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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2016; 8(12): 533-544
Published online Apr 28, 2016. doi: 10.4254/wjh.v8.i12.533
Incidence, risk factors and outcomes of de novo malignancies post liver transplantation
Pavan Kedar Mukthinuthalapati, Raghavender Gotur, Marwan Ghabril
Pavan Kedar Mukthinuthalapati, Raghavender Gotur, Marwan Ghabril, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Author contributions: Mukthinuthalapati PK interpretation of literature, drafting and final approval of the article; Gotur R interpretation of literature, drafting and final approval of the article; Ghabril M interpretation of literature, drafting and final approval of the article.
Conflict-of-interest statement: All the authors have no conflicts to report.
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:
Correspondence to: Marwan Ghabril, MD, Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle 225, Indianapolis, IN 46202, United States.
Telephone: +1-317-2781630 Fax: +1-317-2786870
Received: January 9, 2016
Peer-review started: January 10, 2016
First decision: February 22, 2016
Revised: March 8, 2016
Accepted: April 5, 2016
Article in press: April 6, 2016
Published online: April 28, 2016

Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression.

Keywords: Liver transplant, Immunosuppression, Risk, Outcomes, Malignancy

Core tip: The risk of new cancers is significantly increased after liver transplantation (LT), and is driven by patient factors, oncogenic viruses and lifelong immunosuppression. De novo malignancy is a major risk factor for mortality after LT, equaling the risk of cardiovascular disease or infectious diseases. The risk of de novo malignancies may be reduced by attention to patient risk factors and minimization of immunosuppression when possible. Ultimately rigorous surveillance is needed to allow for early diagnosis and attenuation of mortality risk.