Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2019; 11(1): 1-18
Published online Jan 27, 2019. doi: 10.4254/wjh.v11.i1.1
Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review
Aakash Desai, Sonia Sandhu, Jin-Ping Lai, Dalbir Singh Sandhu
Aakash Desai, Department of Internal Medicine, Case Western Reserve University/MetroHealth Medical Center, Cleveland, OH 44109, United States
Sonia Sandhu, Department of Hematology and Oncology, Cleveland Clinic/Akron General Medical Center, Akron, OH 44307, United States
Jin-Ping Lai, Department of Pathology, University of Florida, Gainsville, FL 32611, United States
Dalbir Singh Sandhu, Division of Gastroenterology and Hepatology, Case Western Reserve University/MetroHealth Medical Center, Cleveland, OH 44109, the United States
Author contributions: Desai A, Sandhu S, Lai JP and Sandhu DS contributed to the conception and design of the study; Desai A and Sandhu DS contributed to literature review and analysis; Desai A and Sandhu S, Sandhu DS contributed to the drafting of manuscript; Sandhu S and Lai JP contributed to critical revision and editing; all authors equally contributed to approval of the final version.
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:
Corresponding author: Dalbir Singh Sandhu, MD, Assistant Professor, Division of Gastroenterology and Hepatology, Case Western Reserve University/MetroHealth Medical Center, 2500 Metrohealth Drive, Cleveland, OH 44109, United States.
Telephone: +1-216-7785736 Fax: +1-216-7782074
Received: August 24, 2018
Peer-review started: August 24, 2018
First decision: October 4, 2018
Revised: October 4, 2018
Accepted: December 22, 2018
Article in press: December 31, 2018
Published online: January 27, 2019

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide. Despite being the 6th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however, about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features, diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.

Keywords: Hepatocellular carcinoma, Non-cirrhotic liver, Hepatitis B, Hepatitis C, Risk factors, Clinical features, Diagnostic modalities, Management strategies, Future directions

Core tip: Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer related deaths. Majority of HCC arise in a cirrhotic liver, however, 20% of cases can develop in non-cirrhotic liver. This comprehensive review focuses on risk factors, clinical features, diagnostic modalities, management strategies and future directions for HCC in non-cirrhotic liver.