Editorial
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 14, 2011; 17(38): 4258-4270
Published online Oct 14, 2011. doi: 10.3748/wjg.v17.i38.4258
Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma
Yi-Fang Han, Jun Zhao, Li-Ye Ma, Jian-Hua Yin, Wen-Jun Chang, Hong-Wei Zhang, Guang-Wen Cao
Yi-Fang Han, Jian-Hua Yin, Wen-Jun Chang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China
Jun Zhao, Department of Hepatobiliary Surgery, the 3rd Affiliated Hospital, Second Military Medical University, Shanghai 200433, China
Li-Ye Ma, Department of General Surgery, the 1st Affiliated Hospital, Second Military Medical University, Shanghai 200433, China
Author contributions: Han YF and Zhao J collected data, provided interpretation and contributed equally to this work; Ma LY, Yin JH, Chang WJ and Zhang HW critically read the paper; Cao GW wrote the paper.
Supported by National Natural Science Foundation of China, No. 81025015 and No. 30921006
Correspondence to: Guang-Wen Cao, MD, PhD, Professor of Medicine, Chairman, Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China. gcao@smmu.edu.cn
Telephone: +86-21-81871060 Fax: +86-21-81871060
Received: May 12, 2011
Revised: July 12, 2011
Accepted: July 19, 2011
Published online: October 14, 2011
Abstract

Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus (HBV) infection contributes to > 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged > 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8+ T cells and regulatory T cells or Th1 and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Viral load; Genotype; Mutation; Immune cells; Signaling pathway; Cytokine; Prognosis