RESUMEN
The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2 ) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, -3.8 to 7.0 mm Hg) and those allocated to placebo (-2.4 mm Hg; IQR, -4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.
Asunto(s)
Síndrome Hepatopulmonar/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Calidad de Vida , Sorafenib/administración & dosificación , Biomarcadores/sangre , Método Doble Ciego , Ecocardiografía , Femenino , Síndrome Hepatopulmonar/sangre , Síndrome Hepatopulmonar/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neovascularización Patológica/diagnóstico , Placebos/administración & dosificación , Placebos/efectos adversos , Prueba de Estudio Conceptual , Inhibidores de Proteínas Quinasas/efectos adversos , Sorafenib/efectos adversos , Resultado del TratamientoRESUMEN
AIM: To study the effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome. METHODS: Garlic powder in a capsule form was given to 15 children with hepatopulmonary syndrome (confirmed by contrast echocardiography) at the dosage of 1 g/1.73 m(2) per day. Patients were evaluated clinically and by arterial blood gas every four weeks. RESULTS: The garlic capsule was administered to 15 patients with hepatopulmonary syndrome. There were 10 boys and 5 girls with a mean age of 9.4+/-3.9 years. The underlying problems were biliary tract atresia (4 patients), autoimmune hepatitis (4 patients), cryptogenic cirrhosis (4 patients) and presinusoidal portal hypertension (3 patients). Eight patients(53.3%) showed an increase of 10 mmHg in their mean arterial oxygen pressure. The baseline PaO(2) was 65.6+/-12.1 mmHg in the responder group and 47.1+/-11.2 mmHg in non-responder group. At the end of treatment the mean PaO(2) in responders and non-responders was 92.2+/-7.75 mmHg and 47.5+/-11.87 mmHg, respectively (P<0.01). CONCLUSION: Garlic may increase oxygenation and improve dyspnea in children with hepatopulmonary syndrome.