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Song et al. Hepatoma Res 2020;6:27 Hepatoma Research
DOI: 10.20517/2394-5079.2020.05

Review Open Access

Mechanisms and immunotherapies of HBV- and
NAFLD-related hepatocellular carcinoma

Xiao-Jia Song, Chun-Hong Ma

Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical
Science, Shandong University, Jinan 250012, Shandong, China.
Correspondence to: Prof. Chun-Hong Ma, Key Laboratory for Experimental Teratology of Ministry of Education and Department
of Immunology, School of Basic Medical Science, Shandong University, No. 44 Wenhua Xi Road, Jinan 250012, Shandong, China.
E-mail: machunhong@sdu.edu.cn

How to cite this article: Song XJ, Ma CH. Mechanisms and immunotherapies of HBV- and NAFLD-related hepatocellular
carcinoma. Hepatoma Res 2020;6:27. http://dx.doi.org/10.20517/2394-5079.2020.05
Received: 20 Jan 2020 First Decision: 1 Apr 2020 Revised: 3 Apr 2020 Accepted: 10 Apr 2020 Published: 16 May 2020

Science Editors: Jia Fan, Ying-Hong Shi Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Hepatitis B virus (HBV) infection remains the most important risk factor for hepatocellular carcinoma (HCC)
worldwide and nonalcoholic fatty liver disease (NAFLD) has developed as major etiology of chronic liver diseases,
cirrhosis and eventually HCC in the last decades. Although nucleos(t)ide analogs are recommended as the
first-line drug for patients with chronic hepatitis B, incomplete eradication of HBV serves as an obstacle for
effective cure of chronic hepatitis B and even HCC. NAFLD refers to a spectrum of hepatic metabolic disorders,
compromised with multi-system diseases. Considering the specificity of hepatocytes and enrichment of immune
cells in liver, this review aims to summarize the mechanisms of direct pro-tumorigenesis to hepatocytes induced
by HBV infection and abnormal lipid metabolism, and indirect oncogenic processes mediated by immune cells. We
also discuss similarities and differences of immune cells between HBV- and NAFLD-HCC and finally focus on the
novel immunotherapies concerning preclinical and clinical studies for liver cancer.

Keywords: Hepatitis B virus, nonalcoholic fatty liver disease, hepatocellular carcinoma, immune cells, immunotherapy

INTRODUCTION
Liver cancer is one of the most common causes of cancer-related deaths worldwide, with an estimated of
1.1 million new cases to be diagnosed in 10 years (GLOBOCAN, 2018). Hepatocellular carcinoma (HCC)
accounts for nearly 80% of primary liver cancer and the occurrence is globally gender and geography
biased. The estimated age-standardized incidence rates in men are mostly 3 times than that of women
(13.9/1,000,000 vs. 4.9/1,000,000) in 2018. The high rates in Pacific Asia, West and Central Africa have
persisted for decades, although declining trends have been observed in China and Japan in the past two

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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and indicate if changes were made.

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