Z Gastroenterol 2019; 57(01): e33
DOI: 10.1055/s-0038-1677127
2. Clinical Hepatology, Surgery, LTX
Georg Thieme Verlag KG Stuttgart · New York

Serum CYFRA 21 – 1 levels are elevated in advanced liver disease and associate with poor survival

K Hamesch
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
N Guldiken
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
M Aly
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
2   Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt
,
N Hueser
3   Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Surgery, Munich, Germany
,
D Hartmann
3   Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Surgery, Munich, Germany
,
C Trautwein
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
S Mueller
4   Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany;
,
P Nahon
5   AP-HP, Service d'Hépatologie, Hopital Jean Verdier, Bondy, France;
6   Université Paris 13, Sorbonne Paris Cité, “Equipe labellisée Ligue Contre le Cancer”, F-93206 Saint-Denis, France;
7   Inserm, UMR-1162, “Génomique fonctionnelle des tumeur solides”, F-75000 Paris, France;
,
M Ziol
8   Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France;
9   Université Paris Diderot, IUH, F-75010 Paris;
10   Pathology Department, GH Paris-Seine-Saint-Denis, APHP, Bondy;
,
T Bruns
11   Department of Internal Medicine IV, Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Jena, Germany
12   Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
,
P Strnad
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

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Background:

Keratins (Ks) constitute a large family of tissue-specifically expressed proteins. Among them, K18 is abundantly expressed in hepatocytes while K19 is found in ductular cells of the liver and represents the most widely used ductular reaction (DR) marker. While the K18-based serum fragments M30/M65 are commonly used liver disease predictors, K19 fragments as detected via CYFRA 21 – 1 are established tumor markers but their usefulness in liver disease remains unknown. Therefore, we systematically evaluated hepatic K19 expression and serum CYFRA 21 – 1 levels in liver disease.

Methods:

Hepatic mRNA expression of DR markers was analyzed in 63 patients with chronic liver disease. Serum CYFRA 21 – 1 levels were measured in the following cohorts: (i) 52 alcohol misusers prior and after detoxification therapy, (ii) 280 German patients with decompensated cirrhosis, (iii) 231 French patients with alcoholic cirrhosis.

Results:

Hepatic K19 mRNA expression was comparable in F0-F3 fibrosis stages, but significantly increased in cirrhotics as confirmed by immunoblotting. K19 mRNA correlated strongly with levels of other DR-expressed keratins, i.e. K7/K23. In active alcohol misusers, CYFRA 21 – 1 levels were increased in patients with higher liver stiffness (i.e. LSM ≥15 kPa; a surrogate of advanced liver disease) compared to patients with LSM < 15 kPa (3.71 (2.20 – 4.53) vs. 1.42 (0.23 – 2.33) ng/mL, p =.002). Comparable CYFRA 21 – 1 levels were seen before and after a detoxification therapy (median duration 7 days). The strong correlation between both values (r =.744, p<.0001) indicated that CYFRA 21 – 1 constitutes a rather stable parameter. In German patients with decompensated cirrhosis, serum CYFRA 21 – 1 predicted 90-day transplant-free survival (HR = 2.97 [1.92 – 4.60], p<.0001) and its diagnostic accuracy was similar to the MELD and ACLF scores (AUROC 0.64, 0.70 and 0.68, respectively). CYFRA 21 – 1's usefulness was confirmed in French patients with alcoholic cirrhosis, where elevated serum CYFRA 21 – 1 prognosticated liver-related death (HR = 2.59 [1.64 – 4.09], p<.001) and HCC occurrence (HR = 1.74 [1.02 – 296], p =.039).

Conclusion:

Hepatic K19 and serum CYFRA 21 – 1 levels rise in cirrhotics and in the latter, increased CYFRA 21 – 1 levels associate with a poor prognosis. Hence, the DR-related CYFRA 21 – 1 constitutes an attractive prognostic marker in advanced liver disease.