHS). METHODS: A Markov model was developed to compare lifetime costs and outcomes (life years gained [LYGs] and quality-adjusted life years [QALYs]) of 2 treatment strategies: SOF/Peg-IFN/RBV administered during early fibrosis (mild-moderate fibrosis; F2-F3) or advanced fibrosis (cirrhosis; F4). Efficacy (sustained virologic response), annual transition probabilities, disease management costs and utilities were obtained from the literature. Costs and outcomes were discounted annually at 3%. Direct costs were considered, expressed in Euros (€, 2014). Probabilistic sensitivity analysis (PSA) was also performed. RESULTS: SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€43,263) was less than the cost of treatment in the advanced stage (€49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations. CONCLUSIONS: Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients.

[Incidence, management and costs of adverse effects in chronic hepatitis C patients on triple therapy with telaprevir or boceprevir: first 12 weeks of treatment]. / Incidencia, manejo y coste de los efectos adversos hematológicos y dermatológicos durante las 12primeras semanas de tratamiento con triple terapia para hepatitisC.

INTRODUCTION: The aim of the study was to analyze the incidence, management and cost associated to hematological and dermatological adverse effects (AE) in chronic hepatitis C patients on triple therapy (TT) with telaprevir (TVR) or boceprevir (BOC). METHODS: An analysis was made on the data recorded on patients who started treatment with TVR or BOC associated with peginterferon alfa and ribavirin in a 12-week follow-up period. RESULTS: Fifty-three patients were included (TVR n=36; BOC n=17). Thrombocytopenia (83% TVR vs. 88% BOC) followed by neutropenia (89% TVR vs. 82% BOC) were the most common AE. Dermatological AE were observed in 32% of patients. Eleven patients required treatment discontinuation (all of them received TVR), and toxicity was the main reason for discontinuation (64%). The percentage of patients who required supportive treatment for management of AE was 66%. The most used supportive treatment was erythropoietin. Eight patients required emergency health care, and 2 were hospitalized due to AE. Total cost of additional supportive resources was 32,522€ (625 [SD=876]€/patient) (TVR 759 [SD=1,022]€/patient vs. BOC 349 [SD=327]€/patient; P>.05). Patients with gradeiii-iv toxicity required greater supportive care with higher costs, compared to patients with gradei-ii toxicity (849 [SD=1,143]€/patient vs. 387 [SD=397]€/patient; P=.053). CONCLUSION: The addition of new protease inhibitors to conventional treatment leads to a higher incidence of hematological AE in our study, compared to data described in clinical trials. The elevated incidence of AE involves the use of supportive care, increasing total costs of therapy.

Avaliação do processo de dispensação de medicamentos aos portadores de hepatite C crônica em farmácias de componentes especializados da Secretaria de Estado da Saúde de São Paulo, em 2010 / Evaluation of medication dispensation to patients with chronic hepatitis C in São Paulo State Health Department specialized unit pharmacies, Brazil, in 2010 / Evaluación del proceso de dispensación de medicamentos a los portadores de hepatitis C crónica en farmacias de componentes especializados de la Secretaría de Estado de la Salud de São Paulo, en 2010

Objetivo: avaliar a dispensação dos medicamentos para o tratamento da hepatite viral C crônica verificando sua adequação às recomendações do Ministério da Saúde e estimar gastos com a dispensação inadequada dos medicamentos. Métodos: estudo transversal descritivo sobre 643 prontuários de pacientes portadores de hepatite viral C crônica cadastrados em 2010, em quatro farmácias do Sistema de Dispensação de Medicamentos Excepcionais da Secretaria de Estado da Saúde de São Paulo (SES/SP). Resultados: foram identificadas diferenças expressivas entre as farmácias, em relação ao processo de dispensação dos medicamentos; com base nos laudos das biópsias, estimou-se que 64,5 por cento dos pacientes teriam indicação de tratamento e que R$1.096.132,32 foram despendidos com o tratamento de pacientes em não conformidade com as diretrizes terapêuticas. Conclusão: faz-se necessária uma padronização mais rigorosa nos procedimentos de dispensação de medicamentos para o tratamento da hepatite C crônica na rede pública da SES/SP...

Objective: to assess whether the medication dispensing procedures for chronic viral hepatitis C treatment follow Ministry of Health guidelines and to estimate possible costs of inadequate procedures. Methods: this was a descriptive cross-sectional study of 643 medical records of patients with chronic viral hepatitis C registered in 2010 with four São Paulo State Health Department (SES/SP) Exceptional Drug Dispensing System pharmacies. Results: relevant discrepancies regarding medication dispensing procedures were detected. Based on the histopathology reports it was estimated that only 64.5 per cent of assessed patients actually met the guideline criteria for treatment and therefore R$ 1,096,132.32 was spent in nonconformity with the guidelines. Conclusion: a more rigorous standardization of procedures for dispensing medication for the treatment of chronic hepatitis C in SES/SP Public Health Services must be implemented...

OBJETIVO: evaluar la dispensación de los medicamentos para el tratamiento de la hepatitis viral C crónica, verificando su adecuación a las recomendaciones del Ministerio de Salud y estimar gastos con la dispensación inadecuada de los medicamentos.MÉTODOS: estudio transversal descriptivo sobre 643 prontuarios de pacientes portadores de hepatitis viral C crónica registrados en 2010, en cuatro farmacias del Sistema de Dispensación de Medicamentos Excepcionales de la Secretaría de Estado de la Salud de São Paulo (SES/SP).RESULTADOS: se identificaron diferencias expresivas entre las farmacias, en relación al proceso de dispensación de los medicamentos; con base en los laudos de las biopsias, se estimó que 64,5% de los pacientes tendría indicación de tratamiento y que se gastaron R$ 1.096.132,32 con el tratamiento de pacientes en no-conformidad con las directrices terapéuticas.CONCLUSIÓN: es necesaria una estandarización más rigurosa en los procedimientos de dispensación de medicamentos para el tratamiento de la hepatitis C crónica en la red pública de la SES/SP...

Hepatitis C crónica: aspectos clínicos, serológicos y de tratamiento en dos centros de atención en Bogotá, Colombia / Clinical Issues, Serological issues and Treatment of Chronic Hepatitis C at Two Medical Centers in Bogotá, Colombia

Introducción: el virus de la hepatitis C afecta a cerca de 170 millones de personas en el mundo. La organización mundial de la salud (OMS) estima una prevalencia mundial del 2%. La respuesta global al tratamiento en la era de la terapia dual para genotipo 1 es del orden de 40%. En Colombia hay datos limitados que confirmen un comportamiento similar y que describan las características clínicas de los pacientes con esta infección. Metodología: se revisaron retrospectivamente las historias clínicas de pacientes con diagnóstico de hepatitis C crónica que asistieron a consulta externa del servicio de Hepatología en la Clínica Universitaria Colombia y de la consulta externa del servicio de Hepatología de uno de los autores durante el periodo comprendido entre el 1 de enero del 2010 y el 30 de mayo de 2013, se describen las características clínicas, serológicas y de respuesta al tratamiento. Resultados: se evaluaron las historias clínicas de 163 pacientes, 62% mujeres y 38% hombres, con una edad promedio de 58,2 años. El principal factor de riesgo para la adquisición de la hepatitis C fue historia de transfusiones antes de 1992 en 62% de los pacientes. La decisión de iniciar tratamiento se tomó en 77 pacientes (47,2%) y en 86 (52,8%) no se inició por diferentes razones dentro de las cuales la edad avanzada y cirrosis avanzada suman más de 50%; otras razones para no iniciar el tratamiento fueron: enfermedad mínima (4,7%), enfermedad mínima más edad avanzada (10,5%), curación espontánea (14%), poca probabilidad de respuesta (3,3%) y otras (14%). De 62 pacientes de los que se contaba con información acerca de tratamientos previos o tratados recientemente 30,6% presentaron respuesta viral sostenida (RVS), 29,0% fueron clasificados como reincidentes o relapser, 8,1% como respondedores parciales, 19,4% no tuvieron respuesta y 12,9% suspendieron el tratamiento por intolerancia. Conclusiones: el antecedente más frecuente para la adquisición del VHC en el grupo de pacientes estudiado fue la historia de transfusiones antes de 1992 asociada con cirugía ginecológica. Cerca de la mitad de los pacientes se diagnostican tardíamente. Se muestra una mayor tendencia al tratamiento de la hepatitis con tasas de RVS similares a las encontradas en otras series. Este estudio abre puertas a la realización de otros que permitan definir de forma más amplia la prevalencia, factores de riesgo y variables de respuesta al tratamiento de esta entidad en nuestro país.

Introduction: Hepatitis C affects about 170 million people worldwide. The World Health Organization (WHO) has estimated global prevalence at 2%. Overall, about 40% of patients respond to dual therapy treatment for genotype. In Colombia data available for confirm a similar pattern and for describing the clinical characteristics of patients with this infection are scarce. Methods: Medical records of patients in the Hepatology outpatient service at the Clínica Universitaria Colombia who had been diagnosed with chronic hepatitis C by one of the authors between January 1, 2010 and May 30, 2013 were retrospectively reviewed for clinical characteristics, serological characteristics and treatment responses. Results: The medical records of 163 patients were evaluated: 62% were female, 38% were male, and their mean age was 58.2 years. The main risk factor for acquiring hepatitis C was a history of transfusions before 1992. This factor was present in 62% of the patients. The decision to start treatment was made for 77 patients (47.2%), but 86 patients (52.8%) did not start treatment. Reasons included advanced age and advanced cirrhosis which together accounted for more than 50% of these patients. Other reasons for not starting treatment were minimal disease (4.7%), minimal sign of disease plus advanced age (10.5%), spontaneous healing (14%), low probability of response (3.3%) and others (14%). Of the 62 patients for whom information about previous or recent treatments was available, 30.6% had sustained virological responses (SVR), 29.0% were classified as relapsers, 8.1% as partial responders, 19.4% had no response, and 12.9% discontinued treatment because of intolerance. Conclusions: The most frequent antecedent of HCV in the group of patients studied a history of transfusions associated with gynecological surgery before 1992. About half of the patients were diagnosed late. Hepatitis was more likely to have been treated in these patients than in patients in other studies, but the SVR rate was similar to those found in other series. This study opens doors to the realization of other studies to more broadly define the prevalence, risk factors and treatment response variables of this entity in our country.

Directly observed therapy for chronic hepatitis C: a randomized clinical trial in the prison setting.

BACKGROUND: The diagnosis and treatment of chronic hepatitis C are major concerns in prisons. OBJECTIVES: The aim of this randomized clinical trial was to determine the extent to which directly observed therapy (DOT) improved the efficacy of the standard treatment for chronic hepatitis C in the prison setting. PATIENTS AND METHODS: A randomized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent standard treatment for chronic hepatitis C (based on pegylated interferon alpha-2a and ribavirin). RESULTS: A total of 252 inmates were randomized, of which 244 were analyzed: 109 in the DOT group and 135 in the non-DOT group. The mean age was 35.88 years (SD 6.54), 94.3% were men, 72.1% reported intravenous drug use, 21.3% were HIV co-infected, and 55.3% had genotype 1 or 4. The patients received the study treatment for a median time of 33.9 weeks in the overall sample. Sustained virological response was achieved in 60.6% (95% CI, 51.17-69.22) of the DOT group and in 65.9% (95% CI, 57.59-73.38) of the standard therapy group (risk ratio=0.92; 95% CI, 0.76-1.12). The mean proportion of patients continuing the treatment was 83% (SD=31). Adverse events were reported in 93.4% of the patients, and serious adverse events were reported in 8.2%, with no significant differences between groups. CONCLUSIONS: Sustained virological response was remarkably high, although there were no differences between groups, probably due to high treatment adherence.