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Rev. Soc. Bras. Med. Trop ; 51(2): 146-154, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897067


Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Humans , Male , Female , Adult , Aged , Antiviral Agents/administration & dosage , Protease Inhibitors/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Oligopeptides/administration & dosage , Oligopeptides/adverse effects , Antiviral Agents/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Protease Inhibitors/adverse effects , Ribavirin/administration & dosage , Ribavirin/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Proline/administration & dosage , Proline/analogs & derivatives , Proline/adverse effects , Retrospective Studies , Treatment Outcome , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Hepacivirus/drug effects , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions , Interferon alpha-2 , Genotype , Middle Aged
Rev. Assoc. Med. Bras. (1992) ; 63(12): 1061-1064, Dec. 2017. tab
Article in English | LILACS | ID: biblio-896326


Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF) injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05). In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.

Humans , Male , Female , Adult , Aged , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/adverse effects , Colonic Neoplasms/drug therapy , Chemotherapy-Induced Febrile Neutropenia/prevention & control , Antineoplastic Agents/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Treatment Outcome , Injections , Middle Aged
Rev. méd. Chile ; 145(6): 710-715, June 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-902535


Background: Extracorporeal membrane oxygenation (ECMO) is used with increasing frequency in patients with respiratory and cardiac failure. The achievement of an adequate anticoagulation is critical to avoid patient and circuit complications. Aim: To assess the feasibility and safety of anticoagulation with bivalirudin, as an alternative to unfractionated heparin (UFH), in patient with ECMO. Material and Methods: Observational study, which included all patients receiving anticoagulation with bivalirudin during ECMO, according to a standardized protocol, between august 2015 to May 2016. Results: Bivalirudin was used in 13 out 70 patients connected to ECMO. Ten procedures were for cardiac support and three for respiratory support. Mortality was 43%. ECMO lasted 31 ± 31 days. The time of UFH use before changing to bivalirudin was 7 ± 7 days. The reasons to change to bivalirudin were inadequate levels of partial thromboplastin time (PTT) in nine patients, and heparin induced thrombocytopenia (HIT) in four patients. The time of bivalirudin use was 24 ± 33 days. Per patient, a mean of 2.7 ± 4 oxygenators were changed. These had a useful life of 11.4 and 19.1 days during UFH and bivalirudin use, respectively. The mean bivalirudin dose was 0.08 ± 0.04 mg/kg/h. There was no significant bleeding, thrombosis or circuit obstruction during its use. PTT levels (p < 0.01) and platelet count (p < 0.01) increased significantly after the start of bivalirudin use in patients with UHF resistance and HIT, respectively. Conclusions: Bivalirudin was a safe and efficient drug for anticoagulation during ECMO. It is important to have an alternative drug for anticoagulation in ECMO patients.

Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Young Adult , Peptide Fragments/blood , Extracorporeal Membrane Oxygenation , Hirudins/blood , Anticoagulants/blood , Partial Thromboplastin Time , Peptide Fragments/administration & dosage , Platelet Count , Recombinant Proteins/administration & dosage , Recombinant Proteins/blood , Heparin/adverse effects , Feasibility Studies , Hirudins/administration & dosage , Anticoagulants/administration & dosage
Clinics ; 72(6): 378-385, June 2017. tab, graf
Article in English | LILACS | ID: biblio-840088


OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Humans , Male , Female , Middle Aged , Aged , Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/administration & dosage , Brazil , Cross-Sectional Studies , Genotype , Hepatitis C, Chronic/virology , Interferon-alpha/administration & dosage , Oligopeptides/administration & dosage , Polyethylene Glycols/administration & dosage , Proline/administration & dosage , Proline/analogs & derivatives , Recombinant Proteins/administration & dosage , RNA, Viral/genetics , Treatment Outcome
Rev. bras. cir. cardiovasc ; 32(2): 96-103, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-843481


Abstract INTRODUCTION: The mortality due to cardiogenic shock complicating acute myocardial infarction (AMI) is high even in patients with early revascularization. Infusion of low dose recombinant human brain natriuretic peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac function. OBJECTIVE: The objective of this study was to evaluate the hemodynamic effects of rhBNP in AMI patients revascularized by emergency percutaneous coronary intervention (PCI) who developed cardiogenic shock. METHODS: A total of 48 patients with acute ST segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and whose hemodynamic status was improved following emergency PCI were enrolled. Patients were randomly assigned to rhBNP (n=25) and control (n=23) groups. In addition to standard therapy, study group individuals received rhBNP by continuous infusion at 0.005 µg kg−1 min−1 for 72 hours. RESULTS: Baseline characteristics, medications, and peak of cardiac troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in consistently improved pulmonary capillary wedge pressure (PCWP) compared to the control group. Respectively, 7 and 9 patients died in experimental and control groups. No drug-related serious adverse events occurred in either group. CONCLUSION: When added to standard care in stable patients with cardiogenic shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well tolerated.

Humans , Male , Female , Middle Aged , Aged , Natriuretic Peptide, Brain/administration & dosage , Anterior Wall Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention/mortality , ST Elevation Myocardial Infarction/drug therapy , Shock, Cardiogenic/etiology , Blood Pressure/drug effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Pulmonary Wedge Pressure/drug effects , Analysis of Variance , Natriuretic Peptide, Brain/therapeutic use , Natriuretic Peptide, Brain/pharmacology , Anterior Wall Myocardial Infarction/complications , Anterior Wall Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/mortality , Heart Rate/drug effects , Intra-Aortic Balloon Pumping/methods
Rev. bras. parasitol. vet ; 26(1): 67-73, Jan.-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-844125


Abstract The aim of the present study was to evaluate oocyst shedding in cats immunized by nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus) were divided in three groups G1, G2 and G3 (n=4). Animals from G1 received 100 μg of rROP2 proteins plus 20 μg of Quil-A, G2 received 100 μg of BSA plus 20 μg of Quil-A, and the G3 only saline solution (control group). All treatments were done by intranasal route at days 0, 21, 42, and 63. The challenge was performed in all groups on day 70 with ≅ 800 tissue cysts of ME-49 strain by oral route. Animals from G1 shed less oocysts (86.7%) than control groups. ELISA was used to detect anti-rROP2 IgG and IgA, however, there were no correlation between number of oocyst shedding by either IgG or IgA antibody levels. In the present work, in spite of lesser oocysts production in immunized group than control groups, it was not possible to associate the use of rROP2 via nostrils with protection against oocyst shedding. For the future, the use of either other recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to try improving the efficacy of this kind of vaccine.

Resumo O objetivo do presente estudo foi avaliar a eliminação de oocistos de Toxoplasma gondii em gatos imunizados pela via nasal com proteínas ROP2 de T. gondii. Doze gatos sem raça definida (Felis catus) foram divididos em três grupos experimentais G1, G2 e G3 (n = 4). Os animais do G1 receberam 100 μg de proteínas de rROP2 mais 20 μg de Quil-A, G2 recebeu 100 μg de albumina de soro bovino (BSA) junto com 20 μg de Quil-A, e o G3 recebeu apenas solução salina (grupo de controle). Todos os tratamentos foram realizados pela via intranasal nos dias 0, 21, 42 e 63. O desafio foi realizado em todos os grupos no dia 70 com aproximadamente 800 cistos de tecido da cepa ME-49 por via oral. Os animais de todos os grupos tiveram as suas fezes examinadas e o número de oocistos foi determinado durante 20 dias após o desafio. Os animais de G1 eliminaram menos oocistos (86,7%) do que os grupos controles. O ELISA foi utilizado para detectar IgG e IgA anti-rROP2, no entanto, não houve correlação entre o número de eliminhação de oocistos com os níveis de anticorpos IgG ou IgA. No presente trabalho, apesar da menor produção de oocistos no grupo imunizado (G1) em relação aos grupos controles (G2 e G3), não foi possível associar o uso de rROP2 pela via nasal com proteção contra eliminação de oocistos de T. gondii. Para o futuro, a utilização de outras proteínas recombinantes, ou mesmo vacina de DNA, em combinação com rROP2 poderia ser utilizada para tentar melhorar a eficácia deste tipo de vacina.

Animals , Cats , Cat Diseases/prevention & control , Protozoan Proteins/immunology , Toxoplasmosis, Animal/prevention & control , Protozoan Vaccines/immunology , Membrane Proteins/immunology , Toxoplasma/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Administration, Intranasal , Antibodies, Protozoan , Cat Diseases/immunology , Protozoan Proteins/administration & dosage , Toxoplasmosis, Animal/immunology , Adjuvants, Immunologic/administration & dosage , Protozoan Vaccines/administration & dosage , Oocysts/immunology , Quillaja Saponins/administration & dosage , Quillaja Saponins/immunology , Membrane Proteins/administration & dosage
Braz. oral res. (Online) ; 31: e99, 2017. tab, graf
Article in English | LILACS | ID: biblio-952129


Abstract The aim of the present study was to evaluate the possible use of a commercial absorbed collagen sponge and bone morphogenetic protein (BMP) for the prevention of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in rats. Twenty rats received intraperitoneal injections of 0.1-mg/kg of zoledronic acid three times a week for eight weeks before the extraction of both maxillary first molars after eight weeks. A collagen sponge (experimental group 1) and a collagen sponge with recombinant human BMP-2 (experimental group 2) were applied to the right extraction sockets of ten rats each. The 20 left extraction sockets (control groups 1 and 2) were left unprotected. After eight weeks, all rats were euthanized. Macroscopic analysis, micro-computed tomography (CT) analysis, and histological analysis were performed. There was a significant difference in the bone density between the control and experimental groups on micro-CT analysis. Impaired healing of the extraction sockets, indicating BRONJ, was observed in 80% of control group 1, 90% of control group 2, 30% of experimental group 1, and 20% of experimental group 2. The collagen sponge with/without BMP used for protecting the extraction socket had the potential for a positive effect in reducing the incidence of bisphosphonate-related osteonecrosis of the jaw in rats.

Animals , Female , Rats , Wound Healing/drug effects , Surgical Sponges , Transforming Growth Factor beta/administration & dosage , Collagen/administration & dosage , Tooth Socket/drug effects , Diphosphonates/pharmacology , Bone Morphogenetic Protein 2/administration & dosage , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Imidazoles/pharmacology , Recombinant Proteins/administration & dosage , Rats, Sprague-Dawley , X-Ray Microtomography , Zoledronic Acid
Rev. chil. pediatr ; 88(1): 119-127, 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-844589


El retraso del crecimiento de los niños con enfermedad renal crónica es de origen multifactorial, incluyendo la resistencia a hormona de crecimiento (GH) y alteraciones en el metabolismo mineral óseo. Objetivos: 1) Caracterizar marcadores del metabolismo mineral: FGF23-Klotho y del eje somatotrópico: IGF1, IGFBP3 y GHBP, en niños en diálisis peritoneal (DP); 2) Evaluar la evolución de la talla en aquellos pacientes tratados con rhGH. Pacientes y Método: Niños prepuberales en DP seguidos durante 12 meses. Criterios exclusión fueron Tanner > 1, síndrome nefrótico activo, tratamiento esteroidal, malabsorción gastrointestinal, enfermedades endocrinas, síndromes genéticos, uso de rhGH al ingreso del estudio. Se evaluaron variables demográficas, antropométricas: Z talla/edad, (ZT/E), velocidad de crecimiento (VC), bioquímicas (calcio, fósforo, PTH), marcadores del metabolismo mineral (25OHvitD, 1,25OHvitD, FGF23, Klotho), y de crecimiento (IGF-1, IGFBP-3, GHBP). Resultados: Quince pacientes, 7 varones, edad 6,9 ± 3,0 años, tiempo en DP 14,33 ± 12,26 meses. Puntaje ZT/E al mes 1= -1,69 ± 1,03. FGF23: 131,7 ± 279,4 y Klotho: 125,9 ± 24,2 pg/ml. Durante los 12 meses de seguimiento no hubo diferencia significativa en el promedio de las variables. El uso de rhGH en 8 pacientes no mostró mejoría significativa del ZT/E ni la VC. El análisis bivariado mostró correlación positiva entre niveles de Klotho y delta ZT/E, y entre GHBP y VC (p < 0,05). Conclusiones: Los valores de FGF23 se encuentran elevados y los de Klotho disminuidos en niños con enfermedad renal crónica en DP en comparación con niños sanos. Las variables de eje somatotrópico, se encuentran normales o elevadas. rhGH tiende a mejorar la talla y GHBP se correlaciona positivamente con VC en estos niños.

Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. Objectives: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. Patients and Method: A longitudinal 12-month follow-up in prepuberal PD children. Exclusion criteria: Tanner stage >1, nephrotic syndrome, genetic disorders, steroids, intestinal absorption disorders, endocrine disturbances, treatment with GH to the entry of the study. Demographic and anthropometric data were registered. FGF23, Klotho, VitD, IGF-1, IGFBP3, and GHBP were measured to evaluate mineral and growth metabolism. Results: 15 patients, 7 male, age 6.9 ± 3.0 y were included. Time on PD was 14.33 ± 12.26 months. Height/age Z score at month 1 was -1.69 ± 1.03. FGF23 and Klotho: 131.7 ± 279.4 y 125.9 ± 24.2 pg/ml, respectively. 8 patients were treated with GH during 6-12 months, showing a non-significant increase in height/age Z-score during the treatment period. Bivariate analysis showed a positive correlation between Klotho and delta ZT/E, and between GHBP vs growth velocity index (p < .05). Conclusions: FGF23 values were high and Klotho values were reduced in children with CKD in PD, comparing to healthy children. Somatotropic axis variables were normal or elevated. rhGH tends to improve height and there is a positive correlation of GHBP and growth velocity in these children.

Humans , Male , Female , Child, Preschool , Child , Peritoneal Dialysis/methods , Human Growth Hormone/administration & dosage , Growth Disorders/etiology , Minerals/metabolism , Time Factors , Body Height/drug effects , Recombinant Proteins/administration & dosage , Bone Density/drug effects , Case-Control Studies , Prospective Studies , Follow-Up Studies , Longitudinal Studies , Human Growth Hormone/metabolism , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Growth Disorders/drug therapy
Braz. j. med. biol. res ; 49(7): e5300, 2016. tab, graf
Article in English | LILACS | ID: lil-785056


The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.

Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Anemia/etiology , Hepatitis C, Chronic/drug therapy , Oligopeptides/administration & dosage , Proline/analogs & derivatives , Protease Inhibitors/administration & dosage , Antiviral Agents/administration & dosage , Glomerular Filtration Rate , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Interferon-alpha/administration & dosage , Logistic Models , Oligopeptides/adverse effects , Polyethylene Glycols/administration & dosage , Proline/administration & dosage , Proline/adverse effects , Prospective Studies , Protease Inhibitors/adverse effects , Recombinant Proteins/administration & dosage , Ribavirin/administration & dosage , Risk Factors , Severity of Illness Index , Statistics, Nonparametric , Sustained Virologic Response , Time Factors , Treatment Failure
Rev. Esc. Enferm. USP ; 49(6): 937-943, Dec. 2015. graf
Article in Portuguese | LILACS, BDENF | ID: lil-767809


Abstract OBJECTIVE Comparing Health-Related Quality of Life (HRQoL) scores in patients with chronic hepatitis C undergoing double and triple antiviral therapy and analyzing possible factors related to HRQoL. METHOD HRQoL was assessed using the Short Form 36 and Chronic Liver Disease Questionnaire, which were applied at baseline and at weeks 4, 12 and 16 of treatment to 32 patients divided into two groups: double therapy with pegylated interferon (IFN-PEG) and ribavirin, and triple therapy with PEG-IFN, ribavirin and telaprevir. RESULTS The reduction of HRQoL was greater in patients receiving triple therapy compared to those treated with two drugs, the most critical time is at 12 weeks in both groups. After removal of telaprevir, the triple therapy group significantly improved their HRQoL scores. Anxiety and depression before treatment, employment status and race are significantly related to diminished HRQoL. CONCLUSION Patients undergoing double and triple therapy have diminished HRQoL indexes, but the addition of telaprevir chooses a more significant decrease.

Resumen OBJETIVO Comparar los puntajes de Calidad de Vida Relacionada con la Salud (CVRS) en pacientes con hepatitis C crónica sometidos a la terapia antiviral doble y triple y analizar los posibles factores relacionados con la CVRS. MÉTODO La CVRS fue evaluada utilizando el Short Form 36 y elChronic Liver Disease Questionnaire , que fueron aplicados antes y en las semanas 4, 12 y 16 de tratamiento, en 32 pacientes divididos en 2 grupos: terapia doble con interferón pegilado (IFN-PEG) y ribavirina, y triple con IFN-PEG, ribavirina y telaprevir. RESULTADOS La reducción de la CVRS fue mayor en pacientes en terapia triple cuando comparados con los tratados con dos drogas, siendo el momento más crítico la 12ª semana en ambos grupos. Después de la retirada del telaprevir, el grupo de terapia triple mejoró de modo significativo los puntajes de CVRS. Ansiedad y depresión en el pre tratamiento, situación de empleo y raza se mostraron relacionados con la reducción de la CVRS. CONCLUSIÓN Pacientes sometidos a la terapia doble y triple presentan reducción de los índices de CVRS, pero la adición del telaprevir les proporciona una caída más expresiva.

Resumo OBJETIVO Comparar os escores de Qualidade de Vida Relacionada à Saúde (QVRS) em pacientes com hepatite crônica C submetidos à terapia antiviral dupla e tripla e analisar os possíveis fatores relacionados à QVRS. MÉTODO A QVRS foi avaliada utilizando o Short Form 36 e oChronic Liver Disease Questionnaire , que foram aplicados antes e nas semanas 4, 12 e 16 de tratamento, em 32 pacientes divididos em 2 grupos: terapia dupla com interferon peguilado (IFN-PEG) e ribavirina e tripla com IFN-PEG, ribavirina e telaprevir. RESULTADOS A redução da QVRS foi maior em pacientes em terapia tripla quando comparados àqueles tratados com duas drogas, sendo o momento mais crítico a 12ª semana em ambos os grupos. Após a retirada do telaprevir, o grupo terapia tripla melhorou de modo significativo os escores de QVRS. Ansiedade e depressão no pré-tratamento, status empregatício e raça se mostraram relacionados à redução da QVRS. CONCLUSÃO Pacientes submetidos à terapia dupla e tripla apresentam redução dos índices de QVRS, mas a adição do telaprevir confere uma queda mais expressiva.

Female , Humans , Male , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Oligopeptides/administration & dosage , Polyethylene Glycols/administration & dosage , Quality of Life , Ribavirin/administration & dosage , Drug Therapy, Combination , Recombinant Proteins/administration & dosage
Acta ortop. mex ; 29(3): 172-175,
Article in Spanish | LILACS | ID: lil-773379


Antecedentes: La necrosis avascular de la cabeza femoral es una patología frecuente en pacientes con antecedentes de trauma, encontrándose como causas patologías vasculares, oncológicas, estados hipercoagulantes, tratamientos esteroideos prolongados, asociándose en algunos casos en pacientes con antecedente de hepatitis C con manejo con interferón pegilado + ribavirin. Seef, Foster y Poynard encontraron al estudiar el comportamiento del virus de la hepatitis, un estado de hipercoagulabilidad, que crea interrupción del flujo vascular retinacular en la cabeza femoral, sin incrementar la incidencia de osteonecrosis en este grupo de pacientes. Lauer expone que dichas infecciones virales llevan un proceso autoinmune, las cuales podrían producir vasculitis transitorias. Giampaolo en 2005 reporta la relación entre el uso de interferón en mieloma múltiple y otros padecimientos oncológicos relacionándose con necrosis avascular femoral. Material y métodos: Se valoraron los casos de diagnóstico de osteonecrosis bilateral de la cabeza femoral bilateral. Resultados: Se revisaron 5 pacientes, 4 mujeres y 1 hombre, con el diagnóstico de osteonecrosis bilateral de la cabeza femoral bilateral. Todos con antecedentes de hepatitis C con manejo con interferón pegilado, corroborándose diagnóstico definitivo por patología posterior a artroplastías, realizándose revisión bibliográfica de la relación de esta patología con el uso de interferón en pacientes con hepatitis C. Conclusiones: Al conocer la relación que existe en enfermedades virales como la hepatitis B y C con la presencia de estados de hipercoagulabilidad, procesos autoinmunes que conllevan a vasculitis transitorias y el uso de interferón pegilado 2B, relacionándose a necrosis avascular de las cabezas femorales, conoceremos nuevas causas asociadas no traumáticas a este padecimiento.

Background: Avascular necrosis of the femoral head is a frequent condition in patients with a history of trauma. The major pathologic causes include vascular diseases, malignancies, hypercoagulability states, long-term steroid treatment, and some patients have a history of hepatitis C infection treated with pegylated interferon and ribavirin. Upon studying the behavior of the hepatitis C virus, Seef, Foster and Poynard found a hypercoagulability state that causes interruption of retinacular blood flow to the femoral head, without an increased incidence of osteonecrosis in this patient group. Lauer states that such viral infections involve an autoimmune process and may result in transient vasculitides. Giampaolo, in 2005, reported the relationship between interferon use for multiple myeloma and other cancers and femoral avascular necrosis. Material and methods: Cases with a diagnosis of bilateral osteonecrosis of the femoral head were assessed. Results: Five patients were included, 4 females and one male, with a diagnosis of bilateral osteonecrosis of the femoral head. All of them had history of hepatitis C infection treated with pegylated interferon. The final diagnosis was proven by pathology after arthroplasty. A literature review was made of articles on the relationship between this condition and interferon use in patients with hepatitis C infection. Conclusions: Finding out the relationship between viral diseases such as hepatitis B and C infection and hypercoagulability states, autoimmune processes leading to transient vasculitides and the use of pegylated interferon 2B, will help us discover new nontraumatic causes associated with this condition.

Aged , Female , Humans , Male , Middle Aged , Antiviral Agents/administration & dosage , Femur Head Necrosis/etiology , Hepatitis C/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Antiviral Agents/therapeutic use , Femur Head Necrosis/pathology , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use
J. appl. oral sci ; 23(2): 215-223, Mar-Apr/2015. graf
Article in English | LILACS, BBO | ID: lil-746543


Injectable bone substitutes and techniques have been developed for use in minimally invasive procedures for bone augmentation. Objective : To develop a novel injectable thermo-sensitive alginate hydrogel (TSAH) as a scaffold to induce bone regeneration, using a minimally invasive tunnelling technique. Material and Methods : An injectable TSAH was prepared from a copolymer solution of 8.0 wt% Poly(N-isopropylacrylamide) (PNIPAAm) and 8.0 wt% AAlg-g-PNIPAAm. In vitro properties of the material, such as its microstructure and the sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2), were investigated. Then, with the subperiosteal tunnelling technique, this material, carrying rhBMP-2, was injected under the labial periosteum of the maxillary anterior alveolar ridge in a rabbit model. New bone formation was evaluated by means of X-ray, micro-computed tomography (micro-CT), fluorescence labelling, histological study, and immunohistochemistry study. Results : The material exhibited good injectability and thermo-irreversible properties. SEM showed an interconnected porous microstructure of the TSAH. The result of ALP activity indicated sustained delivery of BMP-2 from the TSAH from days 3 to 15. In a rabbit model, both TSAH and TSAH/rhBMP-2 induced alveolar ridge augmentation. The percentage of mineralised tissue in the TSAH/rhBMP-2 group (41.6±3.79%) was significantly higher than in the TSAH group (31.3±7.21%; p<0.05). The density of the regenerating tissue was higher in the TSAH/rhBMP-2 group than in the other groups (TSAH group, positive control, blank control; p<0.05). Conclusions : The TSAH provided convenient handling properties for clinical application. To some extent, TSAH could induce ridge augmentation and mineral deposition, which can be enhanced when combined with rhBMP-2 for a minimally invasive tunnelling injection. .

Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Brain Injuries/drug therapy , Brain/drug effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Receptors, Interleukin-1/antagonists & inhibitors , Brain Injuries/immunology , Brain Injuries/pathology , Brain/immunology , Brain/pathology , Cytokines/analysis , Cytokines/immunology , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin 1 Receptor Antagonist Protein/adverse effects , Receptors, Interleukin-1/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use
Braz. j. infect. dis ; 19(1): 15-22, Jan-Feb/2015. tab
Article in English | LILACS | ID: lil-741237


Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...

Adult , Female , Humans , Male , Middle Aged , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Antiviral Agents/adverse effects , Cohort Studies , Drug Therapy, Combination , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Interferon-alpha/adverse effects , Polyethylene Glycols/adverse effects , Retrospective Studies , RNA, Viral , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Ribavirin/adverse effects , Treatment Outcome , Viral Load
Clinics ; 69(8): 547-553, 8/2014. tab, graf
Article in English | LILACS | ID: lil-718187


OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...

Adult , Aged , Female , Humans , Male , Middle Aged , Anemia/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Erythropoietin/therapeutic use , Anemia/complications , Brazil , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Double-Blind Method , Erythropoietin/administration & dosage , Erythropoietin/adverse effects , Follow-Up Studies , Hemoglobins/analysis , Iron/blood , Iron/therapeutic use , Renal Dialysis , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Renal Insufficiency, Chronic/complications , Treatment Outcome
Braz. j. infect. dis ; 18(1): 48-52, Jan-Feb/2014. tab
Article in English | LILACS | ID: lil-703055


Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Female , Humans , Male , Middle Aged , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Liver Cirrhosis/etiology , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Antiviral Agents/adverse effects , Drug Therapy, Combination/methods , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Interferon-alpha/adverse effects , Predictive Value of Tests , Polyethylene Glycols/adverse effects , Retrospective Studies , RNA, Viral/genetics , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Ribavirin/adverse effects , Severity of Illness Index , Viral Load
Gut and Liver ; : 421-427, 2014.
Article in English | WPRIM | ID: wpr-175278


BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon alpha-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, alpha-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Adult , Aged , Female , Humans , Male , Young Adult , Administration, Oral , Antiviral Agents/administration & dosage , Area Under Curve , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/drug therapy , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Medication Adherence , Polyethylene Glycols/administration & dosage , Prospective Studies , RNA, Viral/metabolism , Recombinant Proteins/administration & dosage , Ribavirin/administration & dosage , Treatment Outcome , Viral Load
Yonsei Medical Journal ; : 1042-1048, 2014.
Article in English | WPRIM | ID: wpr-113970


PURPOSE: The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage(TM)) supplement in patients with growth hormone deficiency were evaluated. MATERIALS AND METHODS: This trial is 12-week prospective, single-arm, open-label trial. Men and women aged > or =20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. RESULTS: The IGF-1 level of 108.67+/-74.03 ng/mL was increased to 129.01+/-68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80+/-6.51 to 7.55+/-5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. CONCLUSION: Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.

Adult , Aged , Female , Humans , Male , Middle Aged , Delayed-Action Preparations , Growth Hormone/administration & dosage , Human Growth Hormone/deficiency , Prospective Studies , Recombinant Proteins/administration & dosage
Cad. saúde pública ; 29(supl.1): s146-s158, Nov. 2013. ilus, graf, tab
Article in Portuguese | LILACS | ID: lil-690747


Evidências recentes demonstram que respondedores virológicos lentos podem se beneficiar com a extensão do tratamento antiviral. O estudo investigou a adoção desse protocolo diante da coinfecção VHC/HIV. O objetivo foi estudar a relação de custo/efetividade da terapêutica com peguinterferon associado à ribavirina em portadores do genótipo 1 do VHC coinfectados com o HIV, comparando-se a inclusão ou não de respondedores virológicos lentos. Simulou-se por meio de um modelo de Markov a progressão da doença hepática em uma coorte hipotética de mil homens, maiores de 40 anos, considerandose a perspectiva do Sistema Único de Saúde (SUS) e horizonte temporal de 30 anos. A extensão do tratamento para respondedores lentos resultou em uma razão incremental de custo efetividade de R$ 44.171/QALY, valor abaixo do limiar de aceitabilidade proposto pela Organização Mundial da Saúde. A análise de sensibilidade não modificou os resultados alcançados. A inclusão de indivíduos coinfectados VHC/HIV respondedores virológicos lentos no protocolo de tratamento apresenta-se como uma estratégia custo-efetiva para o SUS.

Recent evidence has demonstrated that slow responders may benefit from antiviral treatment in HCV/HIV coinfection. This study aimed to evaluate the cost-effectiveness of HCV treatment in individuals with genotype 1 coinfected with HIV, with peg-interferon in combination with ribavirin, compared to the inclusion (versus non-inclusion) of slow responders. A Markov model was developed that simulated the progression of liver disease in a hypothetical cohort of one thousand men over 40 years of age, considering the Brazilian Unified National Health System (SUS) perspective and a 30-year timeline. The extension of treatment to slow responders provided a 60% increase in the number of individuals who eliminated HCV and an incremental cost-effectiveness ratio of 44,171 BRL/QALY, below the acceptability threshold proposed by World Health Organization. Sensitivity analysis did not alter the results. The inclusion of HCV/ HIV-coinfected slow virologic responders in the treatment protocol is shown to be a cost-effective strategy for the SUS.

La evidencia reciente ha demostrado que los individuos con respuesta virológica lenta pueden beneficiarse de una extensión del tratamiento antiviral. El estudio investigó la adopción de este protocolo antes de la coinfección por VHC/HIV. El objetivo fue estudiar la relación coste-efectividad de la terapia con peginterferon asociado con ribavirina en pacientes con genotipo 1 del VHC, coinfectados por el HIV respondedores virológicos lentos. Se simula mediante un modelo de Markov la progresión de la enfermedad hepática en una cohorte hipotética de un millar de hombres, más de 40, teniendo en cuenta la perspectiva del Sistema Único de Salud (SUS) y un horizonte temporal de 30 años. El grado de tratamiento a los respondedores lentos dio lugar a un incremento de coste-efectividad de R$ 44.171/QALY, por debajo del umbral de aceptabilidad propuesto por la Organización Mundial de la Salud. El análisis de sensibilidad no modificó los resultados. La inclusión de los individuos coinfectados y con respuesta virológica lenta en el protocolo de tratamiento se presenta como una estrategia económica para el SUS.

Adult , Humans , Male , Antiviral Agents/administration & dosage , HIV Infections , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Antiviral Agents/economics , Coinfection , Cost-Benefit Analysis , Drug Therapy, Combination/economics , Interferon-alpha/economics , Polyethylene Glycols/economics , Recombinant Proteins/administration & dosage , Recombinant Proteins/economics , Ribavirin/economics
Braz. j. infect. dis ; 17(5): 555-563, Sept.-Oct. 2013. ilus, tab
Article in English | LILACS | ID: lil-689881


BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCVRNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

Humans , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Hepatitis C/genetics , Insulin Resistance/physiology , RNA, Viral/genetics , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/physiopathology , Hepatitis C/classification , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Recombinant Proteins/administration & dosage , Ribavirin/administration & dosage , Viral Load