Abstract
Background: Hepatic sinusoidal obstruction syndrome (HSOS) is a serious life-threatening complication of hematopoietic stem cell transplantation (HSCT). Currently, there is no optimal therapeutic strategy and preventive measures are ill-defined. Ursodeoxycholic acid (UA) is well-tolerated, inexpensive oral medication that has been associated with possible benefit as a prophylactic agent. We sought to summarize and quantify the clinical effects of prophylactic ursodeoxycholic acid in the context of HSCT. We undertook a systematic review of studies addressing the use of UA as monotherapy or in combination with other agents in patients undergoing HSCT.
Methods: The Search Strategy included MEDLINE (1966 to 4th week of March 2006), EMBASE (1980 to 4th week of March 2006), all EBM Reviews (4th quarter of 2005), Ovid Healthstar (1966 to 4th week of March 2006) and Google Scholar on March 20/2006. A random effects model was used to summarize outcome data.
Results: Six studies representing 824 patients were included in the review; 4 randomized clinical trials and 2 historical controlled studies. Three randomized clinical trials comparing prophylactic UA to no treatment demonstrated reduced proportion of HSOS (Relative Risk (RR) 0.34; 95% CI 0.17–0.66). When limited to higher quality studies, the effects remain (RR 0.36; 95%CI 0.15–0.90). Transplant related mortality also appears to be reduced (RR 0.58; 95% CI 0.35–0.95. However, UA did not significantly improve the outcomes of acute graft versus host disease (RR 0.76; 95% CI 0.53–1.09), relapse (RR 0.77; 95% CI 0.46–1.31) or overall survival (RR 1.22; 95 % CI 0.96–1.54).
Conclusion: UA is effective for HSOS prophylaxis in patients undergoing HSCT. HSCT centers should consider UA as standard therapy and controlled trials of novel treatments for HSOS should consider the use of UA as a comparator.
Soluble Thrombomodulin Attenuates Endothelial Cell Damage in Hepatic Sinusoidal Obstruction Syndrome
