A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis

Introduction: Patients with primary biliary cholangitis (PBC) without biochemical response to ursodeoxycholic acid (UDCA) are at increased risk of liver-related mortality. Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual PPAR agonistic properties (α/γ). There is a strong mechanistic rationale for studying saroglitazar in PBC because PPARα is a molecular target of fibrates that showed improvements in liver tests in patients with PBC. Methods: In this 16-week, open-label, phase 3 study, 37 patients were screened across 3 clinical centers to enroll 7 patients. All patients received daily dose of saroglitazar 4 mg for 16 weeks in addition to their ongoing treatment with UDCA. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at week 16 as compared to baseline. Results: Mean age of the study population was 51.1 ± 10.0 years, all patients were female of Mexican descent, and mean body mass index was 25.5± = 4.8 kg/m2. Six (85.7%) patients reported taking ursodiol at baseline and continued throughout the study with a mean daily dosage of 417 mg. Among these, the daily dosage of UDCA 500 mg in 4 and 250 mg in 2 subjects, respectively. The mean baseline ALP level was 230 ± 103 U/L. The primary efficacy endpoint, mean change (reduction) from baseline in ALP concentration at week 16 based on the modified intent-to-treat population was -94 ± 53 U/L (P = 0.003), corresponding to a reduction of 48 ± 23%. Treatment with saroglitazar 4 mg resulted in a rapid and sustained decrease of ALP levels at week 4 (-84 ± 47 U/L, P = 0.003). Six patients who completed the study achieved mean ALP reduction of at least 40% at week 4 and all subsequent visits. Discussion: Although the study was terminated because of lack of enrollment, saroglitazar daily for 16 weeks resulted in rapid and sustained improvements in ALP with an acceptable safety profile in patients with PBC

ALTERACIONES EN EL METABOLISMO DE LA GLUCOSA E IMPACTO EN EL CURSO CLÍNICO DE LOS PACIENTES CON HEPATOPATÍA CRÓNICA Y CIRROSIS EN EL SERVICIO DE GASTROENTEROLOGÍA DEL CENTRO MÉDICO ISSEMYM

El 60% de los pacientes cirróticos presentan intolerancia a la glucosa y entre un 10% y 15% desarrollan diabetes hepatógena(DH). Esta asociación aumenta la fibrosis así como la presión portal (HP). Metodología: Estudio transversal comparativo retrospectivo ,del 01 agosto del 2014 al 31 de agosto 2015.Se efectuó un análisis univariado para la descripción de las características demográficas y clínicas de la muestra, se utilizaron frecuencias y porcentajes para las variables categóricas, medias y desviaciones estándar (DE) para las variables continuas. Como pruebas estadísticas se utilizó, chi-cuadrada para el contraste de variables categóricas y t de student a dos colas, para el contraste de variables continuas en muestras independientes. El nivel de significancia fue P ≤ 0.05. Resultados: El 16.15% (n=26) tenían diagnóstico de DM2, previo al diagnóstico de hepatopatía crónica. Se diagnosticó diabetes DH en el 27.95% (n=45 casos); 11.1% (n=5) HCSC y 88.9% (n=40) para pacientes con HCCC P=0.279. Se evaluó el índice de HOMA2 en 108 pacientes sin diagnóstico de DM2 previo, 13 pacientes presentaron HOMA1.5 y <2.5, y 42.59% (n=46) de pacientes tuvieron diagnóstico de resistencia a la insulina con un HOMA >2.6. Los pacientes con MAG y cirrosis presentaron con mayor frecuencia encefalopatía hepática 20.98% (n=30) p=0.031 y manifestaciones de HP 16.08% (n=23) con p= 0.0001. Conclusión : Las alteraciones en el metabolismo de la glucosa se asocian con mayor frecuencia a complicaciones de la enfermedad hepática crónica como encefalopatía, ascitis e hipertensión portal