Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2021; 27(27): 4252-4275
Published online Jul 21, 2021. doi: 10.3748/wjg.v27.i27.4252
Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence?
Nikolaos Fragkou, Lazaros Sideras, Panteleimon Panas, Christos Emmanouilides, Emmanouil Sinakos
Nikolaos Fragkou, Lazaros Sideras, Panteleimon Panas, Emmanouil Sinakos, Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
Christos Emmanouilides, Department of Oncology, Interbalkan Medical Center, Thessaloniki 57001, Greece
Author contributions: Fragkou N and Emmanouilides C drafted the article; Sideras L and Panas P contributed to the acquisition and analyses of data; Sinakos E designed the study, made critical revisions related to important intellectual content of the manuscript, and approved the final version of the study.
Conflict-of-interest statement: All authors have no conflict of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Emmanouil Sinakos, MD, PhD, Assistant Professor, Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, Greece. em_sinakos@yahoo.com
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: March 29, 2021
Revised: April 12, 2021
Accepted: June 18, 2021
Article in press: June 18, 2021
Published online: July 21, 2021
Processing time: 172 Days and 7 Hours
Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.

Keywords: Cholangiocarcinoma; Hepatitis B; Intrahepatic; Hepatocellular carcinoma; Resection; Chemotherapy

Core Tip: Cholangiocarcinoma (CCA) is the second most common primary liver cancer. Intrahepatic CCA (iCCA), a subgroup of CCA, has a pronounced association with hepatitis B virus (HBV) infection. Recent data have strengthened this association both in terms of epidemiology and pathogenesis. Moreover, the potential for the development of the combined hepatocellular-cholangiocarcinoma form poses additional difficulties in the successful management of iCCA. Herein, we discuss the available epidemiological data, present the current knowledge on the pathogenesis of HBV-associated iCCA, and review all of the available information on the diagnosis and management of this aggressive cancer.