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An update on primary sclerosing cholangitis epidemiology, outcomes and quantification of alkaline phosphatase variability in a population-based cohort

  • Zeinab Bakhshi
  • Moira B. Hilscher
  • Gregory J. Gores
  • William S. Harmsen
  • Jason K. Viehman
  • Nicholas F. LaRusso
  • Andrea A. Gossard
  • Konstantinos N. Lazaridis
  • Keith D. Lindor
  • John E. EatonEmail author
Original Article—Alimentary Tract
  • 71 Downloads

Abstract

Background

Contemporary primary sclerosing cholangitis (PSC) population-based cohorts describing the epidemiology, natural history, and long-term fluctuations in serum alkaline phosphatase (SAP) and their prognostic relevance are lacking. Therefore, we investigated the incidence and natural history of PSC and quantified SAP fluctuations among those with PSC in Olmsted County, Minnesota over the last 41 years.

Methods

The Rochester Epidemiology Project was used to identify 56 subjects diagnosed with PSC between 1976 and 2017 in Olmsted County. The primary endpoint (n = 19) included liver transplantation, hepatic decompensation, and cholangiocarcinoma.

Results

The age- and sex-adjusted incidence of PSC (per 100,000 person years) nearly doubled from 2001 to 2017 compared to 1976–2000 (1.47; 95% CI 0.99–1.96 versus 0.79; 95% CI 0.42–1.16, p = 0.02). This increase paralleled a rise in patients with markers of a milder phenotype at the time of diagnosis: normal SAP (26.32% versus 0%, p < 0.01) and lower Mayo PSC risk score [0.36 (− 0.57 to 1.55) versus − 0.50 (− 1.25 to 0.35), p = 0.03]. Intra-individual SAP fluctuates with a median coefficient of variation of 36.20%. SAP normalization and dropping below 1.5 × upper limit of normal (ULN) occurs at a rate of 5% and 10% per year, respectively. SAP less than 1.5 × ULN was associated with a lower risk of PSC-related complications (hazard ratio 0.11; 95% CI 0.03–0.42).

Conclusions

The patients with PSC are increasingly being diagnosed with a milder phenotype. While a lower SAP is associated with improved outcomes, the high intra-individual variation of SAP levels calls into question the practice of using a single SAP value as a surrogate endpoint in clinical trials.

Keywords

Primary sclerosing cholangitis Cirrhosis Liver function tests Epidemiology Cholangiocarcinoma 

Abbreviations

PSC

Primary sclerosing cholangitis

IBD

Inflammatory bowel disease

SAP

Serum alkaline phosphatase

ULN

Upper limit of normal

REP

Rochester epidemiologic project

CCA

Cholangiocarcinoma

HD

Hepatic decompensation

MELD

Model for end-stage liver disease

PREsTo

PSC risk estimate tool

MRCP

Magnetic resonance cholangiopancreatography

CI

Confidence interval

IQR

Interquartile range

LT

Liver transplant

HR

Hazard ratio

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2020_1663_MOESM1_ESM.pdf (320 kb)
Survival of those with PSC versus expected survival among age and gender adjusted Olmsted County residents. (PDF 319 kb)
535_2020_1663_MOESM2_ESM.docx (13 kb)
Supplementary file2 (DOCX 12 kb)

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Copyright information

© Japanese Society of Gastroenterology 2020

Authors and Affiliations

  • Zeinab Bakhshi
    • 1
  • Moira B. Hilscher
    • 1
  • Gregory J. Gores
    • 1
  • William S. Harmsen
    • 2
  • Jason K. Viehman
    • 2
  • Nicholas F. LaRusso
    • 1
  • Andrea A. Gossard
    • 1
  • Konstantinos N. Lazaridis
    • 1
  • Keith D. Lindor
    • 3
  • John E. Eaton
    • 1
    Email author
  1. 1.Division of Gastroenterology and HepatologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  3. 3.Department of Gastroenterology and HepatologyArizona State University College of Health SolutionsPhoenixUSA

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