Ursodiol prophylaxis against hepatic veno-occlusive disease in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis
Year: 2006
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Hepatic veno-occlusive disease (VOD) is a well-recognized complication of hematopoietic stem cell transplantation (HSCT). Ursodiol has been studied as a prophylactic agent against this condition with varying success. We performed a systematic review and meta-analysis of the existing literature to assess the effectiveness of ursodiol in preventing VOD in patients undergoing HSCT. We conducted computerized and hand searches of ursodiol, hepatic VOD, and variations of the two terms. We then selected those randomized trials and observational studies which compared the incidence of VOD in HSCT patients receiving ursodiol versus control. The outcome data from the eligible studies were pooled and summarized (Table 1). We also preformed an a priori subgroup analysis based on study type (observational vs randomized clinical trial), type of conditioning regimen used (busulfan vs total body irradiation based), time from ursodiol initiation to transplant, type of transplant (allogeneic vs autologous) and different diagnostic criteria for VOD (Seattle criteria vs modified Seattle criteria. Overall, we found that ursodiol prophylaxis decreased the risk of VOD (pooled OR 0.33, 95% CI 0.12, 0.90). All subgroups showed benefited from ursodiol use; however wide confidence intervals indicate imprecision in the estimate of this benefit. Also, there was no statistically significant difference in survival when comparing subgroups: clinical trial versus observational study, P = .89; busulfan vs total body irradiation, P = .64; Seattle versus modified Seattle criteria, P = .36. We were unable to perform statistical analysis on the type of transplant (allogeneic vs autologous), and time from ursodiol initiation to transplant. Finally, despite our a priori subgroup analysis, unexplained differences in results (ie, heterogeneity) continued to exist between studies. These differences were only partially explained by analysis based on diagnostic criteria. I2 (the test statistic used to describe heterogeneity) decreased to 0% for the modified Seattle criteria group but remained high (76%) for the Seattle criteria group. This review supports the assertion that ursodiol decreases the incidence of VOD in patients receiving HSCT. However, unexplained heterogeneity weakens our inference (Table1).Table 1Estimate of Risk for Developing VODSubgroupInvestigations Contributing dataOR with 95% Confidence IntervalI2All trialsOhashi, Ruutu, Essell 92, and 98, Carerras, Thompson0.33 [0.12, 0.90]67.6%Clinical trialOhashi, Ruutu, Essell 980.30 [0.03, 2.80]70.5%Observational studyThompson, Carerras, Essell 920.36 [0.11, 1.23]80.4%Busulfan conditioned patientsEssell 92, Essell 98, Ohashi0.19 [0.06, 0.59]41%TBI conditioned patientsOhashi, Ruutu0.37 [0.03, 4.84]67%Seattle criteriaEssell 92, Essell 98, Ruutu, Thompson0.40 [0.12, 1.37]76%modified Seattle criteriaCarerras, Ohashi0.17 [0.04, 0.64]0%Allogeneic transplant recipientsEssell 92, Essell 98, Ohashi, Ruutu, Thompson0.33 [0.11, 0.99]73.7%I2 represents the precentage of unexplained heterogeneity. Open table in a new tab I2 represents the precentage of unexplained heterogeneity.
Authors: A. Zirakzadeh, V. Montori, H. Imran, M. Litzow, S. Kumar
Institution: Mayo Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2099336186