Clinical Research Papers:

Subclinical involvement of the liver is associated with prognosis in treatment naïve cancer patients

Noemi Pavo, Markus Raderer, Georg Goliasch, Raphael Wurm, Guido Strunk, Anna Cho, Johannes F. Novak, Heinz Gisslinger, Günther G. Steger, Michael Hejna, Wolfgang Köstler, Sabine Zöchbauer-Müller, Christine Marosi, Gabriela Kornek, Leo Auerbach, Sven Thorben Schneider, Bernhard Parschalk, Werner Scheithauer, Robert Pirker, Barbara Kiesewetter, Richard Pacher, Christoph Zielinski and Martin Hülsmann _

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Oncotarget. 2017; 8:81250-81260. https://doi.org/10.18632/oncotarget.17131

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Noemi Pavo1, Markus Raderer2, Georg Goliasch1, Raphael Wurm1, Guido Strunk3, Anna Cho1, Johannes F. Novak1, Heinz Gisslinger2, Günther G. Steger2, Michael Hejna2, Wolfgang Köstler2, Sabine Zöchbauer-Müller2, Christine Marosi2, Gabriela Kornek2, Leo Auerbach4, Sven Thorben Schneider5, Bernhard Parschalk5, Werner Scheithauer2, Robert Pirker2, Barbara Kiesewetter2, Richard Pacher1, Christoph Zielinski2 and Martin Hülsmann1

1 Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

2 Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria

3 Complexity Research, Vienna, Austria

4 Department of Gynaecology, Medical University of Vienna, Vienna, Austria

5 Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Vienna, Austria

Correspondence to:

Martin Hülsmann, email:

Keywords: cancer, liver, biomarker, inflammation, prognosis

Received: December 29, 2016 Accepted:April 04, 2017 Published: April 16, 2017


Background. Routinely tested liver biomarkers as alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), butyryl-cholinesterase (BChE), albumin and bilirubin are altered in distinct malignancies and hepatic metastases. This study aimed to investigate whether all liver parameters have the ability to predict long-term mortality in treatment naïve cancer patients but without a malignant hepatic involvement.

Methods. We prospectively enrolled 555 consecutive patients with primary diagnosis of cancer without prior anticancer therapy. BChE, albumin, AST, ALT, GGT and bilirubin as well as the inflammatory makers C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were determined. All-cause mortality was defined as primary endpoint.

Results. During a median follow-up of 25 (IQR16-31) months 186 (34%) patients died. All liver parameters were significantly associated with all-cause mortality (p < 0.001 for all). However, for patients without a malignant primary or secondary hepatic involvement (82%) only the functional parameters BChE and albumin remained significantly associated with the primary endpoint (crude HR per 1-IQR increase 0.61, 95%CI:0.49-0.77; p < 0.001 for BChE and 0.58, 95%CI:0.47-0.70; p < 0.001 for albumin). This e ect was persistent after multivariate adjustment (adj.HR per 1-IQR increase 0.65, 95%CI:0.50-0.86; p = 0.002 for BChE and 0.63, 95%CI:0.50-0.79; p < 0.001 for albumin). BChE and albumin correlated inversely with CRP (r = -0.21, p < 0.001 and r = -0.36, p < 0.001), SAA (r = -0.19, p < 0.001 and r = -0.33, p < 0.001) and IL-6 (r = -0.13, p = 0.009 and r = -0.17, p = 0.001).

Conclusions. Decreased serum BChE and albumin levels are associated with increased all-cause mortality in treatment-naïve cancer patients without a manifest malignant hepatic involvement irrespective of tumor entity or stage. This association may reflect progressing systemic inflammation and metabolic derangement with subclinical involvement of the liver.

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