Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges

Abstract

Worldwide, hepatocellular carcinoma (HCC) is one of the most common cancers. It is thought that 80% of hepatocellular carcinomas are linked to chronic infections with the hepatitis B (HBV) or hepatitis C (HCV) viruses. Chronic HBV and HCV infections can alter hepatocyte physiology in similar ways and may utilize similar mechanisms to influence the development of HCC. There has been significant progress towards understanding the molecular biology of HBV and HCV and identifying the cellular signal transduction pathways that are altered by HBV and HCV infections. Although the precise molecular mechanisms that link HBV and HCV infections to the development of HCC are not entirely understood, there is considerable evidence that both inflammatory responses to infections with these viruses, and associated destruction and regeneration of hepatocytes, as well as activities of HBV-or HCV-encoded proteins, contribute to hepatocyte transformation. In this review, we summarize progress in defining mechanisms that may link HBV and HCV infections to the development of HCC, discuss the challenges of directly defining the processes that underlie HBV-and HCV-associated HCC, and describe areas that remain to be explored.

Impact of Chronic Hepatitis B and Hepatitis C on Adverse Hepatic Fibrosis in Hepatocellular Carcinoma Related to Betel Quid Chewing

“…The well-known environmental risk factors for HCC include chronic infection with the hepatitis B virus (HBV) and hepatitis C virus (HCV) (Bouchard and Navas-Martin, 2011;El-Serag, 2012) and habitual betel quid (BQ) chewing (Tsai et al, 2001(Tsai et al, , 2004IARC, 2004;Secretan et al, 2009;Hamed and Ali, 2013). However, the pathogenic mechanisms about HCC related to BQ chewing remain to be determined.…”

“…Persistent hepatic inflammation is a hallmark of habitual BQ chewing (Sarma et al, 1992;Lin et al, 2008;Angadi and Rao, 2011) and/or chronic HBV/HCV infection (Bouchard and Navas-Martin, 2011;El-Serag, 2012). Hepatic fibrosis, or cirrhosis, is a common end-stage condition of many chronic liver diseases (Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;El-Serag, 2012).…”

“…Persistent hepatic inflammation is a hallmark of habitual BQ chewing (Sarma et al, 1992;Lin et al, 2008;Angadi and Rao, 2011) and/or chronic HBV/HCV infection (Bouchard and Navas-Martin, 2011;El-Serag, 2012). Hepatic fibrosis, or cirrhosis, is a common end-stage condition of many chronic liver diseases (Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;El-Serag, 2012). During fibrosis progression, hepatocellular damage and inflammation trigger complex cellular events that result in collagen deposition (Angadi and Rao, 2011;Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;ElSerag, 2012;Kong et al, 2012).…”

“…Hepatic fibrosis, or cirrhosis, is a common end-stage condition of many chronic liver diseases (Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;El-Serag, 2012). During fibrosis progression, hepatocellular damage and inflammation trigger complex cellular events that result in collagen deposition (Angadi and Rao, 2011;Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;ElSerag, 2012;Kong et al, 2012). Serial liver biopsies are the current gold standard to evaluate the progression of fibrosis.…”

“…Cirrhosis itself is a preneoplastic lesion of HCC. The hallmark of these two premalignant diseases is fibrosis (IARC, 2004;Angadi and Rao, 2011;Bouchard and Navas-Martin, 2011;ElSerag, 2012) The risk for HCC increased with severity of liver injury and adverse fibrosis or cirrhosis (Bouchard and Navas-Martin, 2011;Luedde and Schwabe, 2011;ElSerag, 2012;Kong et al, 2012 ). Habitual BQ chewing has been documented as an independent risk factor for HCC (Tsai et al, 2001(Tsai et al, , 2004IARC, 2004;Hamed and Ali, 2013).…”