Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation

Abstract

Primary sclerosing cholangitis (PSC) is the fourth leading diagnosis in liver transplant recipients in the UnitedStates. The disease is known to recur in 15% to 30% of liver transplant recipients. We set out to investigate how different immunosuppression regimens affected natural history of PSC after liver transplantation at our center. We reviewed records of all patients who underwent a liver transplantation at our institution in between 1988 and 2000 and had a diagnosis of PSC at the time of liver transplantation. Primary sclerosing cholangitis recurred in 15 of 71 patients (21.1%) who had complete records and survived more than 30 days after liver transplantation. Although recurrence of primary sclerosing cholangitis was most often seen (but not statistically significantly so) in patients who received maintenance corticosteroids, the time to recurrence was not significantly different between those who were treated with maintenance, those who were not successfully weaned, and those who successfully weaned off corticosteroids within 3 months after liver transplantation. Orthoclone (OKT3) therapy (Ortho-Biotech, Inc., Raritan, NJ) was associated with a higher risk of primary sclerosing cholangitis recurrence (29% versus 10%, P < .05). Recurrence was not influenced by immunosuppression with either cyclosporine or tacrolimus. Coexistent inflammatory bowel disease was a cause of failure to wean off corticosteroids, was associated with a shorter time to recurrence of sclerosing cholangitis, and was responsible for significant comorbidity (colon cancer in 7.3%). Primary sclerosing cholangitis recurrence is commonly seen after liver transplantation. More immunosuppression seems to be detrimental to the outcome of our patients with sclerosing cholangitis: use of OKT3 was associated with a greater incidence of recurrence. Length of corticosteroid use did not affect timing or risk of recurrence, and because it has been proven that early corticosteroid withdrawal after liver transplantation is beneficial, we continue to recommend this practice. (Liver Transpl 2003;9:727-732.)

Primary sclerosing cholangitis: Summary of a workshop

“…[158][159][160][161] The reported frequency of recurrent PSC ranged from 1% to 33%, the variation related in part to differences in diagnostic criteria, duration of follow up, and rigor with which the diagnosis is sought. 150,[162][163][164][165][166] Factors associated with recurrence were steroid-resistant rejection, OKT3 use, preservation injury, ABO incompatibility, cytomegalovirus infection, lack of history of colectomy, male sex, and donor-recipient gender mismatch, but not specific calcineurin inhibitor use or frequency of rejection. [162][163][164][165][166][167] A critical issue is whether recurrence of PSC adversely affects outcome.…”

“…150,[162][163][164][165][166] Factors associated with recurrence were steroid-resistant rejection, OKT3 use, preservation injury, ABO incompatibility, cytomegalovirus infection, lack of history of colectomy, male sex, and donor-recipient gender mismatch, but not specific calcineurin inhibitor use or frequency of rejection. [162][163][164][165][166][167] A critical issue is whether recurrence of PSC adversely affects outcome. Instances of graft failure due to recurrent PSC are rare and often confounded by the presence of other forms of liver injury.…”

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis ‐ a pilot study

“…1,2 Liver transplantation (LT) is the only existing treatment shown to prolong survival; however, PSC recurs in up to one-third of deceased donor LT and up to two-thirds of living-related donor LT patients. 3,4 The most widely studied pharmacological agent in the treatment of cholestatic liver diseases, ursodeoxycholic acid (UDCA), improves serum liver tests in PSC, but unlike in primary biliary cirrhosis, does not appear to delay disease progression. [5][6][7] Furthermore, a recent large randomised trial has found highdose UDCA to be associated with serious adverse effects (AEs) in patients with PSC.…”

Survival Without Biliary Complications After Liver Transplant for Primary Sclerosing Cholangitis

“…Steroid-resistant rejection, 5,33 and treatment with muromonab-CD3 are risk factors for the recurrence of primary sclerosing cholangitis after orthotopic liver transplant. In the present patients, we found no effect of acute cellular rejection on recurrent primary sclerosing cholangitis, and the number of steroidresistant episodes of rejection that necessitated antibody treatment was not different between the groups (Table 3).…”