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

Abstract

Background and aims: The 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 8,515 PLC patients whose specimens were reserved at the BioBank of the hepatobiliary hospital (Shanghai, China) during 2007–2016. Of those, 3,124 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-year 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-year 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, Barcelona Clinic Liver Cancer (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 population. The contributions of HBV to ICC and other etiological factors to HCC might be indirect via arousing non-resolving inflammation.

Changing trends in the disease burden of primary liver cancer caused by specific etiologies in China

“…Chronic HBV infection in China has been considered to be the most common factor in the etiology of liver cancer and a major contributor to its development . Our study showed that the proportion of liver cancer caused by hepatitis B was approximately 60%, which is significantly lower than previous reports . This difference might be partly explained by that we used the nationwide data instead of the regional data used in previous studies.…”

“…30 Our study showed that the proportion of liver cancer caused by hepatitis B was approximately 60%, which is significantly lower than previous reports. 8,31 This difference might be partly explained by that we used the nationwide data instead of the regional data used in previous studies. To combat HBV, the Chinese government initiated a national immunization program to address the HBV epidemic.…”

Integrative analysis of highly mutated genes in hepatitis B virus‐related hepatic carcinoma

“…Hepatocellular carcinoma (HCC), the major pathological type of liver cancer, is still a leading cause of cancer‐related death worldwide . In Asia and Africa, chronic hepatitis B virus (HBV) infection is the major cause of HCC development . Although it has been suggested that several factors, including the repeated inflammation mediated by immune reactions against the virus, the integration of HBV DNA into the host genome and the virus‐encoded oncoproteins (HBx and preS2/S proteins), are responsible for the development of HCC induced by HBV infection, the molecular mechanisms of hepatocarcinogenesis caused by HBV infection are still not well understanding, and no effective agents have been developed for the treatment of HBV‐related HCC.…”

“…1 In Asia and Africa, chronic hepatitis B virus (HBV) infection is the major cause of HCC development. [2][3][4] Although it has been suggested that several factors, [5][6][7] including the repeated inflammation mediated by immune reactions against the virus, the integration of HBV DNA into the host genome and the virus-encoded oncoproteins (HBx and preS2/S proteins), are responsible for the development of HCC induced by HBV infection, the molecular mechanisms of hepatocarcinogenesis caused by HBV infection are still not well understanding, and no effective agents have been developed for the treatment of HBV-related HCC. Hence, it is extremely important to discover novel molecules involved in the carcinogenesis of HBV-associated HCC and offer the possibility of improving therapeutic approaches for HCC with HBV infection.…”

The role of APOBEC3B in the development of hepatocellular carcinoma should be investigated with the consideration of hepatitis B virus evolution

“…The chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) globally [1] . In Eastern China, chronic HBV infection contributes to 87.5% of HCC whereas chronic hepatitis C virus (HCV) infection contributes to 1.7% [2] . The mortality of HCC has increased in Europe and America over recent decades [3] .…”