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

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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.

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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

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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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Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Howard C. Masuoka, Raj Vuppalanchi, Ross Deppe, Phelan Bybee, Megan Comerford, Suthat Liangpunsakul, Marwan Ghabril & Naga Chalasani

  2. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Ross Deppe, Phelan Bybee & Naga Chalasani

  3. David W. Crabb Professor of Medicine, 702 Rotary Building, Suite 225, Indianapolis, IN, 46202, USA

    Naga Chalasani

Authors
  1. Howard C. Masuoka
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  2. Raj Vuppalanchi
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  3. Ross Deppe
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  5. Megan Comerford
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  6. Suthat Liangpunsakul
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  7. Marwan Ghabril
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  8. Naga Chalasani
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Correspondence to Naga Chalasani.

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Masuoka, H.C., Vuppalanchi, R., Deppe, R. et al. Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis. Dig Dis Sci 60, 3642–3646 (2015). https://doi.org/10.1007/s10620-015-3805-7

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  • DOI: https://doi.org/10.1007/s10620-015-3805-7

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