Hepatitis B Virus-Associated Hepatocellular Carcinoma

Abstract

Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.

Can next-generation humanized mice that reconstituted with both functional human immune system and hepatocytes model the progression of viral hepatitis to hepatocarcinogenesis?

“…Hepatocellular carcinoma (HCC) is increasing in incidence and is one of the major causes of cancer-related death. Cirrhosis due to chronic viral hepatitis (HBV and HCV) remains the leading cause of the disease worldwide (1)(2)(3)(4). Liver cirrhosis causes the accumulation of progressive gene mutations that can lead to cancer (68, 69).…”

“…HBV chronic infection also plays direct oncogenic effects by expressing oncogenic proteins, insertional mutagenesis, and causing chromosomal instability (69,70). Whether HCV infection plays a direct oncogenic role in HCC development remains debated (1)(2)(3)(4). Humanized mice that can model the human-specific development of HCC from chronic HBV or HCV infection will be highly valuable.…”

“…Globally, ∼500 million people are chronically infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV). These chronic infections cause disordered immune responses, progressively resulting in liver immunopathogenesis and diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinomas (HCC) (1)(2)(3)(4). Although the burden of alcohol-and NASH-related HCC is increasing, chronic hepatitis (HBV or HCV) remains a major cause of HCC development worldwide (1)(2)(3)(4).…”

“…These chronic infections cause disordered immune responses, progressively resulting in liver immunopathogenesis and diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinomas (HCC) (1)(2)(3)(4). Although the burden of alcohol-and NASH-related HCC is increasing, chronic hepatitis (HBV or HCV) remains a major cause of HCC development worldwide (1)(2)(3)(4). Hepatotropic HBV and HCV only infect humans and primates, limiting the availability of animal models for studying virus infection and viral-specific immune responses in vivo.…”

Oral and Periodontal Implications of Hepatitis Type B and D. Current State of Knowledge and Future Perspectives

“…Once infected, symptoms may develop from 30 to 180 days later [ 20 , 21 ]. If entering a chronic phase, the infection can lead to life-threatening complications, including cirrhosis or hepatocellular carcinoma [ 22 ].…”