EFFICACY OF HEPATIC TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

Controlled trials to assess the therapeutic benefit of orthotopic hepa tic transplantation (OHTx) for primary sclerosing cholangitis (PSC) ca nnot be justified in view of improvement of patient survival after thi s operation since 1981. However, the actual patient survival with OHTx can be compared with the Mayo model estimated survival probabilities without OHTx. This model, which encompasses physical, biochemical and histopathologic parameters of PSC, was constructed from a study of 392 conservatively treated PSC patients at five international centers in England and North America. We compared the actual survival of 216 adul t patients with die diagnosis of advanced PSC who underwent hepatic re placement with die expected survival estimated by die Mayo PSC natural history model, ''the simulated control technique.'' OHTx was performe d at the University of Pittsburgh and Mayo Medical Center between 5 De cember 1981 and 26 December 1990. The mean (plus or minus standard dev iation) post-OHTx follow-up period was 34+/-25 months (range of zero t o 104 months). Before transplantation, biliary or portal hypertensive operation, or both, was performed upon 104 patients. At operation, the mean age of recipients was 42.1+/-11.3 years and the mean value of to tal serum bilirubin was 13.3+/-13.0 milligrams per deciliter. Extensiv e septal fibrosis and cirrhosis were histologically documented in 97 p ercent of the patients, with splenomegaly in 63 percent. Immunosuppres sive therapy was based primarily on cyclosporin in 184 recipients and FK-506 in 32. Within six months, the Kaplan-Meier survival probability after OHTx (0.89) already was higher than predicted by the Mayo model (0.83). At five years, the Kaplan-Meier actual survival with OHTx was 0.73 compared with 0.28 expected Mayo model survival. The overall inc reased survival rate with transplantation was statistically significan t (chi-square equals 126.6; p<0.001). At all risk stratifications, OHT x significantly improved survival with a p value of 0.031 (low risk), 0.001 (moderate risk) and <0.001 (high risk). Thus, OHTx is effective therapy for PSC. Disease gravity and unsuspected cholangiocarcinoma in the excised native fiver adversely influenced short and long term sur vival rates after transplantation, respectively.