Published online Sep 27, 2023. doi: 10.4254/wjh.v15.i9.1013
Peer-review started: April 7, 2023
First decision: June 25, 2023
Revised: July 17, 2023
Accepted: August 23, 2023
Article in press: August 23, 2023
Published online: September 27, 2023
Surrogate endpoints are needed to estimate clinical outcomes in primary sclerosing cholangitis (PSC). Serum alkaline phosphatase was among the first markers studied, but there is substantial variability in alkaline phosphatase levels during the natural history of PSC without intervention. The Mayo risk score incorporates noninvasive variables and has served as a surrogate endpoint for survival for more than two decades. Newer models have better test performance than the Mayo risk score, including the primary sclerosing risk estimate tool (PREsTo) model and UK-PSC score that estimate hepatic decompensation and transplant free survival, respectively. The c-statistics for transplant-free survival for the Mayo risk model and the long-term UK-PSC model are 0.68 and 0.85, respectively. The c-statistics for hepatic decompensation for the Mayo risk model and PREsTo model are 0.85 and 0.90, respectively. The Amsterdam-Oxford model included patients with large duct and small duct PSC and patients with PSC-autoimmune hepatitis overlap and had a c-statistic of 0.68 for transplant-free survival. Other noninvasive tests that warrant further validation include magnetic resonance imaging, elastography and the enhanced liver fibrosis score. Prognostic models, noninvasive tests or a combination of these surrogate endpoints may not only serve to be useful in clinical trials of investigational agents, but also serve to inform our patients about their prognosis.
Core Tip: Several noninvasive prognostic models have been validated that improve upon serum alkaline phosphatase and the Mayo risk score or include subgroups of patients not validated by these tests. The UK-PSC score has superior test performance compared to the Mayo risk score for short and long term transplant free survival. The Primary sclerosing risk estimate tool (PREsTo) has excellent test performance for risk of hepatic decompensation. The Amsterdam-Oxford model includes patients with small duct primary sclerosing cholangitis (PSC) and PSC-autoimmune hepatitis overlap. Elastography and magnetic resonance imaging show promise as prognostic tools.