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.

Original languageEnglish (US)
Pages (from-to)3642-3646
Number of pages5
JournalDigestive Diseases and Sciences
Volume60
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Sclerosing Cholangitis
Necrosis
Biomarkers
Apoptosis
HMGB1 Protein
Hepatocytes
Serum
High Mobility Group Proteins
Keratin-18
In Situ Nick-End Labeling
Bile Acids and Salts
Bilirubin
Alkaline Phosphatase
Disease Progression
Liver Diseases
Albumins
Cohort Studies
K-18 conjugate
Biopsy
Liver

Keywords

  • Apoptosis
  • Hepatocyte necrosis
  • HMGB1
  • Serum K18
  • TUNEL
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

@article{3451e43f46ea42e39872b0a813626549,
title = "Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis",
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 = "Apoptosis, Hepatocyte necrosis, HMGB1, Serum K18, TUNEL, Ulcerative colitis",
author = "Howard Masuoka and Raj Vuppalanchi and Ross Deppe and Phelan Bybee and Megan Comerford and Suthat Liangpunsakul and Marwan Ghabril and Naga Chalasani",
year = "2015",
month = "12",
day = "1",
doi = "10.1007/s10620-015-3805-7",
language = "English (US)",
volume = "60",
pages = "3642--3646",
journal = "Digestive Diseases and Sciences",
issn = "0163-2116",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis

AU - Masuoka, Howard

AU - Vuppalanchi, Raj

AU - Deppe, Ross

AU - Bybee, Phelan

AU - Comerford, Megan

AU - Liangpunsakul, Suthat

AU - Ghabril, Marwan

AU - Chalasani, Naga

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Hepatocyte necrosis

KW - HMGB1

KW - Serum K18

KW - TUNEL

KW - Ulcerative colitis

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U2 - 10.1007/s10620-015-3805-7

DO - 10.1007/s10620-015-3805-7

M3 - Article

C2 - 26195313

AN - SCOPUS:84946490352

VL - 60

SP - 3642

EP - 3646

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

SN - 0163-2116

IS - 12

ER -