Bevacizumab for treating Hereditary Hemorrhagic Telangiectasia patients with severe hepatic involvement or refractory anemia.

OBJECTIVE: To report our clinical experience with bevacizumab in a cohort of Hereditary Hemorrhagic Telangiectasia (HHT) patients with severe hepatic involvement and/or refractory anemia. METHODS: Observational, ambispective study of the Institutional Registry of HHT at Hospital Italiano de Buenos Aires. Patients were treated with bevacizumab due to iron deficiency refractory anemia secondary to nasal/gastrointestinal bleeding and/or high output cardiac failure. We describe basal clinical data, bevacizumab schedules, efficacy outcomes and adverse events. Wilcoxon signed ranks test and longitudinal analysis were conducted. RESULTS: Twenty adult patients were included from July 2013 to June 2019. Clinical indications were: 13 for anemia, 4 for heart failure and 3 for both. In the anemia group, median pretreatment hemoglobin was 8.1 g/dl [IQR: 7.2-8.4] and median transfusion requirement was 4 units [2-6]. In heart failure group, pretreatment median cardiac index was 4.5 L/min/m2 [4.1-5.6] and cardiac output was 8.3 L/min [7.5-9.2]. Bevacizumab 5 mg/kg/dose every 2 weeks for 6 applications was scheduled. By the end of induction, median hemoglobin at 3 months was 10.9 g/dl [9.5-12.8] (p = 0.01) and median transfusion requirement 0 units [0-1] (p<0.01), and this effect was more or less sustained during a year. Regarding heart failure group, two patients had complete hemodynamic response and achieved liver transplantation and two had partial response. No serious adverse events were registered. CONCLUSION: Bevacizumab is a promising line of treatment for HHT patients with refractory anemia. For patients with high output cardiac failure, bevacizumab may be useful as bridge therapy awaiting for liver transplantation.

[The Argentine experience with human immune deficiency virus positive patients in the waiting list for liver transplantation: preliminary analysis]. / Experiencia argentina con pacientes positivos para el virus de la inmunodeficiencia humana en lista de espera para trasplante hepático: análisis preliminar.

UNLABELLED: After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. OBJECTIVE: To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. PATIENTS AND METHODS: We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. RESULTS: The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 1615 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27%) vs 61 (18.7%) (P < 0.05), cadaveric donor transplant 10 (13%) vs 95 (29.4%) (P < 0.001), living donor transplant 0 (0%) vs 5 (1.1%) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). CONCLUSION: HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.

Experiencia argentina con pacientes positivos para el virus de la inmunodeficiencia humana en lista de espera para trasplante hepático: análisis preliminar / [The Argentine experience with human immune deficiency virus positive patients in the waiting list for liver transplantation: preliminary analysis].

UNLABELLED: After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. OBJECTIVE: To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. PATIENTS AND METHODS: We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. RESULTS: The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 1615 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27

) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). CONCLUSION: HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.

Experiencia argentina con pacientes positivos para el virus de la inmunodeficiencia humana en lista de espera para trasplante hepático: análisis preliminar. / [The Argentine experience with human immune deficiency virus positive patients in the waiting list for liver transplantation: preliminary analysis].

UNLABELLED: After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. OBJECTIVE: To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. PATIENTS AND METHODS: We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. RESULTS: The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 1615 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27

) vs 61 (18.7

) (P < 0.05), cadaveric donor transplant 10 (13

) vs 95 (29.4

) (P < 0.001), living donor transplant 0 (0

) vs 5 (1.1

) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). CONCLUSION: HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.

[Transient elastography: noninvasive assessment of liver fibrosis. Report of 1,000 cases in Argentina]. / Elastometría transicional: medición no invasiva de la fibrosis hepática. Reporte de 1.000 casos en Argentina.

BACKGROUND: Transient elastography (TE) is a noninvasive method for assessment of hepatic fibrosis. OBJECTIVE: To present the first case series evaluated in Latin America, in an University Hospital in Buenos Aires, during an 18-month period. METHODS: Data was collected between August 2009 and January 2011. A database was built considering clinical, biochemical and histology data. The exams were performed with a medium probe. An exam was considered valid when success rate was higher than 60% and interquartile range lower than 30%. RESULTS: 1,023 studies were performed. Patients were referred by in-hospital (53%) and out-hospital physicians (47%). Etiologies were: HCV 409 (40%), NAFLD 213 (20.8%), HBV 110 (10.7%), cholestasis 93 (9.1%), other 198 (19.4%). Significant fibrosis (F > 2) was detected in 32.4% HCV, 32.1% HBV 31.5% NASH, and 33.4% cholestasis. Exams were not technically achievable in 29 patients (2.8%), of whom 96.5% had body mass index (BMI) higher than 28 kg/m2. However 117 of 145 patients with BMI higher than 28 kg/m2 had a successful exam. In 332 patients simultaneously biopsies (less than 6 months) were obtained, with overall coincidence of 77%. In 21 HCV transplanted patients coincidence was 90.4%. CONCLUSION: Similar results to those in the literature were obtained, with excellent biopsy correlation in HCV transplanted patients. The increasing use of TE in the assessment and monitoring of chronic liver diseases has become evident by both increasing number of exams and decreasing number of diffuse liver biopsies.

[Diagnosis, treatment and evolution of the Budd-Chiari syndrome: a single center experience]. / Diagnóstico, tratamiento y evolución del síndrome de Budd-Chiari: experiencia de un centro.

INTRODUCTION: The Budd-Chiari syndrome is a low-prevalence disease due to an hepatic outflow obstruction. It is associated with procoagulant status and liver transplantation is one of the therapeutic tools for the treatment. OBJECTIVE: To evaluate the etiology, presenting form, treatment and evolution of patients with Budd-Chiari syndrome. PATIENTS AND METHOD: Ten consecutive adult patients with Budd-Chiari syndrome evaluated from January 1998 to June 2009 were prospectively included. The median follow up was 32.4 months (4-108 months). RESULTS: The mean age of patients was 34 +/- 12 years old. Presentation was acute in 1 patient, chronic in 2 and subacute in 7. The mean time from consultation to diagnosis was 4 +/- 2 days. Clinical manifestations were splenomegaly in 8 patients, malnutrition in 7, ascites in 6 and encephalopathy in 4. Diagnosis was confirmed by angiography in all cases. Initial prothrombin concentration was < 30% in 3 patients, 31% to 50% in 5, and > 50% in 2; hematocrit was > 45% in 5 patients and platelet count was > 400.000/mm3 in 6. MELD distribution at diagnosis was < or = 13 points in 4 patients, between 14 and 16 points in 5 and > or = 17 points in 1. Policytemia vera was detected in 7 patients, essential thrombocythemia in 1 and positive lupus inhibitor in 4. Nine patients were anticoagulated after diagnosis. Angioplasthy was required in 1 patient and 6 were treated with a transjugular intrahepatic portosystemic shunt. Death occurred in 1 patient due to gastrointestinal bleeding. Two patients were transplanted. CONCLUSION: In our experience all patients with Budd-Chiari syndrome have a procoagulant status. The transjugular intrahepatic portosystemic shunt is effective in treating this syndrome and liver transplantation should be reserved for patients who are refractory to other therapeutics.

[Twenty-four weeks therapy with peginterferon alfa-2a could be similar to 48 weeks therapy in patients with HBeAg positive chronic hepatitis B and good predictors of response: results of a pilot study]. / El tratamiento de 24 semanas con PEG interferón alfa 2a podría ser similar al de 48 semanas en pacientes con hepatitis B crónica HBeAg positivo y buenos predictores de respuesta: resultados de un estudio piloto.

BACKGROUND: 48 week therapy with peginterferon alfa-2a has demonstrated to be effective in about one third of patients with HBeAg-positive chronic hepatitis B. Although the recommended treatment duration for these patients is 48 weeks, there are no enough data supporting 48 weeks of therapy over 24 weeks of therapy. Treatment might be shortened particularly in patients with good predictors of response. AIM: To compare the efficacy of 48 weeks vs 24 weeks of therapy with peginterferon alfa-2a, in patients with chronic hepatitis B who had good predictors of response. PATIENTS AND METHODS: Nineteen patients with high baseline ALT levels (> 3 ULN) and low viral load (HBV DNA < 10(9) copies/ml) were treated with peginterferon alfa-2a 180 mcg/week, during 48 weeks. Virological, biochemical and serological responses were compared with those obtained in 16 patients with similar baseline characteristics treated with peginterferon alfa-2a for 24 weeks. All patients had a followup period of 24 weeks after the end of therapy. RESULTS: At end of follow-up, HBeAg seroconversion was observed in 7/19 (36.8%) of patients treated for 48 weeks and in 6/16 (37.5%) of patients treated for 24 weeks (NS). Patients treated for 48 weeks evidenced a significantly higher decrease in HBV DNA at the end of therapy than patients treated for 24 weeks (-4.8 logs vs -3.6 logs respectively, p < 0.05). However, the percentage of patients with HBV DNA < 100.000 copies/ml was similar in both groups at the end of follow up (42.1% vs 43.7%, NS). No significant differences between both groups were observed regarding ALT normalization, HBsAg loss or seroconversion. The incidence of aderse events was similar in both groups. CONCLUSION: The results from this pilot study indicate that 24 weeks of therapy with peginterferon alfa-2a could be similar to 48 weeks therapy in patients with HBeAg positive chronic hepatitis B who have good predictors of response.

La dexametasona, un inhibidor de la expresion de la oxido nitrico sintasa inducible, no modifica el estado hiperdinamico en ratas cirroticas / Dexamethasone, an inhibitor of the expression of the inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats

El aumento de la producción de óxido nítrico juega un papel importante en la fisiopatología de la cir- culación hiperdinámica asociada a la hipertensión portal. El probable mecanismo por el cual se produce este aumento no se encuentra aún bien definido. Con el objetivo de evaluar si la isoforma inducible es la responsable de estos cambios hemodinámicos, hemos estudiado el efecto de la administración de dexametasona, un inhibidor de la expresión de la óxido nítrico sintasa II, en ratas cirróticas tras la ligadura y sección del colédoco. Se determinaron los diferentes parámetros hemodinámicos sistémicos y esplácnicos, mediante la técnica de microesferas radiactivas, luego de la administración de dexametasona (3 mg/kg/día durante 3 días, ip) o su vehículo. En los animales cirróticos el efecto glucocorticoideo se puso de manifiesto a través de una disminución significativa en la ganancia de peso corporal y un moderado aumento, pero no significativo, de la presión arterial media. La administración de dexametasona no se asoció a cambios significativos de la resistencia vascular sistémica y esplácnica como así tampoco del flujo sanguíneo portal y presión portal. Similares resultados se observaron en el grupo de animales utilizados como controles. Se detectaron niveles significativamente más elevados de endotoxina en sangre portal y sistémica en 5 de 6 animales cirróticos. Nuestros resultados muestran que la administración de dexametasona no modifica los parámetros hemodinámicos sistémicos y esplácnicos en ratas cirróticas y endotoxémicas sugiriendo que la estimulación de la sintasa inducible no juega un papel importante en el aumento de la síntesis de óxido nítrico en la cirrosis.

La dexametasona, un inhibidor de la expresion de la oxido nitrico sintasa inducible, no modifica el estado hiperdinamico en ratas cirroticas / Dexamethasone, an inhibitor of the expression of the inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats

El aumento de la producción de óxido nítrico juega un papel importante en la fisiopatología de la cir- culación hiperdinámica asociada a la hipertensión portal. El probable mecanismo por el cual se produce este aumento no se encuentra aún bien definido. Con el objetivo de evaluar si la isoforma inducible es la responsable de estos cambios hemodinámicos, hemos estudiado el efecto de la administración de dexametasona, un inhibidor de la expresión de la óxido nítrico sintasa II, en ratas cirróticas tras la ligadura y sección del colédoco. Se determinaron los diferentes parámetros hemodinámicos sistémicos y esplácnicos, mediante la técnica de microesferas radiactivas, luego de la administración de dexametasona (3 mg/kg/día durante 3 días, ip) o su vehículo. En los animales cirróticos el efecto glucocorticoideo se puso de manifiesto a través de una disminución significativa en la ganancia de peso corporal y un moderado aumento, pero no significativo, de la presión arterial media. La administración de dexametasona no se asoció a cambios significativos de la resistencia vascular sistémica y esplácnica como así tampoco del flujo sanguíneo portal y presión portal. Similares resultados se observaron en el grupo de animales utilizados como controles. Se detectaron niveles significativamente más elevados de endotoxina en sangre portal y sistémica en 5 de 6 animales cirróticos. Nuestros resultados muestran que la administración de dexametasona no modifica los parámetros hemodinámicos sistémicos y esplácnicos en ratas cirróticas y endotoxémicas sugiriendo que la estimulación de la sintasa inducible no juega un papel importante en el aumento de la síntesis de óxido nítrico en la cirrosis. (AU)