Research Papers:

Effect of liver fibrosis on survival in patients with intrahepatic cholangiocarcinoma: a SEER population-based study

Nimrod Adatto Levy, Guy Kern, Daniel Shepshelovich, Oren Shibolet, Rami Hershkoviz and Ofer Isakov _

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Oncotarget. 2020; 11:4438-4447. https://doi.org/10.18632/oncotarget.27820

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Nimrod Adatto Levy1, Guy Kern1, Daniel Shepshelovich1, Oren Shibolet2,3, Rami Hershkoviz1 and Ofer Isakov1

1 Internal Medicine “T”, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

2 Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

3 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence to:

Ofer Isakov,email: [email protected]

Keywords: liver fibrosis; cholangiocarcinoma; SEER; survival; cirrhosis

Received: July 30, 2020     Accepted: November 03, 2020     Published: November 24, 2020

Copyright: © 2020 Levy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Intrahepatic cholangiocarcinoma (iCCA) is a biliary tract malignancy with rising incidence in recent decades. While the causative role of cirrhosis in the development of iCCA is well established, the role of cirrhosis as a prognostic factor in iCCA is debatable.

Materials and Methods: The study population consisted of 512 patients diagnosed with iCCA between 2004–2016 collected from the Surveillance, Epidemiology and End Results (SEER) database. The impact of fibrosis on overall and cancer-specific survival 12, 36 and 60 months following diagnosis, was evaluated in the entire cohort and in sub-groups stratified according to treatment approach and the American Joint Committee on Cancer (AJCC) tumor stage using a Cox proportional-hazards model.

Results: After adjusting for age, sex, race, year of diagnosis, AJCC stage, and surgical treatment strategy, advanced fibrosis was associated with worse cancer-specific survival across follow up periods (HR 1.49 (1.13–1.96, p = 0.005); HR 1.44 (1.14–1.83, p = 0.002) and HR 1.45 (1.15–1.83, p = 0.002) for 12, 36 and 60 months, respectively). Similar effects were observed for overall survival. Among patients that underwent surgical resection, advanced fibrosis was associated with worse overall survival and cancer-specific survival across follow up periods. Fibrosis was associated with worse overall and cancer-specific survival in patients with a later stage (III–IV) at diagnosis but this effect was not demonstrated in early stages.

Conclusions: Patients with iCCA and advanced liver fibrosis have an increased risk of both overall and cancer-specific mortality compared to patients with earlier stages of fibrosis.

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