O’Rourke JM, Sagar VM, Shah T, Shetty S. Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer. World J Gastroenterol 2018; 24(39): 4436-4447 [PMID: 30357021 DOI: 10.3748/wjg.v24.i39.4436]
Corresponding Author of This Article
Shishir Shetty, MBChB, MRCP, PhD, Senior Research Fellow, Centre for Liver Research, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom. s.shetty@bham.ac.uk
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Oct 21, 2018; 24(39): 4436-4447 Published online Oct 21, 2018. doi: 10.3748/wjg.v24.i39.4436
Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer
Joanne Marie O’Rourke, Vandana Mridhu Sagar, Tahir Shah, Shishir Shetty
Joanne Marie O’Rourke, Vandana Mridhu Sagar, Shishir Shetty, Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
Joanne Marie O’Rourke, Vandana Mridhu Sagar, Tahir Shah, Shishir Shetty, NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, United Kingdom
Author contributions: Shetty S contributed to review concept, literature review and writing the paper; O’Rourke JM contributed to the literature review and writing the paper; Sagar VM and Shah T provided critical intellectual revisions and editing of the manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Shishir Shetty, MBChB, MRCP, PhD, Senior Research Fellow, Centre for Liver Research, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom. s.shetty@bham.ac.uk
Telephone: +44-121-3714852
Received: May 9, 2018 Peer-review started: May 9, 2018 First decision: June 15, 2018 Revised: September 3, 2018 Accepted: October 5, 2018 Article in press: October 5, 2018 Published online: October 21, 2018
Abstract
Hepatocellular carcinoma (HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.
Core tip: In this review, we discuss the development of hepatocellular carcinoma in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumorigenic climate and the implications this has for patient management.
