Ursodiol to prevent hepatic venoocclusive disease

VOD is an important cause of morbidity and mortality in patients following allogeneic bone marrow transplantation. Although VOD may improve in some patients, severe cases are often fatal. There is no established therapy to prevent progression to severe VOD; nor are there any conclusive or universally accepted methods for prevention of mortality associated with severe VOD. A treatment that could minimize hepatic damage and cause VOD to manifest as reversible liver damage rather than a progressive, fatal disease would indeed have a place in posttransplant therapy. Nontoxic ursodiol may play such a role by replacing hepatotoxic bile acids. Based on the limited available literature (2 studies), it is difficult to draw firm conclusions regarding the use of ursodiol to prevent VOD, although the preliminary results are promising. The studies, although small and not without weakness, suggested that ursodiol effectively reduces the incidence of VOD in allogeneic BMT patients. They do not, however, suggest that ursodiol is effective as treatment for existing VOD, as this was not studied. Also, conclusions were based on patients given busulfan and cyclophosphamide as conditioning therapy and thus might not apply to patients conditioned by other means such as total body irradiation. In summary, the available data do not definitively support the use of ursodiol; however, patients conditioned with busulfan and cyclophosphamide who are at risk for VOD (e.g., pretransplant liver disease, liver metastases) may be candidates for ursodiol prophylactic therapy. Larger, randomized clinical trials are warranted to further define the potential role of ursodiol for the prevention of venoocclusive disease of the liver in BMT patients.