Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan / Recorrência do vírus da hepatite C após tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Embora aumentem as taxas de resposta concomitantes no vírus da hepatite C (HCV), há risco de recidiva após o tratamento. Portanto, é um requisito terrível avaliar a resposta do interferon peguilado e antivirais de ação direta em Punjab, Paquistão. O estudo foi conduzido para encontrar a taxa de recorrência da infecção por HCV após o tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão. Este estudo foi conduzido no Departamento de Patologia Nawaz Sharif Medical College Gujrat, enquanto os efeitos do tratamento foram monitorados em diferentes hospitais públicos e privados de Punjab, Paquistão. Total de 973 pacientes que administraram a dose recomendada foram divididos em dois grupos: (i) Terapia baseada em interferon, (ii) antivirais de ação direta (DAAs). Outros parâmetros como ALT e carga viral foram estudados. A taxa de recorrência foi maior em mulheres infectadas com o genótipo 2b e em homens com genótipo misto 3a / 2b após seis meses de terapia antiviral. O genótipo 3a mostrou resposta significativa à terapia após três meses. 32 entre 374 (8,5%) foram positivos após 24 semanas de tratamento com interferon, 29 (7,7%) pacientes têm o mesmo genótipo, enquanto 3 pacientes foram reinfectados com diferentes cepas de HCV. Com DAAs, apenas 27 (4,8%) pacientes foram positivos entre 558 após duas semanas e um paciente reinfectado com genótipo diferente. Resposta virológica precoce e sustentada observada em DAAs. ALT e carga viral diminuíram mais rapidamente com DAAs, que não alcançou após 4 semanas com interferon peguilado. A resposta virológica sustentada aparece em DAAs, e a taxa de recorrência é alta na terapia com interferon em comparação com DAAs. Portanto, a reinfecção tem implicações para a eficiência do tratamento correto e para selecionar estratégias para casos de retratamento.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Efectividad y seguridad de sorafenib en pacientes con cáncer renal de células claras, metastásico, sin respuesta a inhibidores de tirosin-quinasa o citoquinas (interleuquina o interferón), riesgo bajo-intermedio / Effectiveness and safety of sorafenib in patients with clear-cell, metastatic renal cancer without response to tyrosine kinase inhibitors or cytokines (interleukin or interferon), low-intermediate risk

Introducción: en el mundo, en relación con la frecuencia de todos de cánceres de cualquier localización, el cáncer renal se encuentra dentro de los diez más frecuentes en hombres y el catorceavo en mujeres (1). Existen varias opciones terapéuticas de segunda línea en aquellos pacientes con cáncer renal avanzado o metastásico, sin respuesta a inhibidores de tirosina-quinasa o citoquinas, que pueden incluir medicamentos como: Inhibidores de mTOR (Temsirolimus, everolimus), inhibidores de tirosinquinasa (Sunitinib, sorafenib, pazopanib, axitinib), y otros inhibidores de la angiogénesis como bevacizumab. Dadas las opciones planteadas se hace necesario conocer la efectividad y la seguridad de estas intervenciones. Objetivo: examinar los beneficios y riesgos del uso de sorafenib como uno de los criterios para informar la toma de decisiones relacionada con la posible inclusión de tecnologías en el Plan Obligatorio de Salud, en el marco de su actualización ordinaria para el año 2015. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, LILACS y Google, sin restricciones de idioma, fecha de publicación y tipo de estudio. Las búsquedas electrónicas fueron hechas en noviembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad predefinidos. Las características y hallazgos de los estudios fueron extraídos a partir de las publicaciones originales. Resultados: Efectividad existe mejoría significativa para el desenlace de supervivencia libre de progresión a favor de sorafenib comparado con placebo, con un HR 0,44 (IC 95 % 0,35-0,55; I2 11%) mediante comparación indirecta; se reportó mejoría significativa para el desenlace de supervivencia libre de progresión a favor de sunitinib comparado con sorafenib, con un HR 1,63 (IC 95% 1,09- 2,45); mejoría significativa para el desenlace de supervivencia libre de progresión a favor de axitinib comparado con sorafenib, con un HR 0,67 (IC 95% 0,54- 0,81). Seguridad: mediante comparación indirecta, reportó que el axitinib disminuye del 45% del abandono de terapia secundaria a eventos adversos cuando se compara con sorafenib (IC 95% 0,24-0,84). No se encontraron diferencias estadísticamente significativas para los desenlaces de: abandono de terapia y diarrea. Para el desenlace de fatiga se presenta un incremento del riesgo con axitinib comparado con sorafenib, RR 2,30 (IC 95% 1,34-4,10). Sorafenib incrementa el riesgo de reacción cutánea mano-pie comparado con axitinib, RR 0,31 (IC 95% 0,17-0,52), así como, incremento del riesgo de rash, RR 0,10 (IC 95% 0,02-0,41) en la misma comparación. El axitinib incrementa el riesgo de estomatitis RR 8,1 (IC 95% 1,1->100). Conclusiones: efectividad: Sorafenib presenta mejoría significativa en la supervivencia libre de progresión cuando se compara con placebo. Al comparar de manera indirecta sorafenib con otros agentes como axitinib y sunitinib, se reportó mejoría de la supervivencia libre de progresión significativa clínicamente a favor de axitinib y sunitinib. No se reportaron desenlaces de efectividad clínicamente significativos con otros agentes como: pazopanib, everolimus, temsirolimus. En esta revisión no se identificó evidencia que cumpliera con los criterios de inclusión y que comparara sorafenib con bevacizumab, ni evidencia que reporte los desenlaces de supervivencia global y calidad de vida. Seguridad: En relación con la seguridad del tratamiento de segunda línea con sorafenib se evidencia de manera general un aumento del riesgo de presentar eventos adversos grado III/IV. Al evaluar el desenlace de abandono de terapia secundaria a eventos adversos se evidencia que sorafenib aumentó el riesgo, comparado con axitinib. Para el desenlace de reacción cutánea mano-pie el uso de sorafenib presenta aumento del riesgo comparado con placebo, pazopanib, axitinib y everolimus. Sorafenib reporta aumento de riesgo de presentar rash comparado con axitinib, así como, de diarrea cuando se compara con placebo. En esta revisión no se identificó evidencia que cumpliera con los criterios de elegibilidad y que comparara sorafenib con bevacizumab.(AU)

Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

Interferones lambdas (IFNs-lambda) en infección con virus hepatitis C / Lamba interferons in infection with hepatitis C virus

The current standard therapy for patients chronically infected with hepatitis C virus (HCV) is the administration of pegylated interferon-alpha (PEG-IFN) plus ribavirin (RBV), eliminating the virus in only about half of patients infected with the genotype most common in Chile and the world (genotype 1), being higher for genotypes 2 and 3. Genotyping of the HCV is a strong predictor of treatment response, and it defines the treatment duration (48 weeks for genotype 1 and 24weeks for genotypes 2 and 3). Genome studies revealed the association of polymorphisms (SNPs) close to IL28B gene with increased spontaneous and treatment-inducing clearance for HCV, which are now evaluated as a strong predictor of treatment response. These SNPs are close to genes coding for type III IFNs family, known as IFNs lambda (IFNs lambda), composed by IFN lambda1 (IL29), IFN lambda2 (IL28A) and IFN lambda3 (IL28B). It has been shown that these cytokines are highly involved in antiviral immune responses, including HCV, playing IFN lambda1 a central role. Today, there is an ongoing study where pegylated IFN alpha1 was administrated in chronic HCV patients as alternative to IFN lambda therapy, seeking for a more specific response to infected hepatocytes and with fewer adverse effects.

Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon

BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.

Extended treatment with interferon and ribavirin in a hemodialysis patient with chronic hepatitis C

Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.

Chronic hepatitis C: hepatic iron content does not correlate with response to antiviral therapy / Hepatite C crônica: concentração hepática de ferro não é correlacionada com a resposta ao tratamento antiviral

The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.

A complexa interação entre infecção pelo vírus da hepatite C, homeostase do ferro e resposta ao tratamento antiviral permanece controversa. O objetivo deste estudo foi avaliar a influência da concentração hepática de ferro (CHF) na resposta virológica sustentada (RVS) à terapia antiviral na hepatite C crônica. Foram incluídos 50 pacientes que foram submetidos à biopsia hepática pré-tratamento com determinação da CHF por espectrofotometria de absorção atômica com forno de grafite e tratados posteriormente com interferon/peginterferon e ribavirina. Pacientes com alcoolismo, história de múltiplas transfusões sanguíneas, doença renal crônica, anemia hemolítica e terapia com ferro parenteral foram excluídos. O perfil de ferro sérico e a CHF foram comparados entre aqueles que atingiram RVS e os não-respondedores (NR). A média de idade dos pacientes foi 45,7 anos e não houve diferença na proporção de homens e mulheres entre os grupos RVS e NR. A mediana do ferro sérico foi 138 and 134 µg/dL (p = 0.9), a mediana da ferritina sérica foi 152,5 e 179,5 ng/mL (p = 0,87) e a CHF mediana foi 9,9 e 8,2 µmol/g de tecido seco (p = 0,51), para pacientes com RVS e NR, respectivamente. Concluindo, a concentração hepática de ferro, determinada por um método quantitativo confiável, não foi um fator preditivo negativo de RVS em pacientes com hepatite C crônica e acúmulo de ferro hepático leve a moderado.

Histological response study of chronic viral hepatitis C patients treated with interferon alone or combined with ribavirin

Chronic hepatitis C is often a progressive, fibrotic disease that can lead to cirrhosis and other complications. The recommended therapy is a combination of interferon and ribavirin. Besides its antiviral action, interferon is considered to have antifibrotic activity. We examined the outcome of hepatic fibrosis and inflammation in chronic hepatitis C patients who were non-responders to interferon. We made a case series, retrospective study, based on revision of medical records and reassessment of liver biopsies. For inclusion, patients should have been treated with interferon alone or combined with ribavirin, with no virological response (non responders and relapsers) and had a liver biopsy before and after treatment. Histological evaluation included: i-outcome of fibrosis and necroinflammation; ii-annual fibrosis progression rate evaluation, before and after treatment. Seventy-five patients were included. Fifty-seven patients (76 percent) did not show progression of fibrosis after treatment, compared to six (8 percent) before treatment (p < 0.001). The mean annual fibrosis progression rate was significantly reduced after treatment (p = 0.036). Inflammatory activity improved in 19 patients (25.3 percent). The results support the hypothesis of an antifibrotic effect of interferon-based therapy, in non-responder patients. There was evidence of anti-inflammatory effects of treatment in some patients.

Secreción de interferon por los linfocitos T periféricos de los portadores crónicos del virus de hepatitis B / Interferon G secretion by the peripheral lymphocyts T of the chronic carries of the hepatitis B virus

Previamente demostramos que los linfocitos T periféricos de los portadores crónicos del VHB activados “in vitro” con fitohemaglutinina (PHA) o con anticuerpos monoclonales anti-CD3 secretan interleucina-2 (IL-2) y expresan receptores para IL-2, IL-6 y para el factor de necrosis tumoral. Investigamos la producción de interferón por células T altamente purificadas (98 por ciento CD3+) de 14 pacientes infectados crónicamente por el VHB. Los linfocitos T se activaron con PHA sola (0.5g/mL) y con PHA añadiendo 100 L de sobrenadantes de monocitos (SMo) obtenidos después de la activación de los monocitos autólogos y alogénicos con lipopolisacárido. Los linfocitos T estimulados con PHA de los pacientes infectados por el VHB secretaron interferón en forma similar a los controles (438+129 vs. 577+127 pg/mL). En presencia de PHA más SMo autólogos, los linfocitos T de los pacientes no sufrieron modificación en la secreción de interferon, siendo la misma significativamente menor a la demostrada por las células T de los controles cultivadas en iguales condiciones (589+124 vs. 922+121 pg/mL; p<0.05). Al adicionar SMo alogénicos (PHA + SMo de controles), los linfocitos T de los portadores crónicos del VHB incrementaron la producción de interferón a una concentración significativamente mayor a la obtenida en presencia de PHA sola (752+123 vs. 438+129 pg/mL; p<0.01). En conclusión, los linfocitos T periféricos de los portadores crónicos del VHB son capaces de secretar interferón y responden incrementando esta secreción cuando son expuestos a factores solubles de monocitos alogénicos lo que indica que esta población celular T preserva su habilidad funcional para mediar respuestas inmunes

Caffeine clearance in patients with chronic viral hepatitis: before and after interferon therapy.

The purpose of this study was to evaluate caffeine clearance, a quantitative measurement of metabolizing capacity of the liver, in chronic hepatitis B and C before and after interferon treatment. Biochemical test using AST and ALT, virological test, and caffeine clearance were measured in eighteen patients with chronic hepatitis B and five patients with chronic hepatitis C at pre and post treatment with interferon. Caffeine clearance was determined in each patient using two point analysis following a 3.5 mg/kg oral administration of caffeine solution. Blood samples were subsequently collected at 12 and 16 hours after caffeine administration and assayed for serum caffeine level by HPLC technique. Clearance was calculated using the equation of Cl = Kel x Vd. It was found that caffeine clearances determined before and after interferon treatment were not significantly different in both chronic hepatitis B and C inspite of biochemical and virological responses after therapy. Caffeine clearance change in two diffferent groups of chronic hepatitis B defined as biochemical response and nonresponse were compared. Although caffeine clearance change between responders and nonresponders to interferon treatment was not significantly different, it tended to increase in those patients who had biochemical response to interferon. It appeared that metabolic capacity of the liver does not change with interferon therapy inspite of biochemical and virological responses.

O monitoramento de pacientes recebendo interleucina e interferon: bases fármaco-clínicas para a assistência de enfermagem / Interleukins and interferons: nursing care

Mediante as novas associaçöes de drogas que combinam quimioterápicos convencionais e modificadores da resposta biológica: interleucinas (IL) e interferons (INF), para o tratamento de neoplasias pouco responsivas aos esquemas convencionais, buscamos na literatura diretrizes para a manipulaçäo e administraçäo adequadas dessas drogas, e subsídios para a avaliaçäo clínica de enfermagem, considerando os mecanismos de açäo das drogas e os principais efeitos colaterais, bem como consideraçöes para a orientaçäo do paciente/familiar quanto aos cuidados diante do tratamento hospitalar ou ambulatorial.

An open trial of long-term interferon therapy for chronic hepatitis C: appraisal of serum HCV RNA and the influence of HCV genotypes in the response

Evaluar la efectividad y el resultado del tratamiento con interferón-alfa-2b por un período de 12 meses en los niveles séricos de las aminotransferasas y del rol de los genotipos en la hepatitis crónica C. Fueron evaluados 38 pacientes de nuestra consulta con hepatitis crónica anti-HCV positivos. Todos los pacientes tenían infección por HCV, excluyendo otras causas de enfermedad crónica del hígado. El ARN-HCV fue realizado en 34 pacientes por la técnica de transcripción reversa. El HCV genotipo fue estudiado por RFLP en 18 pacientes. Tres pacientes fueron excluidos por reacciones adversas (7,8 por ciento). Treinta y cinco fueron seguidos por un período de 6 a 12 meses después de haber completado el tratamiento. Se observó una respuesta completa en 15 pacientes (39,4 por ciento). Una respuesta sostenida fué obtenida en 10 pacientes (26,3 por ciento). La respuesta sostenida fué significativa en pacientes jóvenes comparado con el otro grupo (no respondedores y los que recayeron) (p:0.001). La proporción de pacientes con respuesta sostenida fué mayor en pacientes que tenían otros genotipos que no fueran el 1b (p:0.0036). En el 70,0 por ciento de los pacientes con respuesta sostenida el ARN-HCV se negativizó, sin embargo, el 30 por ciento restante tenía viremia residual. Este estudio sugiere que el tratamiento por 12 meses con interferón-alfa-2b es un régimen terapéutico valioso para pacientes con hepatitis crónica C. Existe una gran probabilidad de obtener un buen resultado a largo plazo de curar la infección por HCV cuando los pacientes logran normalizar las aminotransferasas y negativizar el ARN-HCV en los tres primeros meses de tratamiento. Los HCV genotipos tienen una gran significación pronóstica en relación con el tratamiento con interferón-alfa-2b. Una respueta sostenida es observada generalmente cuando los pacientes tienen otros genotipos que no sean el 1b