Prevalence of the potential drug-drug interactions between pangenotypic direct-acting antivirals and the concomitant medications associated with patients with chronic hepatitis C virus infection in Spain. / Prevalencia de las potenciales interacciones medicamentosas entre los antivirales de acción directa pangenotípicos y la medicación concomitante asociada a los pacientes con infección del virus de la hepatitis C crónica en España.

OBJECTIVE: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain. METHODS: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05. RESULTS: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively. CONCLUSIONS: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions.

Autoantibodies to cytoplasmic rods and rings in patients with hepatitis C virus infection treated with direct-acting antivirals: The role of prior treatment with interferon plus ribavirin.

INTRODUCTION: The cytoplasmic rods-rings (RR) pattern is found in hepatitis C (HCV) patients treated with interferon-ribavirin when studied with ANA-IIF. Ribavirin aggregates/induces antigenic changes in IMPDH-2, an enzyme necessary for ribavirin action. PATIENTS AND METHOD: Prospective search for anti-RR autoantibodies (HEp-2, INOVA) in patients treated with direct-acting antivirals (DAAs) from October 2015 to June 2017. HCV-negative patients from up to June 2016 acted as controls. Anti-RR was analyzed at baseline and, mainly, during treatment and follow-up. The Chi-square test, Student's t-test and a logistic regression analysis were performed. RESULTS: Between October 2015 and June 2016, 1258 men and 2389 women who were HCV-negative and 137 men and 112 women who were HCV-positive patients were studied. Approximately 22.9% of HCV-negative and 13.2% of HCV-positive were ANA-IIF-positive (p<0.05). Three HCV-negative (0.08%) and 23 (9.2%) HCV-positive patients had anti-RR (p<0.001). A total of 122 patients received DAAs; 30 received DAA+RBV; 46 pre-treated with IFN-RBV received DAA; 31 pre-treated with IFN-RBV received DAA+RBV; 16 received IFNpeg-RBV; and 24 received IFN-RBV-DAA. None of the 122 DAA-treated patients showed anti-RR; anti-RR were identified in 14.8% of those treated with DAA-RBV; in 25.9% of those pre-treated with IFN-RBV receiving DAA; in 22.2% of IFN-RBV-pre-treated patients who received DAA+RBV; in 7.4% of those treated with IFNpeg-RBV and in 29.6% of those treated with IFNpeg-RBV-DAA. The multivariate analysis showed significant associations between anti-RR and "Exposure to IFN" and "Time of exposure to RBV". CONCLUSIONS: Anti-RR autoantibodies were detected only in patients with current or past treatments with RBV, even in cases in which only DAAs were later administered.

Factors influencing hepatitis C cure in the era of direct-acting antivirals. / Factores que influyen en la curación de la hepatitis C en la era de los antivirales de acción directa.

Direct-acting antiviral agents are highly potent drugs with a strong genetic barrier. Consequently, the factors influencing hepatitis C cure have been reduced and have progressively lost importance. Host factors, such as the presence of cirrhosis, race, and treatment adherence, influence sustained viral response. Adherence, together with treatment errors and drug interactions, are also important, especially in older patients. Viral factors, such as viral load, genotype, and the presence of baseline resistances affect the response rate but their influence can be minimised by using pan-genotypic regimens. Treatment simplification and the high efficacy of new antiviral treatments will allow treatment universalisation and will hopefully enable elimination of the infection in the next few decades. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

Role of ribavirin in interferon-free therapy for the treatment of hepatitisC virus. / Papel de la ribavirina en la terapia libre de interferón frente al virus de la hepatitisC.

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment.

Hepatitis C-related cirrhosis. Current status. / Cirrosis por hepatitis C. Estado actual.

Chronic hepatitis C virus (HCV) infection affects around 150 million people. It is a leading cause of liver related morbidity and mortality through its predisposition to liver fibrosis, cirrhosis and end-stage liver complications. New treatments based on direct-acting antivirals have opened a new era in the management of HCV cirrhosis. They allow for HCV eradication without substantial side effects in almost all cirrhotic patients, reducing the risk of hepatocellular carcinoma, liver decompensation and mortality. This review provides an update on HCV cirrhosis. The paper focuses on the disease burden and major progresses in the diagnosis, follow-up and treatment of this patient subgroup.

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.

[The value of genetics in the era of hepatitis C triple therapy]. / Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C.

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.

Tratamiento de la hepatitis crónica por virus C con interferón pegilado cubano y ribavirina / Treatment of chronic hepatitis C with Cuban pegylated interferon and ribavirin

Introducción: es en la actualidad la asociación de interferón pegilado y ribavirina la terapia más aceptada internacionalmente para el tratamiento de la hepatitis crónica C. En el 2011 comienza la aplicación en Matanzas de dicha combinación, utilizándose el interferón pegilado cubano (PEG-Heberon), con el cual se abrió un nuevo camino en el manejo terapéutico de esta enfermedad. Objetivo: describir los primeros resultados en Matanzas de la aplicación del PEG-Heberon y la ribavirina en el tratamiento de la hepatitis crónica C. Métodos: estudio descriptivo-prospectivo. Universo, 19 pacientes procedentes de la Consulta Provincial de Hepatología del Hospital Universitario Clínico Qurúrgico Comandante Faustino Pérez. Las variables estudiadas fueron: sexo, grupo etáreo, tipo de paciente, forma de presentación, efectos adversos, conducta ante estos, respuestas bioquímica y virológica al tratamiento. Resultados: predominaron los pacientes del sexo femenino (57,9 %), edad promedio de 41,7 ± 9,2 años, vírgenes de tratamiento (73,7 %) y con forma clínica asintomática (68,4 %). Se registraron efectos adversos en el 100 % de los casos, todos los clínicos fueron leves y entre los hematológicos el 70,4 % resultaron leves. No se reportaron eventos graves ni suspensiones del tratamiento. Se obtuvo respuesta bioquímica al concluir tratamiento en el 89,4 % y sostenida en el 78,9 %. La virológica se logró en el 78,9 % al término del tratamiento y en el 68,4 % seis meses después de este. Conclusión: se logró una elevada adherencia a la terapia combinada resultando tolerada y segura para los pacientes con tasas aceptables de respuesta virológica sostenida (RVS).

Introduction: currently, the association of pegylated interferon and ribavirin is internationally the most accepted therapy for the treatment of chronic hepatitis C. The application of this combination began in Matanzas in 2011, using the Cuban pegylated interferon (PEG-Heberon), setting up a new way in the therapeutic management of this disease. Objective: to describe the first results of the PEG-Heberon and ribavirin application in the treatment of chronic hepatitis C in Matanzas. Methods: descriptive- prospective study. Universe: 19 patients from the provincial consultation of Hepatology of the University Clinic-surgical Hospital Comandante Faustino Pérez in the period from October 2011 to October 2013. The studied variables were: sex, age groups, type of patient, presentation way, adverse reactions, behavior against them, biochemical and virologic answers to treatment. Results: there it was a predominance of female patients (57,9 %); the average age was 41,7 ± 9,2 years; treatment-virgins (73,7 %) and asymptomatic clinical forms (68,4 %). There were adverse reactions in 100 % of the cases; all the clinical ones were mild and among the hematologic ones, 70,4 % were light. There were neither serious events nor cancelations of the treatment. There was a biochemical answer at the end of the treatment in 89,4 % and a maintained one in 78,9 %. The virological answer was achieved at the end of the treatment in 78,9 %, and six months after treatment in 68,4 % of the patients. Conclusion: a high adherence to the combined therapy was achieved, being tolerated and safe for the patient, with acceptable rates of continuous virological answers.

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

INTRODUCTION: Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). OBJECTIVES: To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. METHODS: Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin ß 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin ß (B2; n=13). RESULTS: RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. CONCLUSIONS: G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin ß were safe and well tolerated (Clin Trials Gov NCT00830609).

Hepatitis crónica en pacientes, donantes o no de sangre, con anticuerpo al virus de la hepatitis C positivo / Chronic Hepatitis in Donors and Non-Blood Donors with Positive Antibodies to the Virus C

Introducción: la infección por el virus de la hepatitis C (VHC), problema de salud mundial, es una de las principales causas de hepatitis crónica y cirrosis hepática. Objetivo: identificar si existen diferencias en la frecuencia de presentación de la hepatitis crónica y sus características clínicas, humorales e histopatológicas, entre donantes y no donantes de sangre con anticuerpos al VHC (anti-VHC) positivo. Métodos: el universo de estudio estuvo compuesto por la totalidad de pacientes con anti-VHC positivo, diagnosticado por ultramicroelisa en el Banco Provincial de Sangre, atendidos entre enero 2000-diciembre 2011, en una Consulta Especializada del Hospital General Universitario Vladimir Ilich Lenin de Holguín. Se realizó biopsia hepática a los pacientes. Se seleccionaron dos muestras intencionadas de pacientes con diagnóstico de hepatitis crónica, grupo estudio, 46 donantes y grupo control, 17 no donantes, sin antígeno de superficie del virus B o tratamiento previo de interferón y ribavirina. Resultados: la hepatitis crónica fue mayor (P<0,05) en el grupo control, con formas activas más severas con o sin fibrosis (P<0,001), y alaninoaminotransferasas (ALAT) alteradas (p<0,001), a diferencia del grupo estudio con predominio de hepatitis con actividad ligera o mínima y ALAT normales. Los donantes sintomáticos fueron minoría a diferencia (p<0,001) de los no donantes, 82% con síntomas, en orden decreciente: astenia (14), molestia en hipocondrio derecho (12) y dispepsia (7). Conclusiones: la menor frecuencia de hepatitis crónica con anti-VHC positivo, en los donantes de sangre, con predominio de la actividad mínima y ligera, pudiera deberse al diagnóstico precoz en etapas iníciales de la enfermedad. Los donantes asintomáticos con transaminasas normales preponderaron, sobre los no donantes, lo que pudiera corresponderse con la magnitud de la actividad y el estadio de la hepatitis crónica en aquellos.

Introduction: the hepatitis C virus infection, problem of worldwide health is one of the main causes of chronic hepatitis and liver cirrhosis. Objective: to identify whether there are differences in the frequency of occurrence of chronic hepatitis and their clinical characteristics, humoral and pathological, between donors and non-blood donors with antibodies to HCV (anti-HCV) positive Methods: the study group comprised all patients with anti-HCV positive, diagnosed by ultramicroelisa in Provincial Blood Bank, treated from January 2000 to December 2011, in General University Hospital Vladimir Ilich Lenin of Holguin. Liver biopsy was performed to patients. Two intentional samples were selected: patients diagnosed with chronic hepatitis study group and control group 46 donors, 17 non-blood donors without virus surface antigen pretreatment B or interferon and ribavirin. Results: chronic hepatitis was higher (P <0.05) in the control group, with more active forms with or without severe fibrosis (P <0.001), and alaninoaminotransferasas (ALAT) altered (p <0.001), unlike the study group prevalence of hepatitis with mild activity or minimal and normal ALAT. Donors were minority symptomatic difference (p <0.001) than non-donors, 82% with symptoms, in decreasing order: asthenia (14), right upper quadrant discomfort (12) and dyspepsia (7). Conclusions: the lower frequency of chronic hepatitis with positive HCV in blood donors, predominantly minimal to slight activity, could be due to early diagnosis in early stages of the disease. Asymptomatic donors with normal transaminases predominated on non-donors, which could correspond to the magnitude of the activity and stage of chronic hepatitis those ones.

[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.

Hepatitis crónica en pacientes, donantes o no de sangre, con anticuerpo al virus de la hepatitis C positivo / Chronic Hepatitis in Donors and Non-Blood Donors with Positive Antibodies to the Virus C

Introducción: l a infección por el virus de la hepatitis C VHC, problema de salud mundial,es una de las principales causas de hepatitis crónica y cirrosis hepática.Objetivo: i dentificar si existen diferencias en la frecuencia de presentación de la hepatitis crónica y sus características clínicas, humorales e histopatológicas, entre donantes y no donantes de sangre con anticuerpos al VHC anti- VHC positivo. Métodos: el universo de estudio estuvo compuesto por la t otalidad de pacientes con anti-VHC positivo, diagnosticado por ultramicroelisa en el Banco Provincial de Sangre, atendidos entre enero 2000- diciembre 2011, en una Consulta Especializada del Hospital General Universitario Vladimir Ilich Lenin de Holguín. Se realizó biopsia hepática a los pacientes. Se seleccionaron dos muestras intencionadas de pacientes con diagnóstico de hepatitis crónica,grupo estudio, 46 donantes y grupo control, 17 no donantes, sin antígeno de superficie del virus B o tratamiento previo de interferón y ribavirina.Resultados: l a hepatitis crónica fue mayor P 0,05 en el grupo control, con formas activas más severas con o sin fibrosis P 0,001, y alaninoaminotransferasas ALAT alteradas p 0,001, a diferencia del grupo estudio con predominio de hepatitis con actividad ligera o mínima y ALAT normales(AU)...

Introduction: the hepatitis C virus infection, problem of worldwide health is one of the main causes of chronic hepatitis and liver cirrhosis.Objective: t o identify whether there are differences or not in the frequency of occurrence of chronic hepatitis and their clinical characteristics, humoral and pathological, between donors and non- blood donors with antibodies to HCV anti- HCV positive.Methods: t he study group comprised all patients with anti HCV positive, diagnosed byultramicroelisa in Provincial Blood Bank, treated from January ,2000, to December ,2011, in General University Hospital Vladimir Ilich Lenin of Holguin. Liver biopsy was performed to patients. Two intentional samples were selected: patients diagnosed with chronic hepatitisstudy group and control group ,46, donors, 17, non- blood donors without virus surface antigen pretreatment B or interferon and ribavirin Results: chronic hepatitis was higher, P <0.05, in the control group, with more active forms with or without severe fibrosis ,P <0.001, and alaninoaminotransferasas ALAT altere p <0.001, unlike the study group prevalence of hepatitis with mild activity or minimal and normal ALAT. Donors were minority symptomatic difference ,p <0.001, than non- donors,82 percent, with symptoms, in decreasing order: asthenia ,14, right upper quadrant discomfort ,12, and dyspepsia ,7,(AU)...

Efectos adversos del tratamiento con interferón alfa-2b humano recombinante y rivabirina en pacientes con hepatitis crónica C / Adverse effects of treatment with the recombinant human type 2b alpha Interferon and rivabirine in patients presenting with chronic hepatitis C

INTRODUCCIÓN: el tratamiento de la hepatitis crónica C continúa siendo un reto. La combinación que mejores resultados ha demostrado, es la de interferón con ribavirina, pero puede originar efectos adversos con dificultades para la adherencia al tratamiento que en ocasiones, incluso, obligan a suspenderlo. OBJETIVO: identificar las reacciones adversas del tratamiento de la combinación de interferón con ribavirina. MÉTODOS: se realizó un estudio de una serie de 13 pacientes con hepatitis crónica C, atendidos durante los años 2006 y 2007 en consulta especializada del Hospital Universitario Vladimir Ilich Lenin tratados con interferón alfa-2b humano recombinante y ribavirina (Heberviron). RESULTADOS: la fiebre, cefalea, escalofríos, astenia, mialgias y artralgias fueron los efectos adversos más frecuentes, así como síntomas digestivos: anorexia, náuseas, epigastralgia; psíquicos: depresión; hematológicos: anemia y leucopenia. Se observó hipotiroidismo asociado a un cuadro reumatoide en una paciente en la que fue necesario suspender el tratamiento, así como en uno con trombopenia y otro con leucopenia. CONCLUSIONES: al indicar tratamiento con Heberviron al paciente con hepatitis crónica C, hay que tener presente, la frecuencia y magnitud de los efectos secundarios, pues pueden interferir con la adherencia y la respuesta al tratamiento, y ocasionar un impacto negativo en la calidad de vida de los pacientes

INTRODUCTION: The treatment of chronic hepatitis C is still a challenge. The combination with the better results is that of interferon with ribavirin, but it may to create adverse effects including difficulties to follow the treatment which on occasions, even to oblige us to suspend it. OBJECTIVE: To identify the adverse reactions to treatment with the combination of interferon and ribavirin. METHODS: A study was conducted in 13 patients presenting with chronic hepatitis C seen during 2006 and 2007 in the specialized consultation of the "Vladimir Ilich Lenin" University Hospital treated with human recombinant alpha-2b interferon (Heberviron). RESULTS: Fever, headache, chills, asthenia, myalgias and arthralgias were the more frequent adverse effects, as well as digestive symptoms: anorexia, nauseas, epigastralgia and the psychic type: depression, and hematologic type: anemia and leukopenia. Also, there was a hypothyroidism associated with a rheumatoid picture in a patient being necessary to suspend the treatment, as well as in another presenting with thrombopenia and another one with leukopenia. CONCLUSIONS: Prescribing the treatment with Heberviron in the patient with chronic hepatitis C, we must to take into account the frequency and magnitude of side effects, since it may be to interfere with fulfilment of and with the response to treatment and also to create a negative impact in the quality of life of patients

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C / Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

La hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 semanas. RESULTADOS: el 88,5 por ciento del total de casos presentó efectos adversos; de ellos el 79,5 por ciento correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 por ciento de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia

Chronic hepatitis C has reached the category of pandemic. The hepatitis C virus is the main cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplantation worldwide. OBJECTIVE: to identify the side effects of a combined therapy of recombinant interpheron alpha 2b plus ribavirin during the treatment and up to 8 weeks afterwards, as well as the main effects related to temporary or definitive withdrawal. METHODS: a pharmacological surveillance study was performed in which 122 patients with chronic hepatitis C, who had been seen at the Institute of Gastroenterology from May 2001 to May 2006, were included. Recombinant interferon alpha 2b (3 million units administered 3 times a week) plus ribavirin (1 000 or 1 200 mg daily depending on the body weight) was the therapy used for 48 weeks. RESULTS: of the total number of cases, 88,5 percent had side effects; 79,5 percent of which corresponded to pseudocold syndrome followed by hematological, neuropsychiatric and gastrointestinal manifestations, and other less frequent ailments. In the studied group, 6,6 percent had to interrupt their treatment temporarily due to some side effect different from anemia whereas 4 patients gave up the study, three affected by severe hemolytic anemia and one with uncontrollable hyperthyroidism. CONCLUSIONS: the combined therapy of recombinant interferon alpha 2b plus ribavirin proved to be safe; the most frequent side effect was pseudocold syndrome in the majority of cases. The hematological manifestations that made the patients to give up the study led to recommend a strict follow-up of hemoglobin levels and thorough diagnosis and treatment of the main side effects found in other systems and associated to this combined therapy

Efectos adversos del tratamiento con interferón alfa-2b humano recombinante y rivabirina en pacientes con hepatitis crónica C / Adverse effects of treatment with the recombinant human type 2b alpha Interferon and rivabirine in patients presenting with chronic hepatitis C

INTRODUCCIÓN: el tratamiento de la hepatitis crónica C continúa siendo un reto. La combinación que mejores resultados ha demostrado, es la de interferón con ribavirina, pero puede originar efectos adversos con dificultades para la adherencia al tratamiento que en ocasiones, incluso, obligan a suspenderlo. OBJETIVO: identificar las reacciones adversas del tratamiento de la combinación de interferón con ribavirina. MÉTODOS: se realizó un estudio de una serie de 13 pacientes con hepatitis crónica C, atendidos durante los años 2006 y 2007 en consulta especializada del Hospital Universitario Vladimir Ilich Lenin tratados con interferón alfa-2b humano recombinante y ribavirina (Heberviron). RESULTADOS: la fiebre, cefalea, escalofríos, astenia, mialgias y artralgias fueron los efectos adversos más frecuentes, así como síntomas digestivos: anorexia, náuseas, epigastralgia; psíquicos: depresión; hematológicos: anemia y leucopenia. Se observó hipotiroidismo asociado a un cuadro reumatoide en una paciente en la que fue necesario suspender el tratamiento, así como en uno con trombopenia y otro con leucopenia. CONCLUSIONES: al indicar tratamiento con Heberviron al paciente con hepatitis crónica C, hay que tener presente, la frecuencia y magnitud de los efectos secundarios, pues pueden interferir con la adherencia y la respuesta al tratamiento, y ocasionar un impacto negativo en la calidad de vida de los pacientes(AU)

INTRODUCTION: The treatment of chronic hepatitis C is still a challenge. The combination with the better results is that of interferon with ribavirin, but it may to create adverse effects including difficulties to follow the treatment which on occasions, even to oblige us to suspend it. OBJECTIVE: To identify the adverse reactions to treatment with the combination of interferon and ribavirin. METHODS: A study was conducted in 13 patients presenting with chronic hepatitis C seen during 2006 and 2007 in the specialized consultation of the Vladimir Ilich Lenin University Hospital treated with human recombinant alpha-2b interferon (Heberviron). RESULTS: Fever, headache, chills, asthenia, myalgias and arthralgias were the more frequent adverse effects, as well as digestive symptoms: anorexia, nauseas, epigastralgia and the psychic type: depression, and hematologic type: anemia and leukopenia. Also, there was a hypothyroidism associated with a rheumatoid picture in a patient being necessary to suspend the treatment, as well as in another presenting with thrombopenia and another one with leukopenia. CONCLUSIONS: Prescribing the treatment with Heberviron in the patient with chronic hepatitis C, we must to take into account the frequency and magnitude of side effects, since it may be to interfere with fulfilment of and with the response to treatment and also to create a negative impact in the quality of life of patients(AU)

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C / Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

La hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 semanas. RESULTADOS: el 88,5 por ciento del total de casos presentó efectos adversos; de ellos el 79,5 por ciento correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 por ciento de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia(AU)

Chronic hepatitis C has reached the category of pandemic. The hepatitis C virus is the main cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplantation worldwide. OBJECTIVE: to identify the side effects of a combined therapy of recombinant interpheron alpha 2b plus ribavirin during the treatment and up to 8 weeks afterwards, as well as the main effects related to temporary or definitive withdrawal. METHODS: a pharmacological surveillance study was performed in which 122 patients with chronic hepatitis C, who had been seen at the Institute of Gastroenterology from May 2001 to May 2006, were included. Recombinant interferon alpha 2b (3 million units administered 3 times a week) plus ribavirin (1 000 or 1 200 mg daily depending on the body weight) was the therapy used for 48 weeks. RESULTS: of the total number of cases, 88,5 percent had side effects; 79,5 percent of which corresponded to pseudocold syndrome followed by hematological, neuropsychiatric and gastrointestinal manifestations, and other less frequent ailments. In the studied group, 6,6 percent had to interrupt their treatment temporarily due to some side effect different from anemia whereas 4 patients gave up the study, three affected by severe hemolytic anemia and one with uncontrollable hyperthyroidism. CONCLUSIONS: the combined therapy of recombinant interferon alpha 2b plus ribavirin proved to be safe; the most frequent side effect was pseudocold syndrome in the majority of cases. The hematological manifestations that made the patients to give up the study led to recommend a strict follow-up of hemoglobin levels and thorough diagnosis and treatment of the main side effects found in other systems and associated to this combined therapy(AU)

Hepatitis C y diabetes mellitus tipo 2: un estudio prospectivo / Hepatitis C and type 2 diabetes mellitus: a prospective study

Se ha establecido una relación epidemiológica entre hepatitis C crónica (HCV) Y Diabetes Mellitus tipo 2. El objetivo del presente estudio fue determinar de forma prospectiva la prevalencia de Diabetes Mellitus(DM) e intolerancia a la Glucosa en ayunas (IGA) en pacientes con hepatitis C crónica no tratados o naive, en comparación con la población general y con pacientes con enfermedades hepáticas de diferente etiología. Se incluyo una muestra de 13 pacientes que acudieron a la consulta de la Fundación Zuliana del Hígado desde Enero del año 2008 hasta Diciembre del año 2009 en el estudio. La prevalencia de DM e IGA fue de 38% comparado con 8% de la Población general (Centro Venezolano de información y estadística) y 25% del grupo control de 16 pacientes con enfermedades hepáticas de otras etiologías. De los 13 pacientes, cinco fueron Genotipo 1b, uno genotipo 1a y siete Genotipo 2a. De los pacientes con DM o IGA, dos fueron Genotipo 1b, uno 1a y dos 2a. De los cinco pacientes con DM o IGA cuatro tenían antecedente familiares de Diabetes. En conclusión, pacientes con HCV crónica tienen una mayor prevalencia de DM e IGA en comparación con la población general y con pacientes afectados por enfermedades hepáticas de otra etiología. El Genotipo no tuvo relación en este estudio con la DM o la IGA; los marcadores antropométricos de Obesidad estuvieron asociados en tres de los cinco pacientes lo cual sumado a la historia familiar de Diabetes siguiere una relación multifactorial en la patogénesis de la DM en los pacientes con HCV.

An epidemiologic link between chronic Hepatitis C (HCV) and Type 2 Diabetes mellitus (DM) has been established. The objective of the present study was to prospectively determine the prevalence of Diabetes Mellitus (DM) and impaired fasting glucose (IFG) in patients with hepatitis C not treated or naive, in comparison with the general population and patients with other hepatic diseases. A sample of 13 patients who went to the outpatient clinic of the Zuliana Foundation of the Liver, from January of year 2008 to December of year 2009 was included in the study. The prevalence of DM and IGA was of 38% compared with 8% of the general Population (Center Venezuelan of information and statistic) and 25% of the group control of 16 patients with other hepatic diseases. Of 13 patients five were Genotype 1b, one genotype 1a and seven Genotype 2a. Of the patients with DM or IGA, two were Genotype 1b, one 1a and two 2a. Of the five patients with DM or IGA four had family history of Diabetes. In conclusion, patients with chronic HCV have a greater prevalence of DM and IGA in comparison with the general population and patients affected by different hepatics diseases. There was not relation in this study between the Genotype with the DM or the IGA; the anthropomorphic markers of Obesity were associated in three of the five patients, which added to the familiar history of Diabetes will follow a multifactorial relation in the pathogenesis of the DM in the patients with HCV.

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad(AU)

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease(AU)

Tratamiento de la hepatitis crónica por virus C con interferón pegilado cubano y ribavirina / Treatment of chronic hepatitis C with Cuban pegylated interferon and ribavirin

Introducción: es en la actualidad la asociación de interferón pegilado y ribavirina la terapia más aceptada internacionalmente para el tratamiento de la hepatitis crónica C. En el 2011 comienza la aplicación en Matanzas de dicha combinación, utilizándose el interferón pegilado cubano (PEG-Heberon), con el cual se abrió un nuevo camino en el manejo terapéutico de esta enfermedad. Objetivo: describir los primeros resultados en Matanzas de la aplicación del PEG-Heberon y la ribavirina en el tratamiento de la hepatitis crónica C. Métodos: estudio descriptivo-prospectivo. Universo, 19 pacientes procedentes de la Consulta Provincial de Hepatología del Hospital Universitario Clínico Qurúrgico Comandante Faustino Pérez. Las variables estudiadas fueron: sexo, grupo etáreo, tipo de paciente, forma de presentación, efectos adversos, conducta ante estos, respuestas bioquímica y virológica al tratamiento.Resultados: predominaron los pacientes del sexo femenino (57,9 por ciento), edad promedio de 41,7 ± 9,2 años, vírgenes de tratamiento (73,7 por ciento) y con forma clínica asintomática (68,4 por ciento). Se registraron efectos adversos en el 100 por ciento de los casos, todos los clínicos fueron leves y entre los hematológicos el 70,4 por ciento resultaron leves. No se reportaron eventos graves ni suspensiones del tratamiento. Se obtuvo respuesta bioquímica al concluir tratamiento en el 89,4 por ciento y sostenida en el 78,9 por ciento. La virológica se logró en el 78,9 por cientoal término del tratamiento y en el 68,4 por ciento seis meses después de este. Conclusión: se logró una elevada adherencia a la terapia combinada resultando tolerada y segura para los pacientes con tasas aceptables de respuesta virológica sostenida (RVS)(AU)

Introduction: currently, the association of pegylated interferon and ribavirin is internationally the most accepted therapy for the treatment of chronic hepatitis C. The application of this combination began in Matanzas in 2011, using the Cuban pegylated interferon (PEG-Heberon), setting up a new way in the therapeutic management of this disease. Objective: to describe the first results of the PEG-Heberon and ribavirin application in the treatment of chronic hepatitis C in Matanzas. Methods: descriptive- prospective study. Universe: 19 patients from the provincial consultation of Hepatology of the University Clinic-surgical Hospital Comandante Faustino Pérez in the period from October 2011 to October 2013. The studied variables were: sex, age groups, type of patient, presentation way, adverse reactions, behavior against them, biochemical and virologic answers to treatment.Results: there it was a predominance of female patients (57,9 percent); the average age was 41,7 ± 9,2 years; treatment-virgins (73,7 percent) and asymptomatic clinical forms (68,4 percent). There were adverse reactions in 100 percent of the cases; all the clinical ones were mild and among the hematologic ones, 70,4 percent were light. There were neither serious events nor cancelations of the treatment. There was a biochemical answer at the end of the treatment in 89,4 percent and a maintained one in 78,9 percent. The virological answer was achieved at the end of the treatment in 78,9 percent, and six months after treatment in 68,4 percent of the patients. Conclusion: a high adherence to the combined therapy was achieved, being tolerated and safe for the patient, with acceptable rates of continuous virological answers(AU)