AUTHOR=Yang Fan , Ma Longteng , Yang Yuan , Liu Wenbin , Zhao Jun , Chen Xi , Wang Mengchao , Zhang Hongwei , Cheng Shuqun , Shen Feng , Wang Hongyang , Zhou Weiping , Cao Guangwen 

TITLE=Contribution of Hepatitis B Virus Infection to the Aggressiveness of Primary Liver Cancer: A Clinical Epidemiological Study in Eastern China

JOURNAL=Frontiers in Oncology

VOLUME=Volume 9 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00370

DOI=10.3389/fonc.2019.00370

ISSN=2234-943X

ABSTRACT=Background & Aims: Contribution of hepatitis B virus (HBV) infection to the aggressiveness of primary liver cancer (PLC) remains controversial. We aimed to characterize this in Eastern China.
Methods: We enrolled 8515 PLC patients whose specimens were reserved at the BioBank of the hepatobiliary hospital (Shanghai, China) during 2007-2016. Of those, 3124 who received primary radical resection were involved in survival analysis. A nomogram was constructed to predict the survivals using preoperative parameters.
Results: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular cholangiocarcinoma (CHC) accounted for 94.6%, 3.7%, and 1.7%, respectively. The rates of HBV infection were 87.5%, 49.2%, and 80.6%, respectively. HBV infection was significantly associated with 10 years earlier onset, more cirrhosis, higher α-fetoprotein, higher carbohydrate antigen 19-9 (CA19-9), more microvascular invasion (MVI), lower neutrophil-to-lymphocyte ratio (NLR), and lower platelet-to-lymphocyte ratio (PLR) in HCC. HBV infection was also associated with 7 years earlier onset, more cirrhosis, higher α-fetoprotein, more MVI, and lower PLR in ICC. In the multivariate Cox analysis, high circulating HBV DNA, α-fetoprotein, CA19-9, NLR, tumor size, number, encapsulation, BCLC stage, and MVI predicted an unfavorable prognosis in HCC; only CA19-9 and BCLC stage, rather than HBV-related parameters, had prognostic values in ICC. A nomogram constructed with preoperative HBV-related parameters including HBV load, ultrasonic cirrhosis, and α-fetoprotein perform better than the current staging systems in predicting postoperative survival in HCC. 
Conclusion: HBV promotes the aggressiveness of HCC in Chinese. Contributions of HBV to ICC and other etiological factors to HCC might be indirect via arousing non-resolving inflammation.