BioHabana 2022: Preventive and Immunotherapeutic Strategies Against COVID-19 and Cancer in Cuba.

The convergence of life sciences with neurosciences, nanotechnology, data management, and engineering has caused a technological diversification of the biotechnology, pharmaceutical, and medical technology industries, including the phenomenon of digital transformation, which has given rise to the so-called Fourth Industrial Revolution (Industry 4.0). Confronting the COVID-19 pandemic revealed the outstanding response capacity of the scientific community and the biopharmaceutical industry, based on a multidisciplinary and interinstitutional approach that has achieved an unprecedented integration in the history of biomedical science. Cuba, a small country, with scarce material resources, has had remarkable success in controlling the disease, which also highlights the impact of social factors. This report presents a summary of the most relevant presentations of selected topics during the scientific meeting, "BioHabana 2022: Cancer Immunotherapy and the COVID-19 Pandemic," which was held in Havana Cuba in April 2022.

Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial.

ObjectivesAn IFN-2b and IFN-{gamma} combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of a host from a SARS-CoV-2 infection. Considering this synergy, we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN - 2b and IFN-{gamma} administration in patients positive for SARS-CoV-2. MethodsWe enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-2b and 0.5 MIU IFN-{gamma} (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-2b (Heberon(R) Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir (200/50 mg every 12 h) and chloroquine (250 mg every 12 h, i.e.standard of care). The primary endpoints were, from the start of treatment, the time to elimination of viral RNA and the time to progression to severe COVID-19. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant (INSTITUTION PROTOCOL IG/IAG/CV/2001). ResultsA total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral elimination, of these 78.6% in the HeberFERON group eliminated the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the elimination of SARS-CoV-2, as measured by RT-PCR was 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for virus elimination was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to the Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-2b groups, respectively. However, none of the subjects transited to severe COVID-19 during the study or during the following clinical evaluation (21 more days). RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-2b, respectively. Elimination in HeberFERON treated patients was related to a significant increase in lymphocytes counts and also a significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recovered and had their laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, with the most frequent adverse event being headaches (17.4%). ConclusionsIn a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly eliminated the virus on day 4 of treatment when compared to treatment with IFN-2b alone. However, Heberon Alpha R alone also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impacted on the resolution of the symptoms. None of the patients developed severe COVID-19.

Enemas de factor de crecimiento epidérmico para inducir la remisión de la colitis ulcerosa izquierda / Epidermal growth factor enemas for induction of remission in left-sided ulcerative colitis

Introducción: la colitis ulcerosa es una enfermedad inflamatoria crónica de etiología poco conocida, que afecta la mucosa del colon. El efecto positivo del factor de crecimiento epidérmico fue reportado en estudio previo con uso de enema para tratamiento de la manifestación izquierda leve o moderada de la enfermedad. Este antecedente sirvió de base para evaluar la eficacia y perfil de seguridad de una solución viscosa del producto.Métodos: fueron aleatorizados 31 pacientes hacia tres grupos de tratamiento diario durante 14 días. Doce recibieron enemas de 10 mg de factor de crecimiento epidérmico en 100 mL de solución viscosa, mientras nueve fueron tratados con enemas placebo conteniendo solamente solución viscosa. Ambos grupos recibieron además 1,2 g diarios de mesalacina oral. El tercer grupo incluyó 10 pacientes con mesalacina en enemas de 3g / 100 mL. La variable principal de eficacia fue la respuesta clínica al finalizar las dos semanas de tratamiento, definida como la disminución de, al menos tres puntos, el índice basal de actividad de la enfermedad acompañada de mejoría endoscópica o histológica.Resultados: se alcanzó remisión de la enfermedad en todos los pacientes que recibieron factor de crecimiento epidérmico y en seis de los grupos mesalacina enema y placebo. Todas las comparaciones entre grupos mostraron superioridad estadísticamente significativa para el factor de crecimiento epidérmico, único producto que logró la reducción significativa del índice de actividad de la enfermedad y de la presencia e intensidad de los síntomas digestivos en los pacientes luego del tratamiento. Ningún evento adverso fue reportado.Conclusiones: estos resultados son consistentes con las anteriores evidencias moleculares y clínicas que señalan al factor de crecimiento...(AU)

Introduction: ulcerative colitis is a little known chronic inflammatory disease in colonic mucosa. The positive effect of epidermal growth factor was shown in a previous report, with enema use for treatment of mild to moderate left-sided manifestation of the disease. This evidence provided the basis for evaluating the efficacy and safety profile of a viscous solution of this product. Methods: thirty-one patients were randomized to three groups for daily medications during 14 days. Twelve received one 10 mg enema of epidermal growth factor dissolved in 100 mL of viscous solution whereas nine were treated with placebo enema; both groups also received 1.2 g of oral mesalamine per day. The other group included ten patients with 3 g / 100 mL of mesalamine enema. Primary end point was clinical responses after two weeks of treatment, defined as a decreased of, at least three points from baseline, the Disease Activity Index and endoscopic or histological evidences of improvement. Results: remission of disease was observed in all patients in the epidermal growth factor group, and six in both, mesalamine enema and placebo group. All the comparisons between groups showed statistically significant superiority for epidermal growth factor, the only product with significant reduction in disease activity index as well as the presence and intensity of digestive symptoms in patients after treatment. None adverse event was reported. Conclusions: the results agree with previous molecular and clinical evidences, indicating that the epidermal growth factor is effective to reduce disease activity and to induce remission. A new study involving more patients should be conducted to confirm the efficacy of the epidermal growth factor enemas(AU)

Enemas de factor de crecimiento epidérmico para inducir la remisión de la colitis ulcerosa izquierda / Epidermal growth factor enemas for induction of remission in left-sided ulcerative colitis

Introducción: la colitis ulcerosa es una enfermedad inflamatoria crónica de etiología poco conocida, que afecta la mucosa del colon. El efecto positivo del factor de crecimiento epidérmico fue reportado en estudio previo con uso de enema para tratamiento de la manifestación izquierda leve o moderada de la enfermedad. Este antecedente sirvió de base para evaluar la eficacia y perfil de seguridad de una solución viscosa del producto.Métodos: fueron aleatorizados 31 pacientes hacia tres grupos de tratamiento diario durante 14 días. Doce recibieron enemas de 10 mg de factor de crecimiento epidérmico en 100 mL de solución viscosa, mientras nueve fueron tratados con enemas placebo conteniendo solamente solución viscosa. Ambos grupos recibieron además 1,2 g diarios de mesalacina oral. El tercer grupo incluyó 10 pacientes con mesalacina en enemas de 3g / 100 mL. La variable principal de eficacia fue la respuesta clínica al finalizar las dos semanas de tratamiento, definida como la disminución de, al menos tres puntos, el índice basal de actividad de la enfermedad acompañada de mejoría endoscópica o histológica.Resultados: se alcanzó remisión de la enfermedad en todos los pacientes que recibieron factor de crecimiento epidérmico y en seis de los grupos mesalacina enema y placebo. Todas las comparaciones entre grupos mostraron superioridad estadísticamente significativa para el factor de crecimiento epidérmico, único producto que logró la reducción significativa del índice de actividad de la enfermedad y de la presencia e intensidad de los síntomas digestivos en los pacientes luego del tratamiento. Ningún evento adverso fue reportado.Conclusiones: estos resultados son consistentes con las anteriores evidencias moleculares y clínicas que señalan al factor de crecimiento...

Introduction: ulcerative colitis is a little known chronic inflammatory disease in colonic mucosa. The positive effect of epidermal growth factor was shown in a previous report, with enema use for treatment of mild to moderate left-sided manifestation of the disease. This evidence provided the basis for evaluating the efficacy and safety profile of a viscous solution of this product. Methods: thirty-one patients were randomized to three groups for daily medications during 14 days. Twelve received one 10 mg enema of epidermal growth factor dissolved in 100 mL of viscous solution whereas nine were treated with placebo enema; both groups also received 1.2 g of oral mesalamine per day. The other group included ten patients with 3 g / 100 mL of mesalamine enema. Primary end point was clinical responses after two weeks of treatment, defined as a decreased of, at least three points from baseline, the Disease Activity Index and endoscopic or histological evidences of improvement. Results: remission of disease was observed in all patients in the epidermal growth factor group, and six in both, mesalamine enema and placebo group. All the comparisons between groups showed statistically significant superiority for epidermal growth factor, the only product with significant reduction in disease activity index as well as the presence and intensity of digestive symptoms in patients after treatment. None adverse event was reported. Conclusions: the results agree with previous molecular and clinical evidences, indicating that the epidermal growth factor is effective to reduce disease activity and to induce remission. A new study involving more patients should be conducted to confirm the efficacy of the epidermal growth factor enemas

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

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

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

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

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

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

Pharmacokinetic and pharmacodynamic comparison of two "pegylated" interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study.

BACKGROUND: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG) results in a better pharmacokinetic profile and efficacy. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of a new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference, commercially available PEG-IFN alpha-2a in healthy male volunteers. METHODS: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 180 micrograms PEG-IFN alpha-2 dose was administered subcutaneously in both groups. Sixteen apparently healthy male subjects were included. Serum PEG-IFN concentration was measured during 336 hours by an enzyme immunoassay (EIA). Other clinical and laboratory variables were used as pharmacodynamic and safety criteria. RESULTS: The pharmacokinetic comparison by EIA yielded a high similitude between the formulations. In spite of a high subject variability, the parameters' mean were very close (in all cases p > 0.05): AUC: 53623 vs. 44311 pg.h/mL; Cmax: 333 vs. 271 pg/mL; Tmax: 54 vs. 55 h; half-life (t1/2): 72.4 vs. 64.8 h; terminal elimination rate (lambda): 0.011 vs. 0.014 h(-1); mean residence time (MRT): 135 vs. 123 h for reference and study preparations, respectively. There were no significant differences with respect to the pharmacodynamic variables either: serum neopterin and beta-2 microglobulin levels, stimulation of 2'5' oligoadenylate synthetase expression, and serum IFN antiviral activity. A strong Spearman's rank order correlation (p < 0.01) between the pharmacokinetic and pharmacodynamic concentration-time curves was observed. Both products caused similar leukocyte counts diminution and had similar safety profiles. The most frequent adverse reactions were leukopenia, fever, thrombocytopenia, transaminases increase and asthenia, mostly mild. CONCLUSIONS: Both formulations are fully comparable from the pharmacokinetic, pharmacodynamic, and safety profiles. Efficacy trials can be carried out to confirm clinical similarity.

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

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

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

Tolerancia del tratamiento con interferón estándar y ribavirina en pacientes cirróticos por virus de la hepatitis C / Tolerance to treatment with standard interferon and ribavirin in patients presenting with cirrhosis from hepatitis C

En el tratamiento de la cirrosis hepática compensada de etiología vírica la respuesta viral sostenida con el interferón y ribavirina es menor y se acompaña de mayor frecuencia e intensidad de efectos adversos en relación con pacientes no cirróticos. No obstante, dadas las pocas opciones terapéuticas para este grupo de pacientes y la necesidad de retrasar la aparición de las complicaciones, nos motivamos a la realización de este trabajo. Se presentan los resultados de un grupo de 36 pacientes con diagnóstico de cirrosis hepática por el virus de la hepatitis C (VHC) en estadio de Child A incluidos en un ensayo clínico multicéntrico, liderado por el Instituto de Gastroenterología, a los que se les administró un esquema terapéutico de interferón alfa-2b más ribavirina por 48 sem, se evaluó su tolerancia a través de los eventos adversos tantos clínicos como hematológicos. Los resultados demuestran que esta alternativa de tratamiento es segura y bien tolerada

In treatment of compensating hepatic cirrhosis of viral etiology the maintained viral response with Interferon and Ribavirin is minor and it is accompanied of a greater frequency of adverse effects in relation to non-cirrhotic patients. However, due to the scarce therapeutical options for this group of patients and the need to retard the appearance of complications, was the reason of present paper. Authors present the results from a group of 36 patients diagnosed with hepatic cirrhosis from HCV in A Child's stage included in multicenter clinical trials, sponsored by the Institute of Gastroenterology; patients received a therapeutical scheme of Interferon alfa-2b plus Ribavirin during 48 weeks assessing their tolerance by clinical and hematologic adverse events. Results demonstrate that this treatment alternative is safe and well-tolerated

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

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

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

Tolerancia del tratamiento con interferón estándar y ribavirina en pacientes cirróticos por virus de la hepatitis C / Tolerance to treatment with standard interferon and ribavirin in patients presenting with cirrhosis from hepatitis C

En el tratamiento de la cirrosis hepática compensada de etiología vírica la respuesta viral sostenida con el interferón y ribavirina es menor y se acompaña de mayor frecuencia e intensidad de efectos adversos en relación con pacientes no cirróticos. No obstante, dadas las pocas opciones terapéuticas para este grupo de pacientes y la necesidad de retrasar la aparición de las complicaciones, nos motivamos a la realización de este trabajo. Se presentan los resultados de un grupo de 36 pacientes con diagnóstico de cirrosis hepática por el virus de la hepatitis C (VHC) en estadio de Child A incluidos en un ensayo clínico multicéntrico, liderado por el Instituto de Gastroenterología, a los que se les administró un esquema terapéutico de interferón alfa-2b más ribavirina por 48 sem, se evaluó su tolerancia a través de los eventos adversos tantos clínicos como hematológicos. Los resultados demuestran que esta alternativa de tratamiento es segura y bien tolerada(AU)

In treatment of compensating hepatic cirrhosis of viral etiology the maintained viral response with Interferon and Ribavirin is minor and it is accompanied of a greater frequency of adverse effects in relation to non-cirrhotic patients. However, due to the scarce therapeutical options for this group of patients and the need to retard the appearance of complications, was the reason of present paper. Authors present the results from a group of 36 patients diagnosed with hepatic cirrhosis from HCV in A Child's stage included in multicenter clinical trials, sponsored by the Institute of Gastroenterology; patients received a therapeutical scheme of Interferon alfa-2b plus Ribavirin during 48 weeks assessing their tolerance by clinical and hematologic adverse events. Results demonstrate that this treatment alternative is safe and well-tolerated(AU)

Interferón gamma recombinante como alternativa terapéutica en niños con artritis idiopática juvenil / Recombinant gamma Interferon as a therapeutical alternative in children with juvenile idiopathic arthritis

INTRODUCCIÓN. La artritis idiopática juvenil (AIJ) es una enfermedad del colágeno caracterizada por sinovitis crónica y síntomas extraarticulares, de inicio antes de los 16 años de edad. El interferón gamma (INFγ) mostró eficacia en un ensayo anterior con pacientes resistentes o intolerantes a las otras terapias disponibles, por lo que se decidió evaluar su eficacia y seguridad como medicamento modificador de la evolución de esta enfermedad. MÉTODOS. Se realizó un ensayo clínico abierto, no controlado, en el que se administró INFγ por vía intramuscular en dosis de 50 000 UI/kg (hasta 1 x 10(6) UI) durante 2 años. En el ensayo se incluyeron 20 pacientes con AIJ: 5 tenían la forma pauciarticular; 9, la poliarticular y 6, la sistémica. RESULTADOS. Al final del tratamiento, 13 pacientes (65 por ciento) se evaluaron como respondedores. El número de articulaciones afectadas, los síntomas sistémicos y los valores de eritrosedimentación y del cuestionario de calidad se redujeron significativamente. Igualmente disminuyó el número de pacientes que continuó consumiendo esteroides, así como la dosis de éstos. El tratamiento fue bien tolerado, excepto en 2 pacientes. CONCLUSIONES. El INFγ disminuye la expresión de la quimiocina CCR-4 en los niños, pero no en los adultos con la enfermedad. Es posible concluir que esta citocina puede ser una alternativa terapéutica eficaz en pacientes con AIJ; para confirmarlo se necesitan estudios controlados más extensos

INTRODUCTION: The juvenile idiopathic arthritis (JIA) is a collagen entity characterized by chronic synovitis and extra-articulation symptoms appearing before the 16 years old. Gamma Interferon (gamma-INF) showed its effectiveness in a prior trial with resistant and intolerant patients to other available gamma-INF therapies, thus authors assessed its effectiveness and safety as a modifier drug of the course of this entity. METHODS: An open clinical, no-controlled trial was carried out administering gammaINF by intramuscular route in doses of 50 000 IU/kg (up to 1 x 10(6) IU) during two years. Trial included 20 patients with JIA: five had the pauciarticular type; nine had the polyarticular one and six had the systemic one. RESULTS: At treatment termination, 13 patients (65 percent) were assessed as respondents. Figure of involved joints, the systemic symptoms and the erythrosedimentation values, and the quality questionnaire significantly decreased, as well as the figure of patients to continue consuming steroids and its dosage. Treatment was well tolerated, except 2 patients. CONCLUSIONS: Gamma-INF decrease the expression of CCR-4 chemokine in children, but not in adults ones presenting this entity. We conclude that this cytokine may be an efficient therapeutical alternative in patients with JIA; for its confirmation it is necessary more extent controlled studies

Interferón gamma recombinante como alternativa terapéutica en niños con artritis idiopática juvenil / Recombinant gamma Interferon as a therapeutical alternative in children with juvenile idiopathic arthritis

INTRODUCCIÓN. La artritis idiopática juvenil (AIJ) es una enfermedad del colágeno caracterizada por sinovitis crónica y síntomas extraarticulares, de inicio antes de los 16 años de edad. El interferón gamma (INFγ) mostró eficacia en un ensayo anterior con pacientes resistentes o intolerantes a las otras terapias disponibles, por lo que se decidió evaluar su eficacia y seguridad como medicamento modificador de la evolución de esta enfermedad. MÉTODOS. Se realizó un ensayo clínico abierto, no controlado, en el que se administró INFγ por vía intramuscular en dosis de 50 000 UI/kg (hasta 1 x 10(6) UI) durante 2 años. En el ensayo se incluyeron 20 pacientes con AIJ: 5 tenían la forma pauciarticular; 9, la poliarticular y 6, la sistémica. RESULTADOS. Al final del tratamiento, 13 pacientes (65 por ciento) se evaluaron como respondedores. El número de articulaciones afectadas, los síntomas sistémicos y los valores de eritrosedimentación y del cuestionario de calidad se redujeron significativamente. Igualmente disminuyó el número de pacientes que continuó consumiendo esteroides, así como la dosis de éstos. El tratamiento fue bien tolerado, excepto en 2 pacientes. CONCLUSIONES. El INFγ disminuye la expresión de la quimiocina CCR-4 en los niños, pero no en los adultos con la enfermedad. Es posible concluir que esta citocina puede ser una alternativa terapéutica eficaz en pacientes con AIJ; para confirmarlo se necesitan estudios controlados más extensos(AU)

INTRODUCTION: The juvenile idiopathic arthritis (JIA) is a collagen entity characterized by chronic synovitis and extra-articulation symptoms appearing before the 16 years old. Gamma Interferon (gamma-INF) showed its effectiveness in a prior trial with resistant and intolerant patients to other available gamma-INF therapies, thus authors assessed its effectiveness and safety as a modifier drug of the course of this entity. METHODS: An open clinical, no-controlled trial was carried out administering gammaINF by intramuscular route in doses of 50 000 IU/kg (up to 1 x 10(6) IU) during two years. Trial included 20 patients with JIA: five had the pauciarticular type; nine had the polyarticular one and six had the systemic one. RESULTS: At treatment termination, 13 patients (65 percent) were assessed as respondents. Figure of involved joints, the systemic symptoms and the erythrosedimentation values, and the quality questionnaire significantly decreased, as well as the figure of patients to continue consuming steroids and its dosage. Treatment was well tolerated, except 2 patients. CONCLUSIONS: Gamma-INF decrease the expression of CCR-4 chemokine in children, but not in adults ones presenting this entity. We conclude that this cytokine may be an efficient therapeutical alternative in patients with JIA; for its confirmation it is necessary more extent controlled studies(AU)

[Extrahepatic manifestations of infection with hepatitis C virus]. / manifestaciones extrahepaticas de la infeccion por el virus de la hepatitis C.

Since the identification of hepatitis C in 1989, it has been studied extensively. In addition to its hepatotropic; have extrahepatic effects that are directly related to extrahepatic replication with high affinity to lymphoid tissues. As a result of that characteristics, autoimmune manifestations or a widespread immune stimulation, hematological, endocrine, dermatological, Ophtalmic, salival and other miscellaneous problems can be presented in affected patients.

Manifestaciones extrahepáticas de la infección por el virus de la hepatitis C / Extrahepatic manifestations of infection with hepatitis C virus

Desde su identificación en 1989 el virus de la Hepatitis C ha sido muy estudiado, encontrando que además de su acción hepatotrópica presenta efectos extrahepáticos que tienen una relación directa a su gran afinidad linfotrópica que genera manifestaciones de naturaleza autoinmune ó de extensa estimulación inmunitaria que dan manifestaciones hematológicas, endocrinas, renales, dermatológicas, oculares y otras diversas que se describen en esta revisión.

Since the identification of hepatitis C in 1989, it has been studied extensively. In addition to its hepatotropic; have extrahepatic effects that are directly related to extrahepatic replication with high affinity to lymphoid tissues. As a result of that characteristics, autoimmune manifestations or a wide spread immune stimulation, hematological, endocrine, dermatological, Ophtalmic, salival and other miscellaneous problems can be presented in affected patients.

Evaluación de la inmunogenicidad del interferon alfa 2b humano recombinante en pacientes con hepatitis crónica y hemangiomas de la infancia / Evaluation of the inmunogenicity of the human recombinant alfa2Brferonin patients who suffer of Haemangiomas and Hepatitis C since childhood

El interferón alfa 2b (IFN a-2b) humano recombinante, conocido como Heberon alfa R® es un fármaco con propiedades antivirales, antiproliferativas, antifibróticas e inmunomoduladoras que ha demostrado ser eficaz en el tratamiento de enfermedades virales, incluyendo las Hepatitis C y Hemangiomas, entre mútiples otras. En la actualidad, hay una enconada controversia en relación con el efecto que, sobre la eficacia del producto, puede tener el desarrollo de anticuerpos antiinterferón(AU)

Interferon alpha-2b as adjuvant treatment of recurrent respiratory papillomatosis in Cuba: National Programme (1994-1999 report).

Respiratory papillomatosis is a life-spoiling disease due to its high recurrence rate. Interferon (IFN)alpha-2b treatment, adjuvant to surgery, was assessed for its contribution to disease control and patient quality of life improvement. One hundred and sixty-nine patients (85 children and 84 adults) were included after surgical removal of the lesions followed by intramuscular IFN alpha-2b (Heberon alfa R, Heber Biotec), starting with 10(5) IU/Kg weight in children or 6 x 10(6) IU in adults, three times per week. The dose was reduced monthly, if no relapses occurred, until a monthly maintenance with 5 x 10(4) IU/Kgof weight in children or 3 x 10(6) IU in adults up to two years. In case of relapse, it was surgically removed and the patient returned to the higher dose level. The relapse frequency decreased significantly in 77 percent (69/90) of the recurrent patients both in children (34/46, 74 per cent) and adults (35/44, 79 per cent). Among patients included after their first papilloma, 67 per cent (44/66) had complete (no relapses) or partial (only one relapse) responses (children: 15/33, 45 per cent; adults 29/33, 88 per cent). One hundred and eighteen patients (73 per cent) concluded the treatment without lesions (children: 58 per cent; adults 82 per cent), while the rest showed a significant reduction in the number and size of lesions. IFN was well tolerated. Sixty-two patients (38 per cent) did not have adverse events. The main adverse reactions were fever (59 per cent), chills (24 per cent), arthralgias and myalgias (14 per cent) and headache (10 per cent). One patient developed anti-IFN alpha neutralizing antibodies and became resistant to treatment with recombinant IFN alpha-2b; he responded to natural leucocyte IFN alpha. Treatment with IFN alpha-2b, as an adjuvant to surgery represents a favourable and safe therapeutic alternative for patients with recurrent respiratory papillomatosis.