Efficacy of hepatic transplantation in patients with primary sclerosing cholangitis

Abstract

Controlled trials to assess the therapeutic benefit of orthotopic hepatic transplantation (OHTx) for primary sclerosing cholangitis (PSC) cannot be justified in view of improvement of patient survival after this 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 adult patients with the diagnosis of advanced PSC who underwent hepatic replacement with the expected survival estimated by the Mayo PSC natural history model, "the simulated control technique." OHTx was performed at the University of Pittsburgh and Mayo Medical Center between 5 December 1981 and 26 December 1990. The mean (plus or minus standard deviation) post-OHTx follow-up period was 34 +/- 25 months (range of zero to 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 total serum bilirubin was 13.3 +/- 13.0 milligrams per deciliter. Extensive septal fibrosis and cirrhosis were histologically documented in 97 percent of the patients, with splenomegaly in 63 percent. Immunosuppressive 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 increased survival rate with transplantation was statistically significant (chi-square equals 126.6; p < 0.001). At all risk stratifications, OHTx 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 liver adversely influenced short and long term survival rates after transplantation, respectively.

Fig. 1

Actual (Kaplan-Meier) survival after transplantation in 216 patients with primary sclerosing cholangitis and their estimated survival without transplantation as predicted by the Mayo model “simulated control.”

Fig. 2

Actual (Kaplan-Meier) survival after transplantation in three risk groups of patients with primary sclerosing cholangitis and the estimated survival without transplantation as predicted by the Mayo natural history model. These risk groups were formed on the basis of pretransplantation Mayo-model risk scores with a cutoff value of 4.8 for the low risk and 5.4 for the moderate risk group.

Fig. 3

Kaplan-Meier actual survival after transplantation in patients with primary sclerosing cholangitis with and without inflammatory intestinal disease. The actual survival rate at five year is 0.70±0.09 and 0.88±0.05 for each subgroup, respectively.

Fig. 4

Actual (Kaplan-Meier) survival after transplantation in patients with primary sclerosing cholangitis with and without a history of biliary and portal hypertensive operation before transplantation. The actual survival rate at five year is 0.67±0.06 and 0.78±0.05 for each subgroup, respectively.

Fig. 5

Kaplan-Meier survival plot after transplantation in patients with primary sclerosing cholangitis with and without detection of cholangiocarcinoma in the excised liver. The difference was statistically significant, with a five-year survival rate of 0.47±0.17 and 0.75±0.04, respectively.

Fig. 6

Actual (Kaplan-Meier) survival after transplantation in patients with primary sclerosing cholangitis who had incidental cholangiocarcinoma and the estimated (Mayo Model) survival rate without transplantation. The three year survival rate is 0.47±0.17 and 0.31, respectively.

Fig. 7

Actual (Kaplan-Meier) survival after transplantation in patients with primary sclerosing cholangitis subclassified according to the used immunosuppressive regimen.

Fig. 8

Scatter plots for the Mayo model risk score values of the patients with primary sclerosing cholangitis who received transplantation each year among the three immunosuppressive groups.