Mecanismos de acción y aplicaciones terapéuticas del ácido ursodeoxicólico en las enfermedades hepáticas colestásicas / Potential mechanisms of action and therapeutic applications of the ursodeoxycholic acid in cholestasis

El ácido ursodeoxicólico es un ácido biliar hidrofílico, que representa una pequeña fracción del pool de ácidos biliares. En las dos últimas décadas, numerosas enfermedades hepáticas colestásicas crónicas (cirrosis biliar primaria, colangitis esclerosante primaria, colestasia intrahepática del embarazo) han sido tratadas con AUDC. Sin embargo, hasta hoy su eficacia sólo ha sido demostrada en la cirrosis biliar primaria, siendo necesario realizar estudios que permitan definir claramente sus indicaciones. Su efecto es mediado por una disminución del daño de los ácidos biliares tóxicos retenidos sobre la membrana celular de los hepatocitos, a través de una estimulación de la secreción biliar, mejoría del flujo biliar y disminución del daño hepático mediado por el sistema inmune

Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment

Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt-PA may alter the natural course of VOD.