Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation

Abstract

The role of ursodeoxycholic acid (UDCA) in the prevention of hepatic complications after allogeneic stem cell transplantation was studied in a prospective randomized open-label multicenter trial. A total of 242 patients were allocated to receive (n ‫؍‬ 123) or not to receive (n ‫؍‬ 119) UDCA in the dose of 12 mg/kg/d orally from the day preceding the conditioning until day 90 after transplantation. In the UDCA-treated group a significantly smaller proportion of patients developed a serum bilirubin level exceeding 50 M (18 of 123 versus 31 of 119, P ‫؍‬ .04), and similarly a smaller proportion of patients exceeded the alanine aminotransferase level of 100 U/L. There was no difference in the incidence of veno-occlusive disease of the liver. Compared to the control group, in the UDCA-treated group there was a nonsignificant trend toward a lower overall incidence of acute graft-versushost disease (GVHD) and a significantly lower incidence of grade III to IV acute GVHD (5 of 123 versus 17 of 119, P ‫؍‬ .01), stage II to IV liver and intestinal GVHD, and stage III to IV skin GVHD. There was no difference in the incidence of chronic GVHD or in the relapse rate. Among the patients given UDCA, the survival at 1 year was significantly better, 71% versus 55% (P ‫؍‬ .02), and the nonrelapse mortality rate was lower, 19% versus 34% (P ‫؍‬ .01), than in the control group. There were significantly more deaths in GVHD in the control group. In conclusion, UDCA administration reduced hepatic problems and severe acute GVHD and improved survival. These results suggest a role for UDCA in the prevention of transplantrelated complications in allogeneic transplantation.

Risk factors for hepatic veno-occlusive disease: a retrospective unicentric study in 116 children autografted after a high-dose BU-thiotepa regimen

“…[24][25][26][27][28] In this population, neither heparin, nor ursodexosycholic acid administration appeared to minimize the risk of HVOD compared to that reported in other series. However, in the present series these drugs were not prospectively evaluated by randomization.…”

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

“…A randomized prospective clinical trial in adult patients receiving myeloablative conditioning found that SCT recipients treated with ursodeoxycholic acid during the early phase after transplantation had lower risk of liver injury, aGVHD and NRM than patients not receiving ursodeoxycholic acid. 43 However, another randomized study did not find any survival benefit of the combination of heparin and ursodeoxycholic acid compared with heparin alone. 44 More recently, a meta-analysis including 824 patients from 6 studies showed a lower risk of VOD and NRM in patients receiving ursodeoxycholic acid.…”

Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation

“…Patients with hepatic cGVHD meeting the following criteria were entered into this study: ALP or g-GTP elevated more than twice the upper normal limits and improved less than 10% by UDCA and immunosuppressants (PSL and/or CsA); negative for anti-hepatitis C virus antibody, hepatitis B virus surface antigen and CMV antigen; no evidence of non-alcoholic fatty liver disease and other biliary tract diseases on ultrasonography and/or computerized tomography (CT). Furthermore, 12 patients (non-BF group) treated without BF from 1997 to 2000 in our hospital were selected retrospectively so that they were age and sex matched with the BF group (Table 1, patients [11][12][13][14][15][16][17][18][19][20][21][22].…”

“…A recent report of a large, randomized, multicenter trial revealed that prophylactic UDCA administration was effective in preventing severe acute GVHD after allo-SCT and improved survival, 11 but there was no difference in cGVHD. Chronic nonsuppurative destructive cholangitis is a common pathological feature of cGVHD and PBC, 16 where the bile duct epithelial cells are the targets of immunological injury.…”

“…[7][8][9] Ursodeoxycholic acid (UDCA), which is widely accepted as the standard medical treatment with documented efficacy, 10 is also used for the treatment of cGVHD of the liver, along with corticosteroids and calcineurin inhibitors. 11 Although UDCA has been reported to reduce hepatic complications after allo-SCT and improve survival, there are still a considerable number of patients with cGVHD who are resistant to UDCA. 4 Bezafibrate (BF), which is a widely used agent for hyperlipidemia, has been used in the treatment of PBC patients.…”