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Digestive Diseases and Sciences

, Volume 60, Issue 12, pp 3642–3646 | Cite as

Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis

  • Howard C. Masuoka
  • Raj Vuppalanchi
  • Ross Deppe
  • Phelan Bybee
  • Megan Comerford
  • Suthat Liangpunsakul
  • Marwan Ghabril
  • Naga Chalasani
Original Article

Abstract

Background and Aim

Hepatocyte apoptosis or necrosis from accumulation of bile salts may play an important role in the disease progression of primary sclerosing cholangitis (PSC). The aim of the current study was to measure serum markers of hepatocyte apoptosis (cytokeratin-18 fragments—K18) and necrosis (high-mobility group protein B1—HMGB1) in adults with PSC and examine the relationship with disease severity.

Methods

We measured serum levels of K18 and HMGB1 in well-phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was assessed biochemically, histologically, and PSC Mayo risk score. Quantification of hepatocyte apoptosis was performed using TUNEL assay.

Results

The mean age of the study cohort was 49.7 ± 13.3 years and comprised of 67 % men and 93 % Caucasian. Serum K18 levels were significantly higher in the PSC patients compared to control (217.4 ± 78.1 vs. 157.0 ± 58.2 U/L, p = 0.001). However, HMGB1 levels were not different between the two groups (5.38 ± 2.99 vs. 6.28 ± 2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total bilirubin (r = 0.61, p ≤ 0.001), and albumin (r = −0.4, p = 0.02). Serum K18 levels also correlated with the level of apoptosis present on the liver biopsy (r = 0.8, p ≤ 0.001) and Mayo risk score (r = 0.4, p = 0.015).

Conclusion

Serum K18 but not HMGB1 levels were increased in PSC and associated with severity of underlying liver disease and the degree of hepatocyte apoptosis.

Keywords

Serum K18 TUNEL HMGB1 Apoptosis Hepatocyte necrosis Ulcerative colitis 

Abbreviations

ALT

Alanine aminotransferase

Alk P

Alkaline phosphatase

AST

Aspartate aminotransferase

HMGB1

High-mobility group protein B1

K18

Cytokeratin-18 fragment

PSC

Primary sclerosing cholangitis

TUNEL

Terminal deoxynucleotidyl transferase dUTP nick end labeling

Notes

Acknowledgments

This work was in part supported by NIH K24 DK069290A (NC).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Howard C. Masuoka
    • 1
  • Raj Vuppalanchi
    • 1
  • Ross Deppe
    • 1
    • 2
  • Phelan Bybee
    • 1
    • 2
  • Megan Comerford
    • 1
  • Suthat Liangpunsakul
    • 1
  • Marwan Ghabril
    • 1
  • Naga Chalasani
    • 1
    • 2
    • 3
  1. 1.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Cellular and Integrative PhysiologyIndiana University School of MedicineIndianapolisUSA
  3. 3.David W. Crabb Professor of MedicineIndianapolisUSA

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