Removal of Bile Acids by Two Different Extracorporeal Liver Support Systems in Acute-on-Chronic Liver Failure

Abstract

Acute-on-chronic liver failure (ACLF) is accompanied by marked intrahepatic cholestasis leading to accumulation of cytotoxic bile acids. Extracorporeal liver support systems efficiently remove bile acids, but their effect on bile acid composition in ACLF is unknown. The aim of the present study was to compare elimination of individual plasma bile acids by albumin dialysis (Molecular Adsorbents Recirculating System, MARS) and fractionated plasma separation (Prometheus). Eight consecutive patients with ACLF underwent alternating 6-hour sessions with MARS or Prometheus in a randomized, cross-over design. Serum samples were obtained before, during, and after each treatment, and individual bile acids including cholic acid and chenodeoxycholic acid (CDCA) were measured by gas chromatography. MARS and Prometheus removed total bile acids to a similar extent (reduction ratio, 45% and 46%, respectively). Both devices cleared cholic acid more efficiently than did CDCA. The molar fraction of CDCA (fCDCA) was elevated at baseline and correlated with the degree of liver dysfunction. Prometheus but not MARS treatments further increased fCDCA. Although both devices eliminate total bile acids to a similar extent, clearance of individual bile acids is different, leading to a slight change of the bile acid profile toward hydrophobic bile acids during Prometheus treatments.

An evaluation of the usefulness of extracorporeal liver support techniques in patients with severe liver dysfunction

“…However, only MARS has been shown to significantly attenuate hyperdynamic circulation in patients with ACLF [7,34,35].…”

Acute-on-chronic liver failure: extracorporeal liver assist devices

“…Clinically, cholestasis presents with pruritis, renal and pulmonary vascular injury, and hemodynamic changes. Multiple studies have demonstrated the efficacy of albumin dialysis in decreasing total bile acid pool and bilirubin concentration, providing relief of the clinical manifestations of cholestasis [43,44]. MARS treatment could be a useful tool in facilitating hepatic recovery in patients with severe drug-induced liver injury with features of cholestasis, posttransplant cholestasis due to graft dysfunction, and in liver failure patients awaiting transplantation [45,46,47 ].…”

Evaluación de los sistemas de soporte hepático extracorpóreo en el tratamiento de la insuficiencia hepática. Revisión sistemática

“…Once estudios evaluaron el sistema Prometheus s : 6 eran series de casos 23-28 y el resto, ensayos clínicos aleatorizados 15,17,[29][30][31] . No se localizaron estudios que evaluasen la técnica de soporte hepático Prometheus s desde un punto de vista económico.…”

“…La prueba de Dersimonian y Laird no mostró evidencia estadística de heterogeneidad (p ¼ 0,1749), y también se observó una reducción no estadísticamente significativa (RR de 0,75 [IC 95% de 0,42-1,35]; p ¼ 0,3427).Sistema Prometheus sLos resultados sobre la supervivencia de los pacientes tratados con el sistema Prometheus s pueden verse en la tabla 3. De los ensayos aleatorizados incluidos, 3 de ellos eran de diseño cruzado y utilizaron los mismos pacientes[29][30][31] . En los 2 ensayos en los que se utilizó grupo control, no se encontraron diferencias significativas en la supervivencia de los diferentes grupos15,17 .Aspectos de seguridadEn varios de los estudios incluidos en esta revisión no se mencionan efectos adversos, y en los que sí lo hacen, parecen ser similares a los del grupo control, con excepción de la trombocitopenia y la hemorragia, que parecen verse incrementadas con el sistema MARS s .…”