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. 2019 Oct;8(13):5916-5929.
doi: 10.1002/cam4.2373. Epub 2019 Aug 20.

Inflammatory Markers in Intrahepatic Cholangiocarcinoma: Effects of Advanced Liver Disease

Free PMC article

Inflammatory Markers in Intrahepatic Cholangiocarcinoma: Effects of Advanced Liver Disease

Cortlandt M Sellers et al. Cancer Med. .
Free PMC article


Background: To investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status.

Methods: In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan-Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA).

Results: About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child-Pugh A patients (P < 0.01). In Child-Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child-Pugh class A (n = 94), low-NLR had higher OS vs high-NLR (25.4 vs 12.2 months, P < 0.01). In Child-Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low- vs high-NLR: 6.7 vs 2.9 months, P = 0.2). Child-Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124).

Conclusions: The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.

Keywords: bile ducts; cholangiocarcinoma; intrahepatic; liver cirrhosis; lymphocytes; neutrophils; platelets.

Conflict of interest statement

The authors have no conflicts of interest to report. The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. Hyun S. Kim served on Advisory boards for Boston Scientific and SIRTex.


Figure 1
Figure 1
Overall survival by treatment group. A, Entire cohort; B, Child‐Pugh A patients; C, Child‐Pugh B patients
Figure 2
Figure 2
Overall survival by inflammatory marker groups. A, Neutrophil‐to‐lymphocyte ratio. B, Platelet‐to‐lymphocyte ratio. C, Systemic immune‐inflammation index
Figure 3
Figure 3
Overall survival by neutrophil‐to‐lymphocyte ratio and Child‐Pugh status. A, Child‐Pugh A patients. B, Child‐Pugh B patients

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