ABSTRACT
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Apoptosis , China , Disease-Free Survival , East Asian People , Immunotherapy , Interferon-alpha/therapeutic use , Lymphatic Metastasis , Melanoma/pathology , Programmed Cell Death 1 Receptor/therapeutic use , Skin Neoplasms/pathology , Melanoma, Cutaneous MalignantABSTRACT
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Apoptosis , China , Disease-Free Survival , East Asian People , Immunotherapy , Interferon-alpha/therapeutic use , Lymphatic Metastasis , Melanoma/pathology , Programmed Cell Death 1 Receptor/therapeutic use , Skin Neoplasms/pathology , Melanoma, Cutaneous MalignantABSTRACT
Objective@#This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB).@*Methods@#HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks.@*Results@#A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05).@*Conclusion@#There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.
Subject(s)
Humans , Biomarkers , Cytokines , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic useABSTRACT
Objective@#To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months.@*Results@#In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( @*Conclusion@#During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.
Subject(s)
Adult , Female , Humans , Male , Antiviral Agents/therapeutic use , Cytokines/blood , Guanine/therapeutic use , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Prospective Studies , Recombinant Proteins/therapeutic useABSTRACT
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Ribavirin/therapeutic use , Technology Assessment, Biomedical , Ursodeoxycholic Acid/therapeutic use , Immunoglobulins/therapeutic use , Prednisolone/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Chloroquine/therapeutic use , Cross-Sectional Studies , Cohort Studies , Interferon-alpha/therapeutic use , Tacrolimus/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Ritonavir/therapeutic use , Antibodies, Neutralizing/therapeutic use , Mesenchymal Stem Cells , Lopinavir/therapeutic use , Folic Acid/therapeutic use , Meropenem/therapeutic use , Hydroxychloroquine/therapeutic use , Antibodies, Monoclonal/therapeutic use , Mycophenolic Acid/therapeutic useABSTRACT
INTRODUCCIÓN: En diciembre del 2019 se identificó en Wuhan (China) una serie de pacientes con infecciones respiratorias que en algunos casos evolucionaban en una neumonía viral grave, entre el 1 al 5% de los casos requerían de cuidados intensivos. El 7 de enero del 2020, las autoridades chinas anunciaron a un "nuevo coronavirus" como el agente causante de estas infecciones. La OMS denomino a este virus Covid-19. Esta enfermedad se ha diseminado a todo el mundo, causando una gran repercusión social y económica. Actualmente no existe un tratamiento específico para la enfermedad, brindándose tratamiento de soporte para todos los casos. Se han administrado algunos fármacos específicos para tratar la enfermedad, pero no hay recomendaciones concluyentes. OBJETIVO: Revisar la literatura científica sobre las intervenciones farmacológicas para el tratamiento de la enfermedad por el coronavirus 2019 (COVID 19). METODOLOGÍA: Se desarrolló una búsqueda electrónica en la base de datos Medline (a través de Pubmed). Para tal fin, se construyó una estrategia de búsqueda sistemática, utilizando términos del lenguaje natural y descriptores de lenguaje controlado, teniendo como fecha de búsqueda desde el 01 de diciembre de 2019 (mes donde se reportó los primeros casos de COVID-19 en China) hasta el 20 de marzo de 2020. Se incluyó únicamente estudios publicados en idioma español o inglés. RESULTADOS: Se identificaron 947 referencias potencialmente relevantes. Tras la remoción de duplicados, y lectura de títulos y resúmenes, se seleccionaron 43 referencias para lectura a texto completo. Finalmente, se seleccionaron 15 estudios que respondieron a la pregunta PICO de interés. CONCLUSIONES: No existe a la fecha, ninguna intervención farmacológica que haya demostrado ser efectivo y segura para tratamiento de COVID-19. La calidad de la evidencia para los desenlaces reportados por los ensayos clínicos donde se evaluó Favipiravir y Lopinavir/ritonavir fue calificada como baja (Es muy probable que nuevos estudios tengan un impacto importante en la confianza que se tiene en el resultado estimado y que estos puedan modificar el resultado. La calidad de la evidencia para los desenlaces reportados por el ensayos clínico donde se evaluó Hidroxicloroquina es Muy Baja (Cualquier resultado estimado es muy incierto). No se identificó evidencia concluyente respecto al uso de Lopinavir más interferón α2b, el único estudio encontrado correspondió a una serie de 10 pacientes. Asímismo, la evidencia encontrada respecto a la combinación de arbidol y lopinavir/ritonavir se basa en serie de casos, que son estudios con muchas limitaciones, por lo que sus resultados deben analizarse con cuidado. No se obtuvo evidencia concluyente sobre el uso de arbidol, esta se basa únicamente en series de casos, con un pequeño número de pacientes. No se obtuvo evidencia concluyente sobre el uso de interferón alfa, sólo se encontró un reporte de caso.(AU)
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Interferons/therapeutic use , Interferon-alpha/therapeutic use , Coronavirus Infections/drug therapy , Ritonavir/therapeutic use , Lopinavir/therapeutic use , Hydroxychloroquine/therapeutic use , Technology Assessment, Biomedical , Health EvaluationABSTRACT
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 11 protocolos.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Technology Assessment, Biomedical , Immunoglobulins/therapeutic use , Vaccines/therapeutic use , Chloroquine/therapeutic use , Colchicine/therapeutic use , Cross-Sectional Studies/instrumentation , Cohort Studies , Interferon-alpha/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Ritonavir/therapeutic use , Lopinavir/therapeutic use , Fibrinolytic Agents/therapeutic use , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/therapeutic useABSTRACT
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos e 26 protocolos.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Technology Assessment, Biomedical , Immunoglobulins/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heparin/therapeutic use , Interferon-alpha/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Mesenchymal Stem Cells , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/therapeutic useABSTRACT
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Acetylcysteine/therapeutic use , Technology Assessment, Biomedical , gamma-Globulins/therapeutic use , Immunoglobulins/therapeutic use , Methylprednisolone/therapeutic use , BCG Vaccine , Influenza Vaccines , Famotidine/therapeutic use , Autohemotherapy , Chloroquine/therapeutic use , Colchicine/therapeutic use , Interferon-alpha/therapeutic use , Ritonavir/therapeutic use , Pneumococcal Vaccines , Lopinavir/therapeutic use , Observational Study , Nitric Oxide/therapeutic useABSTRACT
La infección crónica por el virus de la hepatitis B (VHB) se considera un problema de salud pública mundial. Se estima que al menos dos mil millones de personas han estado expuestas al VHB, y a pesar de una vacuna efectiva, 300 millones de personas están infectadas crónicamente a nivel mundial. Aunque el virus no es directamente citopático, la infección puede desencadenar cirrosis hepática y aun, carcinoma hepatocelular (CHC). El ADN circular cerrado covalentemente (ADNccc) en el núcleo de los hepatocitos y la incapacidad del sistema inmunitario para eliminar la infección crónica por el virus son los mecanismos más importantes de la infección por VHB. Las diferentes entidades, como la Asociación Europea para el Estudio del Hígado (EASL) y la Asociación Americana para el Estudio de las Enfermedades Hepáticas (AASLD), ponen a disposición las pautas para el manejo de esta enfermedad. A pesar de los avances en el tratamiento de la infección crónica por el VHB, en particular con el desarrollo de los análogos de los nucleótidos/ nucleósidos, quedan aún muchos interrogantes. Las investigaciones continúan para el desarrollo de nuevas opciones de tratamiento enfocadas principalmente en evitar que la suspensión de la terapia conlleve a un incremento de la carga viral, con el consecuente aumento del riesgo de progresión de la enfermedad hepática, y un eventual CHC.
Chronic hepatitis B virus (HBV) infection is considered a global public health problem. It is estimated that at least two billion people have been exposed to HBV, and despite an effective vaccine, 300 million people are chronically infected worldwide. Although the virus is not directly cytopathic, the infection can trigger liver cirrhosis and even hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes and the inability of the immune system to eliminate chronic virus infection are the most important mechanisms of chronic HBV infection. Different entities, such as the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), provide guidelines for the management of this disease. Despite advances in the treatment of chronic HBV infection, including the development of nucleotide and nucleoside analogs, many questions remain. Research continues for the development of new treatment options focused mainly on avoiding a relapse on viral load after therapy discontinuation, with an increased risk of liver disease progression, and an eventual CHC.
Subject(s)
Humans , Hepatitis B, Chronic/drug therapy , Polyethylene Glycols/therapeutic use , Interferon-alpha/therapeutic use , Viral Load , Hepatitis B, Chronic/immunology , Nucleosides/analogs & derivatives , NucleotidesABSTRACT
ABSTRACT The Brazilian Public Health Service provides freely αPEG-IFN to treat patients infected with HCV. The primary goal of HCV therapy is the long-term elimination of HCV from the blood to reduce the risk of HCV associated complications and death. Patient viremia affects the treatment duration and response, thus influencing clinical decisions. We developed a high-throughput method to perform the quantification of RNA hepatitis C virus (HCV) virus load in plasma samples to monitor patients under treatment. The method is based on a duplex detection, in a one-step real-time RT-PCR assay and it has been validated according to the rules established by the official Brazilian regulatory agency (ANVISA). This new method was compared to a commercial kit (Cobas/Taqman HCV Test v2.0 - Roche), showing virus load results with significant correlation between them (p= 0,012) using commercial and clinical panels. In addition, 611 samples from patients treated with peguilated alfa-interferon (αPEG-IFN) from different regions of Brazil were analyzed. Our one-step real-time RT-PCR assay demonstrated good performance in viral load measurement and in treatment course monitoring, with acceptable sensitivity and specificity values.
Subject(s)
Humans , RNA, Viral/isolation & purification , Hepatitis C/virology , Hepacivirus/isolation & purification , Viral Load/methods , Real-Time Polymerase Chain Reaction/methods , Antiviral Agents/therapeutic use , Polyethylene Glycols/therapeutic use , Time Factors , Viremia , Recombinant Proteins/therapeutic use , Brazil , RNA, Viral/genetics , RNA, Viral/blood , Prospective Studies , Reproducibility of Results , Interferon-alpha/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/blood , Hepacivirus/genetics , Genotyping Techniques , GenotypeABSTRACT
ABSTRACT CONTEXT: Recurrent respiratory papillomatosis (RRP) is the most common laryngeal tumor. During childhood, it may present in extremely severe forms defined by the need for frequent surgical procedures to relieve respiratory distress and/or involvement of extralaryngeal sites such as lung involvement. Adjuvant therapies are indicated in these cases and interferon is one of the options. Pegylated interferon is more effective than conventional alpha interferon and, given its reported results in relation to treating hepatitis C over the past decade, we hypothesized that this might be more effective than conventional interferon also for treating respiratory papillomatosis. Use of a treatment strategy that eliminates the need for general anesthesia is particularly appealing, yet obtaining approval for use of medications that are not currently used for this purpose is challenging. CASE REPORT: We report the case of a child with severe RRP that had been followed for the preceding six years, who was treated with pegylated interferon after failure of other adjuvant therapies. There was noticeable improvement in the frequency of surgical procedures, which was regarded very receptively, considering the child's history and previous response to other therapies. CONCLUSION: Pegylated interferon may be a good option for diminishing the need for surgical intervention in severe cases of recurrent respiratory papillomatosis.
Subject(s)
Humans , Male , Infant , Antiviral Agents/therapeutic use , Polyethylene Glycols/therapeutic use , Respiratory Tract Infections/drug therapy , Interferon-alpha/therapeutic use , Papillomavirus Infections/drug therapy , Interferon alpha-2/therapeutic use , Severity of Illness Index , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
ABSTRACT BACKGROUND: The interaction between serum lipids and C virus infection is well known, as are serum lipid levels in the Peg-IFN / RBV-based treatment. However, with direct action antivirals (DAAs) this behavior is still unclear. OBJECTIVE: To compare serum lipids levels between patients treated with Peg-IFN/RBV and DAAs and to evaluate lipids in sustained virological response (SVR) with DAAs. METHODS: Retro prospective study comparing the behavior of total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides (TG) serum levels during treatment with DAAs (G-DAAs) and a control historic group Peg-IFN/RBV (G-PR). Coorte, prospective study, to study the behavior of lipids in the SVR with DAAs. Data were collected at the beginning of treatment (baseline: t-base) and at week 12 of treatment (t-12) for G-DAAs and at week 24 (t-24) for G-PR, groups. In the cohort evaluation, the samples at t-base and at week 12 after the end of treatment (t-SVR). Delta lipids: difference between lipids in t-12 / t-24 minus t-base for comparison between G-PR and G-AADs groups and t-SVR minus t-base for lipid analysis in SVR. Analysis with Kruskal Wallis and Wilcoxon tests to compare the delta lipids of the groups. The P value was 0.05. RESULTS: In the assessment between G-PR and G-DAAs groups, we included 63 and 121 patients, respectively. The groups did not differ one from the other (BMI, sex, genotype, fibrosis, total cholesterol, LDL, and TG) except by age (50.38±10.44 vs 56±9.69, P=0.0006). We observed a decrease in levels of TC and LDL and an increase in TG, in G-PR, and in G-DAAs the opposite (Δ TC -13.9±34.5 vs 4.12±34.3 P=0.0005, Δ LDL -7.16±32 vs 10.13±29.92, P=0.003, Δ TG 4.51±53.7 vs -8.24±49.93, P=0.0025). In the coorte analysis, we included 102 patients, 70% men and 56% F4, 95 of them reached SVR. We observed an increase of TC and LDL and a decrease of TG in both groups (SVR and non SVR), with no statistical difference (Δ TC P=0.68; Δ LDL P=0.69; Δ TG P=0.43). We did not find significant difference in delta evaluation by genotype 1 and 3 (Δ TC +29.7±40.2 vs +13.4±30.3, P=0.06; Δ LDL +21.4±28.6 vs +16.6±31.3, P=0.41; Δ TG -3.6±60.6 vs -0.7±40, P=0.91). CONCLUSION: Serum lipids level differed during treatment with Peg-IFN and DAAs. Treatment with DAAs was associated with an increase of TC and LDL and a decrease of TG, independently of SVR.
RESUMO CONTEXTO: A interação entre lípides séricos e infecção pelo vírus C já é bem conhecida, assim como o comportamento dos níveis séricos daqueles durante o tratamento com Peg-IFN/RBV. No entanto, com antivirais de ação direta (AADs) este comportamento ainda não está claro. OBJETIVO: Comparar os níveis séricos de lípides entre pacientes tratados com Peg-IFN/RBV e AADs e avaliar os lípides na resposta virológica sustentada (RVS) com AADs. MÉTODOS: Estudo retro prospectivo comparando o comportamento dos níveis séricos de colesterol total (CT), lipoproteínas de baixa densidade (LDL) e triglicérides (TG) durante o tratamento com AADs (G-AADs) e um grupo histórico de controle Peg-IFN/RBV (G-PR). Coorte, estudo prospectivo, para estudar o comportamento dos lípides na RVS com AADs. Os dados foram coletados no início do tratamento (baseline: t-base) e na décima segunda semana de tratamento (t-12) para G-AADs e na vigésima quarta semana de tratamento (t-24) para G-PR para a análise comparativa entre os dois grupos. Na avaliação de coorte, as amostras foram coletadas no t-base e na décima segunda semana após o término do tratamento (t-RVS). Delta lípides: diferença entre lípides em t-12/t-24 menos t-base para comparação entre os grupos G-PR e G-AADs e t-RVS menos t-base para análise de lípides na RVS. A análise estatística descritiva, os testes não paramétricos de Kruskal Wallis e Wilcoxon foram utilizados para comparar o delta lípides dos grupos. O valor de P considerado foi de 0,05. RESULTADOS: Na avaliação entre os grupos G-PR e G-AADs, incluímos 63 e 121 pacientes, respectivamente. Os grupos não diferiram um do outro (IMC, sexo, genótipo, fibrose, colesterol total, LDL e TG), exceto por idade (50,38±10,44 vs 56±9,69, P=0,0006). Observamos uma diminuição nos níveis de CT e LDL e um aumento de TG no G-PR, no G-AADs ocorreu o oposto (Δ CT -13,9±34,5 vs 4,12±34,3 P=0,0005, Δ LDL -7,16±32 vs 10,13±29,92, P=0,003, Δ TG 4,51±53,7 vs -8,24±49,93, P=0,0025). Na análise de coorte, foram incluídos 102 pacientes, 70% homens e 56% F4. Noventa e cinco deles atingiram a RVS. Observamos um aumento de CT e LDL e uma diminuição de TG em ambos os grupos (RVS e não RVS), sem diferença estatística (Δ CT P=0,68; Δ LDL P=0,69; Δ TG P=0,43). Não encontramos diferença significativa na avaliação dos deltas pelos genótipos 1 e 3 (Δ CT +29,7±40,2 vs +13,4±30,3, P=0,06; Δ LDL + 21,4±28,6 vs +16,6±31,3, P=0,41; Δ TG -3,6±60,6 vs -0,7±40, P=0,91). CONCLUSÃO: O nível de lípides séricos diferiu durante o tratamento com Peg-IFN/RBV e AADs. O tratamento com AADs foi associado a um aumento de CT e LDL e uma diminuição de TG, independentemente da RVS.
Subject(s)
Humans , Male , Female , Adult , Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Hepacivirus/genetics , Sustained Virologic Response , Lipids/blood , Antiviral Agents/pharmacology , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Triglycerides/blood , Recombinant Proteins/therapeutic use , Prospective Studies , Interferon-alpha/therapeutic use , Hepatitis C/virology , Hepacivirus/drug effects , Drug Therapy, Combination , Genotype , Cholesterol, LDL/blood , Middle AgedABSTRACT
ABSTRACT BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.
RESUMO CONTEXTO: A resistência insulínica e o diabetes mellitus são frequentes manifestações extra-hepáticas da hepatite C crônica. A resistência insulínica medida pelo HOMA-IR está associada a uma baixa taxa de resposta virológica sustentada, principalmente em pacientes portadores de hepatite C crônica genótipo 1 tratados com peginterferon/ribavirina. Em relação aos pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina, a influência da resistência insulínica na resposta virológica sustentada ainda não está esclarecida. OBJETIVO: Avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3. MÉTODOS: Estudo multicêntrico retrospectivo foi realizado para avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes não-diabéticos portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina. Um total de 200 pacientes portadores de hepatite C crônica genótipo 3 foi incluído no estudo. Todos os pacientes eram não diabéticos e apresentavam medida de HOMA-IR antes do início do tratamento da hepatite C crônica com peginterferon/ribavirina. A duração do tratamento foi de pelo menos 24 semanas. O cut-off de HOMA-IR foi definido para este estudo como ≥2,5 devido ao coeficiente de correlação com a resposta virológica sustentada de 0,202 (P=0,004). RESULTADOS: Na análise univariada, idade, aspartato aminotransferase, plaquetas, grau de fibrose e HOMA-IR foram preditores de resposta virológica sustentada. No entanto, na análise multivariada, apenas fibrose avançada [OR=2,01 (95%IC: 0,986-4,119) P=0,05] e idade [OR=1,06 (95%IC: 1,022-1,110) P=0,002] estavam relacionados como preditores negativo de resposta virológica sustentada. CONCLUSÃO: Neste estudo multicêntrico, retrospectivo, em pacientes não diabéticos portadores de hepatite C genótipo 3, a resistência insulínica não estava associada à resposta virológica sustentada em pacientes tratados com peginterferon/ribavirina.
Subject(s)
Humans , Male , Female , Antiviral Agents/therapeutic use , Ribavirin/therapeutic use , Insulin Resistance/physiology , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Retrospective Studies , Interferon-alpha/therapeutic use , Viral Load , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Genotype , Homeostasis/physiologyABSTRACT
RESUMEN El virus de la hepatitis C es la principal infección trasmitida por los derivados de la sangre en los Estados Unidos, con 3.2 millones de individuos infectados. El alfa interferón inyectable ha sido históricamente la piedra angular en la terapia del virus de hepatitis C. Se revisaron las publicaciones los trabajos publicados en Medline, Scielo, PubMed, e Hinari, hasta comienzos del año 2016. Las principales palabras clave utilizadas fueron virus de la hepatitis C, hepatitis C crónica, Interferón, antivirales. Recientes adelantos han llevado a la disponibilidad de nuevos medicamentos antivirales, que con el desarrollo de nuevas terapias orales libres de interferón han convertido la terapia del virus de la hepatitis C más eficaz además de simplificar los regímenes del tratamiento. Aunque estos regímenes de tratamiento aún permanecen complicados, las nuevas recomendaciones y guías evolucionan rápidamente. El rápido desarrollo de nuevas terapias para la hepatitis C, han logrado métodos más eficaces con menos reacciones adversas que optimizan el tratamiento de estos enfermos (AU).
ABSTRACT The hepatitis C virus is the main infection transmitted by blood products in the United States, with 3.2 million of infected individuals. The injected alpha interferon has historically been the key stone in the therapy of the hepatitis C virus. The works published in Medline, Scielo, PubMed and Hinary until the beginning of 2016 were reviewed. The main used key words were HVC, cronic hepatitis C, interferon, antivirals. Recent advances have led to the availability on new antiviral drugs, developing new interferon-free oral therapies that make the therapy of hepatitis C virus more efficacious and make easier the treatment regimens. Although these treatment regimens are still complicated, the new recommendations and guidelines evolve quickly. The fast development of new therapies against hepatitis C has led to more efficacious methods with less adverse reactions, optimizing the treatment of these patients (AU).
Subject(s)
Humans , Antiviral Agents , Virology/methods , Risk Factors , Interferon-alpha/therapeutic use , Hepacivirus/pathogenicity , Hepatitis C, Chronic/epidemiology , Epidemiological Monitoring , United States/epidemiology , Hepacivirus/drug effects , Clinical Laboratory Techniques/methods , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/prevention & control , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/transmission , Cuba/epidemiology , Kidney Function Tests/methods , Liver Function TestsABSTRACT
ABSTRACT BACKGROUND: Recent studies have questioned the recommendation of abstinence from alcohol for at least 6 months for alcoholic patients to be treated for hepatitis C. OBJECTIVE: The present study aimed to assess the impact of alcohol consumption among patients undergoing hepatitis C treatment. METHODS: In this cross-sectional study, 121 patients [78 (64.5%) men; 28-70 years] were evaluated. They were divided as follows: patients who consumed <12 g of ethanol/day throughout life (Group 1), 12-59 g/day (Group 2) and ≥60 g/day (Group 3). Patients were treated with pegylated-interferon plus ribavirin. RESULTS: These three groups could not be distinguished in terms of the severity of liver fibrosis and frequency of HCV genotype-1 infection. In Group 3, treatment discontinuation (32.4%) was higher than in the Group 1 (9.4%) or Group 2 (0%), it was higher among patients who drank during treatment (66.7% vs 21.4%) and among those who had not been abstinent for at least 6 months (72.7% vs 15.4%). Moderate alcohol drinkers showed good adherence and did not discontinue the treatment. The frequencies of sustained viral response among patients in Group 3 (44.4%) were similar to those in Group 1 (61%) and Group 2 (68.4%). CONCLUSION: Heavy drinkers more often discontinued treatment for hepatitis C, but those that received this treatment had acceptable sustained viral response rates. These results suggest that heavy drinkers should not be systematically excluded from the treatment, but they should be monitored to avoid drinking and abandoning treatment, mainly those who have not been abstinent for at least 6 months.
RESUMO CONTEXTO: Estudos recentes têm questionado a recomendação de abstinência do álcool por pelo menos 6 meses para pacientes alcoolistas serem tratados para hepatite C. OBJETIVO: Este estudo objetivou avaliar o impacto do consumo de álcool entre pacientes submetidos ao tratamento para a hepatite C. MÉTODOS: Neste estudo transversal, avaliou-se 121 pacientes [78 (64,5%) homens; 28-70 anos). Eles foram divididos em três grupos: pacientes que consumiam <12 g de etanol/dia na vida (Grupo 1); 12-59 g/dia (Grupo 2) e ≥60 g/dia (Grupo 3). Pacientes foram tratados com interferon-peguilado mais ribavirina. RESULTADOS: Os três grupos não puderam ser distinguidos em relação à gravidade da fibrose hepática e das frequências de infecção pelo genótipo-1 do HCV. No Grupo 3, descontinuação do tratamento (32,4%) foi maior do que no Grupo 1 (9,4%) ou Grupo 2 (0%), foi maior entre pacientes que beberam durante o tratamento (66,7% vs 21,4%) e entre aqueles que não estavam em abstinência por pelo menos 6 meses (72,7% vs 15,4%). Pacientes do Grupo 2 tiveram boa aderência e não descontinuaram o tratamento. As frequências de resposta virológica sustentada entre pacientes do Grupo-3 (44,4%) foi semelhante àquelas do Grupo 1 (61%) e do Grupo 2 (68,4%). CONCLUSÃO: Bebedores pesados mais frequentemente descontinuaram o tratamento da hepatite C, mas aqueles que foram tratados tiveram aceitáveis taxas de resposta virológica sustentada. Esses resultados sugerem que bebedores pesados não deveriam ser sistematicamente excluídos do tratamento, mas sim serem monitorados para evitar beber e abandonar o tratamento, principalmente aqueles que não estão abstinentes por pelo menos 6 meses.
Subject(s)
Humans , Male , Female , Adult , Aged , Antiviral Agents/therapeutic use , Ribavirin/therapeutic use , Interferon-alpha/therapeutic use , Hepatitis C/complications , Hepatitis C/drug therapy , Alcoholism/complications , Socioeconomic Factors , Recombinant Proteins/therapeutic use , Cross-Sectional Studies , Withholding Treatment , Interferon alpha-2 , Middle AgedABSTRACT
ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.
RESUMO CONTEXTO A infecção gástrica pelo Helicobacter pylori (H. pylori) é principal causa de alterações inflamatórias e de câncer gástrico. OBJETIVO O objetivo deste estudo foi encontrar os efeitos da cúrcuma no estresse oxidativo e as alterações histológicas na gastrite crônica associada ao H. pylori. MÉTODOS Em um estudo randomizado clínico experimental, pacientes foram divididos em dois grupos: um grupo de terapia tríplice padrão e outro com terapia tríplice com e cúrcuma. Exames endoscópicos e histológicos foram analisados para todos os pacientes antes e depois de 8 semanas de tratamento. RESULTADOS A terapia tríplice com grupo de tratamento de cúrcuma diminuiu significativamente os marcadores de malondialdeído, de peróxidos de glutationa, com aumento da capacidade antioxidante total da mucosa gástrica ao final do estudo em comparação com grupos de regime basal e tríplice. Além disso, o dano oxidativo ao DNA diminuiu significativamente em terapia tríplice com grupo de cúrcuma no final do estudo em comparação com a linha de base e comparado à terapia tríplice (P<0,05 para ambos). No grupo de terapia tríplice em combinação com cúrcuma houve diminuição significativa de todas os escores ativos de inflamação crônica e endoscópica dos pacientes em relação ao grupo de terapia de base e tríplice (P<0,05 para ambos). A taxa de erradicação por terapia tríplice + cúrcuma aumentou significativamente em relação à terapia tríplice isolada (P<0,05). CONCLUSÃO A cúrcuma pode ser um complemento útil para melhorar a inflamação crônica e prevenção de alterações cancerígenas em pacientes com gastrite crônica associada ao H.pylori.
Subject(s)
Humans , Male , Female , Adult , Aged , Antiviral Agents/therapeutic use , Ribavirin/therapeutic use , Interferon-alpha/therapeutic use , Hepatitis C/complications , Hepatitis C/drug therapy , Alcoholism/complications , Socioeconomic Factors , Recombinant Proteins/therapeutic use , Cross-Sectional Studies , Withholding Treatment , Interferon alpha-2 , Middle AgedABSTRACT
ABSTRACT Background Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. Objective The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients. Methods A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Results Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). Conclusion - In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals.
RESUMO Contexto Em virtude da elevada prevalência da coinfecção pelos vírus da hepatite C (HCV) e da imunodeficiência humana (HIV) e às inúmeras complicações que esses vírus acarretam, é fundamental o maior entendimento do comportamento biológico dos mesmos. O polimorfismo de nucleotídeo único rs1045642 C3435T do gene de resistência a múltiplas drogas MDR1, no qual ocorre modificação do códon ATC para ATT, parece estar relacionado à resposta virológica sustentada ao tratamento do HCV em coinfectados HCV-HIV. Objetivo Mapear o polimorfismo C3435T do gene MDR1 em pacientes coinfectados HCV-HIV e correlacionar com dados clínicos e laboratoriais. Métodos Foram analisados 99 pacientes coinfectados HCV-HIV. A identificação molecular do polimorfismo de nucleotídeo único rs1045642 do gene MDR1 foi realizada pela técnica de PCR em tempo real (qPCR) alelo-específico com primers e sondas específicos para a identificação desse polimorfismo. Fatores de risco para a aquisição do HCV e a resposta virológica sustentada ao tratamento do HCV com interferon-alfa peguilado e ribavirina foram analisados. Resultados Dentre os pacientes avaliados, 54 (54,5%) eram do gênero masculino e 45 (45,5%) do gênero feminino. A média de idade foi de 46,1 anos (±9,8). As frequências dos genótipos CC, CT e TT foram 28,3%, 47,5% e 24,2% respectivamente, e as frequências alélicas foram 52% para alelo C e 48% para alelo T. Não houve associação entre o gene MDR1 e a resposta virológica sustentada (P=0,308). Conclusão Neste estudo, o polimorfismo C3435T no gene MDR1 não apresentou associação com a resposta virológica sustentada ao tratamento em indivíduos coinfectados HCV-HIV.