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; Martin Hülsmann

doi:10.18632/oncotarget.17131

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

Oncotarget. 2017 Apr 16;8(46):81250-81260. doi: 10.18632/oncotarget.17131. eCollection 2017 Oct 6.

Authors

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, Martin Hülsmann¹

Affiliations

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.

Abstract

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.

Keywords: biomarker; cancer; inflammation; liver; prognosis.