Síndrome de Peutz-Jeghers, telangiectasias y prolapso de la válvula mitral. Presentación de caso y asesoramiento genético / Peutz-Jeghers syndrome, telangiectasias, and mitral valve prolapse. Case presentation and genetic counseling

Introducción: El síndrome de Peutz-Jeghers se caracteriza por hiperpigmentación mucocutánea y hamartomas gastrointestinales que pueden aparecer desde el estómago hasta el ano. Tiene un patrón de herencia autosómico dominante y expresividad variable. El diagnóstico se basa en los hallazgos clínicos y la apariencia histológica de los pólipos. No ha sido reportado hasta ahora asociación de esta entidad a telangiectasias y prolapso de la válvula mitral. Objetivo: Describir los hallazgos que permitieron establecer el diagnóstico de Síndrome de Peutz-Jeghers en un paciente y brindar asesoramiento genético. Presentación del caso: Paciente masculino de 36 años de edad con antecedentes de prolapso de la válvula mitral que acude a consulta de genética clínica con su esposa para solicitar asesoramiento genético, debido a que tienen una hija con diagnóstico de Síndrome de Peutz-Jeghers y desean conocer el riesgo de tener otro hijo afectado. Al examen físico se observa mácula hiperpigmentada en labio inferior y varias de estas en encías. Con tales hallazgos y el antecedente de tener la hija Síndrome de Peutz-Jeghers se emite el mismo diagnóstico en el padre. Como dato de interés se constatan en este individuo múltiples telangiectasias en tórax, cuello y espalda. Los estudios realizados en busca de la causa de estas fueron negativos. Conclusiones: Los antecedentes y los hallazgos encontrados en el paciente permitieron realizar el diagnóstico de Peutz-Jeghers y brindar asesoramiento genético. Se presenta el primer reporte de esta enfermedad asociada a telangiectasias y prolapso de la válvula mitral en la literatura científica(AU)

Introduction: Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and gastrointestinal hamartomas that can appear from the stomach to the anus. It has an autosomal dominant inheritance pattern and variable expressiveness. The diagnosis is based on clinical findings and histological appearance of the polyps. No association between this entity and telangiectasias and mitral valve prolapse has been reported so far. Objective: To describe the findings that made it possible to establish the diagnosis of Peutz-Jeghers syndrome in a patient and to provide genetic counseling. Case presentation: Thirty-six-year-old male patient with a history of mitral valve prolapse who attends a clinical genetics consultation with his wife to request genetic counseling due to the fact that their daughter was diagnosed with Peutz-Jeghers Syndrome and they want to know about the risk of having another affected child. On physical examination, a hyperpigmented macule on the lower lip and several of these on the gums were observed. With such findings and the antecedent of having a daughter with Peutz-Jeghers syndrome, the same diagnosis is made in the father. As data of interest, multiple telangiectasias on the thorax, neck and back were found in this individual. The studies carried out to identify the same cause were negative. Conclusions: The history and findings in this patient allowed us to make the diagnosis of Peutz-Jeghers syndrome as well as to provide genetic counselling. The first report of this disease associated with telangiectasias and mitral valve prolapse is presented in the scientific literature(AU)

Health-related quality of life in Cuban patients with chronic liver disease: A real-world experience.

INTRODUCTION AND OBJECTIVES: Patient-reported outcomes (PROs) are important for comprehensive assessment of chronic liver disease (CLD). Latin America and the Caribbean have a high burden of CLD, but PROs are lacking. We assessed health-related quality of life (HRQL) in Cuban patients with compensated CLD. MATERIALS AND METHODS: A cross sectional study performed of adult patients with a diagnosis of chronic viral infection B and C (HBV, HCV), non-alcoholic fatty liver diseases (NAFLD) and autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and overlap syndrome (AIH+PBC). PROs were collected using: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity-Specific Health Problem (WPAI: SHP), and the Chronic Liver Disease Questionnaire (CLDQ)-disease-specific. RESULTS: 543 patients enrolled, n=91 (HBV), n=188 (HCV), n=221 (NAFLD), n=43 (AILD). Of those with AILD, 22 had AIH, 14 PBC, and 7 overlap AIH/PBC. Mean age was 53.5 years, 64.1% female, 69.2% white, and 58.0% employed. Patients with HCV and AILD had more severe liver disease. A significant impairment in PROs was observed in HCV group whereas the AILD patients had more activity impairment. CLDQ-HRQL scores were significantly lower for patients with NAFLD and AILD compared to HBV. Male gender and exercising ≥90min/week predicted better HRQL. The strongest independent predictors of HRQL impairment were fatigue, abdominal pain, anxiety, and depression (p<0.05). CONCLUSIONS: HRQL for Cuban patients with compensated CLD differs according to the CLD etiology. Patients with HCV and AILD had the worst PRO scores most likely related to severe underlying liver disease and/or extrahepatic manifestations.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide.

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

Prospects for US-Cuba Cooperation in Gastroenterology, Hepatology and Liver Transplantation.

Gastroenterology, hepatology and liver transplant exchanges between the USA and Cuba have mainly consisted of scientific events and short visits. This has facilitated Cuba's inclusion in recognized scientific organizations, familiarity with Cuba's biotech products for treatment of liver disease, and access by Cuban professionals to the highest level of scientific information for clinical practice. It has also given health professionals in the US a more accurate picture of Cuba's health sector. The results of the Global Alcoholic Liver Disease Survey, which included Cuba and was designed and coordinated in the USA, opened doors to joint research and scientific publications. Until now, there have been no protocols for ongoing cooperation to enable bilateral clinical trials or continuing professional development in diagnostic, therapeutic and surgical techniques for hepatology and liver transplantation. There are many mutually beneficial research prospects in these areas. What has been accomplished to date, described in this article, is encouraging and sets the stage for future collaboration. KEYWORDS Hepatology, liver transplant, health, medicine, science, Cuba, USA.

Liver Stiffness Reference Values for Healthy Cuban Adults.

INTRODUCTION: Reference values for liver stiffness for healthy individuals vary worldwide. Different optimal cutoff values correspond to the stages of fibrosis in chronic liver disease. OBJECTIVES: Characterize the distribution of liver stiffness in Cuban adults without liver disease and its association with age, serum uric acid and body mass index. METHODS: A cross-sectional study was performed of 110 plasma donors recruited from the Havana Province Blood Bank January 2016 through February 2017. Measurements of liver stiffness were performed using a FibroScan elastography device on the same day of laboratory analyses and abdominal ultrasound. The Pearson coefficient was used to assess correlations, and the reference range was calculated using the mean and its 95% confidence interval. RESULTS: Liver stiffness values observed ranged from 2.2-6.3 kPa. The reference range (95% CI) for the 110 subjects without known liver disease was 4.2-4.6 kPa (mean 4.4). A positive correlation was observed between liver stiffness measurements and body mass index (r = 0.255, p ⟨0.01) and serum uric acid (r = 0.266, p ⟨0.01). There was no correlation between liver stiffness and age. Liver stiffness in women was similar to that of men, 4.3 (2.4-6.1) and 4.5 (2.2-6.3) kPa, respectively (p = 0.086). CONCLUSIONS: Liver stiffness in Cuban adults without liver disease ranges from 2.2-6.3 kPa. The reference range is 4.2-4.6 kPa. Body mass index and serum uric acid levels are positively associated with liver stiffness. CONTRIBUTION OF THIS RESEARCH: This is the first Cuban study using FibroScan to measure liver stiffness; its results will enable better assessment of liver disease in clinical practice.

Viusid, a nutritional supplement, increases survival and reduces disease progression in HCV-related decompensated cirrhosis: a randomised and controlled trial.

OBJECTIVES: Viusid is a nutritional supplement with recognised antioxidant and immunomodulatory properties which could have beneficial effects on cirrhosis-related clinical outcomes such as survival, disease progression and development of hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of viusid in patients with HCV-related decompensated cirrhosis. DESIGN: A randomised double-blind and placebo-controlled study was conducted in a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). The authors randomly assigned 100 patients with HCV-related decompensated cirrhosis to receive viusid (three oral sachets daily, n=50) or placebo (n=50) during 96 weeks. The primary outcome of the study was overall survival at 96 weeks, and the secondary outcomes included time to disease progression, time to HCC diagnosis, time to worsening of the prognostic scoring systems Child-Pugh and Model for End-Stage Liver Disease, and time to a new occurrence or relapse for each one of the main clinical complications secondary to portal hypertension at 96 weeks. RESULTS: Viusid led to a significant improvement in overall survival (90%) versus placebo (74%) (HR 0.27, 95% CI 0.08 to 0.92; p=0.036). A similar improvement in disease progression was seen in viusid-treated patients (28%), compared with placebo-treated patients (48%) (HR 0.47, 95% CI 0.22 to 0.89; p=0.044). However, the beneficial effects of viusid were wholly observed among patients with Child-Pugh classes B or C, but not among patients with Child-Pugh class A. The cumulative incidence of HCC was significantly reduced in patients treated with viusid (2%) as compared with placebo (12%) (HR 0.15, 95% CI 0.019 to 0.90; p=0.046). Viusid was well tolerated. CONCLUSIONS: The results indicate that treatment with viusid leads to a notable improvement in overall clinical outcomes such as survival, disease progression and development of HCC in patients with HCV-related decompensated cirrhosis. Trial registration number http://ClinicalTrials.gov (NCT00502086).

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)

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)

Evolución histórica de las terapias antivirales en hepatitis crónica C / Historical course of antiviral therapies in chronic hepatitis C

Dada la creciente incidencia y prevalencia de la infección crónica por el Virus de la hepatitis crónica C, con estimados de infección de alrededor del 3 por ciento de la población mundial, se realizó una revisión bibliográfica sobre los aspectos más relevantes de la evolución histórica que han experimentado las terapias antivirales utilizadas en el tratamiento de esta enfermedad. Se realizó una puesta al día sobre esta temática desde sus orígenes, con especial énfasis en las perspectivas futuras de esta terapéutica, actualmente en estudio por parte de la comunidad científica internacional. Para la realización de esta obra fueron consultadas 69 citas bibliográficas que incluyen metanálisis disponibles en MEDLINE desde 1998 hasta la actualidad, así como las publicaciones de los resultados de las investigaciones realizadas en nuestro país sobre este tema

A bibliographic review on the more significant features of historical course experienced by the antiviral therapies used in treatment of Chronic Hepatitis C virus was carried out due to the increasing incidence and prevalence of this disease with infection estimates about 3 percent of the world population. A updating was carried out on this subject matter from its origins with special emphasis on future perspectives of this therapeutics, nowadays under consideration by the international scientific community. For the carrying out of present work 69 bibliographic references were reviewed including the meta-analyses available in MEDLINE from 1998 up to present time, as well as the publications of researches results performed in our country on this subject

Evolución histórica de las terapias antivirales en hepatitis crónica C / Historical course of antiviral therapies in chronic hepatitis C

Dada la creciente incidencia y prevalencia de la infección crónica por el Virus de la hepatitis crónica C, con estimados de infección de alrededor del 3 por ciento de la población mundial, se realizó una revisión bibliográfica sobre los aspectos más relevantes de la evolución histórica que han experimentado las terapias antivirales utilizadas en el tratamiento de esta enfermedad. Se realizó una puesta al día sobre esta temática desde sus orígenes, con especial énfasis en las perspectivas futuras de esta terapéutica, actualmente en estudio por parte de la comunidad científica internacional. Para la realización de esta obra fueron consultadas 69 citas bibliográficas que incluyen metanálisis disponibles en MEDLINE desde 1998 hasta la actualidad, así como las publicaciones de los resultados de las investigaciones realizadas en nuestro país sobre este tema(AU)

A bibliographic review on the more significant features of historical course experienced by the antiviral therapies used in treatment of Chronic Hepatitis C virus was carried out due to the increasing incidence and prevalence of this disease with infection estimates about 3 percent of the world population. A updating was carried out on this subject matter from its origins with special emphasis on future perspectives of this therapeutics, nowadays under consideration by the international scientific community. For the carrying out of present work 69 bibliographic references were reviewed including the meta-analyses available in MEDLINE from 1998 up to present time, as well as the publications of researches results performed in our country on this subject(AU)

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

AIM: To investigate the capability of a biochemical and clinical model, BioCliM, in predicting the survival of cirrhotic patients. METHODS: We prospectively evaluated the survival of 172 cirrhotic patients. The model was constructed using clinical (ascites, encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model. It was applied to estimate 12-, 52- and 104-wk survival. The model¡¯s calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset. Finally, the model¡¯s validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk ¡Ü 8 and high risk > 8). RESULTS: In the validation cohort, all measures of fit, discrimination and calibration were improved when the biochemical and clinical model was used. The proposed model had better predictive values (c-statistic: 0.90, 0.91, 0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-, 52- and 104-wk mortality, respectively. In addition, the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L, 4.69) is better calibrated than MELD (H-L, 17.06) and CP (H-L, 14.23). There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk, P = 0.61; high risk, P = 0.77). CONCLUSION: Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients(AU)

Tratamiento prolongado con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo / Prolonged treatment with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B

Las tasas de seroconversión del antígeno e alcanzadas con los antivirales actuales no sobrepasan el 35 por ciento. La combinación de inmunomodulador y antiviviral ha sido teóricamente la estrategia más aceptada en los últimos años; sin embargo, los resultados en la práctica clínica han sido contradictorios. Se realizó el presente trabajo para evaluar la eficacia y seguridad de un esquema de tratamiento prolongado durante 52 sem con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo. Se estudiaron 46 pacientes asignados aleatoriamente: 23 recibieron 150 mg diarios de lamivudina por 4 sem, lamivudina más interferón alfa-2b (10 MU en días alternos) por 24 sem, seguido de lamivudina en la misma dosis y frecuencia hasta completar las 52 sem. Otros 23 recibieron 150 mg diarios de lamivudina por 4 sem y lamivudina más interferón alfa-2b (5 MU en días alternos) durante 52 sem. Se encontró que las tasas de seroconversión del antígeno fueron similares en ambos grupos. Una proporción significativa de pacientes con tratamiento combinado prolongado logró negativizar el ADN viral (52 por ciento frente al 26 por ciento, p=0,06) y el antígeno de superficie (48 por ciento frente al 26 por ciento, p=0,11), comparado con los controles. La mejoría en el índice de actividad histológica fue observada en el 48 por ciento de los pacientes tratados con tratamiento combinado prolongado frente al 22 por ciento de los controles (p=0,06). Se concluyó que el tratamiento prolongado de erferón y lamivudina durante 52 sem puede brindar beneficios clínicos en las tasas de pérdida sostenida del ADN viral, el antígeno de superficie y en el índice de actividad histológica (AU)

The seroconversion rates of e antigen attained with the current antivirals do not exceed 35 percent. The combination of immunomodulator and antiviral has been theoretically the most accepted strategy in the last five years; however, the results in clinical practice have been contradictory. This paper is aimed at evaluating the efficacy and security of a treatment scheme prolonged for 52 weeks with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B. 46 patients selected at random were studied: 23 received 150 mg of lamivudine daily during 4 weeks, lamivudine plus alpha-2b (10 MU every other day) for 24 weeks, followed by lamivudine in the same dose and frequency until completing the 52 weeks. Other 23 were administered 150 mg of lamivudine daily for 4 weeks plus alpha 2b interferon (5 MU every other day) during 52 weeks. It was found that the antigen seroconversion rates were similar in both groups. A marked proportion of patients with combined prolonged treatment proved to be negative to the viral DNA (52 percent vs. 26 p = 0.06) and the surface antigen (48 percent vs. 26 percent, p = 0.11) compared with the controls. The improvement in the histological activity rate was observed in 48 percent of the patients treated with combined prolonged treatment against 22 percent of the controls (p = 0.06) It was concluded that the prolonged treatment of interferon and lamivudine during 52 weeks may have clinical benefits on the rates of sustained viral DNA loss, surface antigen and the histological activity index (AU)

Tratamiento prolongado con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo / Prolonged treatment with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B

Las tasas de seroconversión del antígeno e alcanzadas con los antivirales actuales no sobrepasan el 35 por ciento. La combinación de inmunomodulador y antiviviral ha sido teóricamente la estrategia más aceptada en los últimos años; sin embargo, los resultados en la práctica clínica han sido contradictorios. Se realizó el presente trabajo para evaluar la eficacia y seguridad de un esquema de tratamiento prolongado durante 52 sem con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo. Se estudiaron 46 pacientes asignados aleatoriamente: 23 recibieron 150 mg diarios de lamivudina por 4 sem, lamivudina más interferón alfa-2b (10 MU en días alternos) por 24 sem, seguido de lamivudina en la misma dosis y frecuencia hasta completar las 52 sem. Otros 23 recibieron 150 mg diarios de lamivudina por 4 sem y lamivudina más interferón alfa-2b (5 MU en días alternos) durante 52 sem. Se encontró que las tasas de seroconversión del antígeno fueron similares en ambos grupos. Una proporción significativa de pacientes con tratamiento combinado prolongado logró negativizar el ADN viral (52 por ciento frente al 26 por ciento, p=0,06) y el antígeno de superficie (48 por ciento frente al 26 por ciento, p=0,11), comparado con los controles. La mejoría en el índice de actividad histológica fue observada en el 48 por ciento de los pacientes tratados con tratamiento combinado prolongado frente al 22 por ciento de los controles (p=0,06). Se concluyó que el tratamiento prolongado de erferón y lamivudina durante 52 sem puede brindar beneficios clínicos en las tasas de pérdida sostenida del ADN viral, el antígeno de superficie y en el índice de actividad histológica.

The seroconversion rates of e antigen attained with the current antivirals do not exceed 35 percent. The combination of immunomodulator and antiviral has been theoretically the most accepted strategy in the last five years; however, the results in clinical practice have been contradictory. This paper is aimed at evaluating the efficacy and security of a treatment scheme prolonged for 52 weeks with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B. 46 patients selected at random were studied: 23 received 150 mg of lamivudine daily during 4 weeks, lamivudine plus alpha-2b (10 MU every other day) for 24 weeks, followed by lamivudine in the same dose and frequency until completing the 52 weeks. Other 23 were administered 150 mg of lamivudine daily for 4 weeks plus alpha 2b interferon (5 MU every other day) during 52 weeks. It was found that the antigen seroconversion rates were similar in both groups. A marked proportion of patients with combined prolonged treatment proved to be negative to the viral DNA (52 percent vs. 26 p = 0.06) and the surface antigen (48 percent vs. 26 percent, p = 0.11) compared with the controls. The improvement in the histological activity rate was observed in 48 percent of the patients treated with combined prolonged treatment against 22 percent of the controls (p = 0.06) It was concluded that the prolonged treatment of interferon and lamivudine during 52 weeks may have clinical benefits on the rates of sustained viral DNA loss, surface antigen and the histological activity index.

Hígado graso: enfoque diagnóstico y terapéutico / Fatty liver. Diagnostic and therapeutic approach

El enfoque diagnóstico y terapéutico propuesto en esta revisión sobre hígado graso se hizo en función de las necesidades del médico práctico. Se planteó una disquisición teórica sobre el problema terminológico de este síndrome y se abordaron los mecanismos patogénicos comunes en las diferentes condiciones clínicas que predisponen a padecer este problema de salud que puede presentarse como una simple esteatosis hepática, pero también puede llegar a ser causa de una cirrosis hepática que conduzca al paciente a un transplante hepático. Se consideró la importancia de sopesar la suma de factores que predisponen a la enfermedad, los estudios imagenológicos y marcadores de riesgo de desarrollo de fibrosis antes de indicar la biopsia hepática. El tratamiento va dirigido a disminuir el flujo de ácidos grasos al hígado, proteger al hepatocito de mecanismos oxidativos, evitar tóxicos conocidos que dañen al hígado y tratar los factores condicionantes o asociados. Se propuso un algoritmo de atención y seguimiento de estos enfermos(AU)

Hígado graso: enfoque diagnóstico y terapéutico / Fatty liver. Diagnostic and therapeutic approach

El enfoque diagnóstico y terapéutico propuesto en esta revisión sobre hígado graso se hizo en función de las necesidades del médico práctico. Se planteó una disquisición teórica sobre el problema terminológico de este síndrome y se abordaron los mecanismos patogénicos comunes en las diferentes condiciones clínicas que predisponen a padecer este problema de salud que puede presentarse como una simple esteatosis hepática, pero también puede llegar a ser causa de una cirrosis hepática que conduzca al paciente a un transplante hepático. Se consideró la importancia de sopesar la suma de factores que predisponen a la enfermedad, los estudios imagenológicos y marcadores de riesgo de desarrollo de fibrosis antes de indicar la biopsia hepática. El tratamiento va dirigido a disminuir el flujo de ácidos grasos al hígado, proteger al hepatocito de mecanismos oxidativos, evitar tóxicos conocidos que dañen al hígado y tratar los factores condicionantes o asociados. Se propuso un algoritmo de atención y seguimiento de estos enfermos.