Causes of and Prevention Strategies for Hepatocellular Carcinoma

Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
Seminars in Oncology (Impact Factor: 3.9). 08/2012; 39(4):374-83. DOI: 10.1053/j.seminoncol.2012.05.006
Source: PubMed


Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance. It is associated with a high rate of mortality and its prevalence in the United States and in Western Europe is increasing. Cirrhosis is the strongest and the most common known risk factor for HCC, usually due to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Given the continuing increase in the prevalence of obesity and diabetes, the incidence of non-alcoholic steatohepatitis-related HCC may also be expected to increase, and a potential role of behavior treatment and/or insulin-sensitizing drugs can be envisaged. Vaccination against HBV is the most efficient primary prevention measure currently available to reduce the HCC incidence and mortality in high-incidence areas, while data on the role of interferon (IFN) and nucleos(t)ide analogues (NUC) are still controversial. The pooling of data from the literature suggests a slight preventive effect of antiviral therapy on HCC development in patients with HCV-related cirrhosis, but the preventive effect is limited to sustained virological responders.

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Available from: Marcello Maida, Sep 30, 2015
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    • "Despite the many policy options that could have a positive impact, liver cancer is often neglected in general cancer control plans (Momin and Richardson 2011), and few countries have implemented comprehensive plans for the control of liver cancer along the lines of what has been advocated for cervical [World Health organization (WHO 2006)] and breast cancer control (Breast Health Global Initiative 2008). Given the diverse and synergistic causes of liver cancer, the most promising approach would incorporate strategies to prevent liver cancer of all aetiologies alongside effective targeted screening and early intervention (Cabibbo et al. 2012). "
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    ABSTRACT: The World Health Organization offers clear guidance on the development of national cancer control programmes based on a country's level of resources, yet the motivation to implement such programmes may be driven by factors other than resources.
    Health Policy and Planning 06/2014; 30(5). DOI:10.1093/heapol/czu044 · 3.47 Impact Factor
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    • "De novo lipogenesis is responsible for more than 30% of hepatic fat [7] [8], and dietary lipid contributes ~10% of the hepatic lipid content [7]. The development of hepatic steatosis has the potential to progress through the more aggressive form of hepatic injury [9]. Although effective treatments are important in controlling hepatic steatosis, there are as yet no reliable forms of early diagnosis and prevention. "
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    ABSTRACT: Background & aims: While non-alcoholic fatty liver disease (NAFLD) is the most common risk factor of chronic liver disease, the mechanisms that initiate its development are obscure. Hepassocin (HPS) is a hepatokine that has been reported to be involved in liver regeneration. In addition to the mitogenic activity of HPS, HPS expression is decreased in patients with hepatoma. However, the role of HPS in NAFLD is still unknown. Methods: A total of 393 subjects with (n=194) or without (n=199) NAFLD were enrolled to evaluate the serum HPS concentration. In order to clarify the causal inference between HPS and NAFLD, we used experimental animal and cell models. Hepatic overexpression or silencing of HPS was achieved by lentiviral vector delivery in mice and lipofectamine transfection in HepG2 cells. Lipogenesis related proteins were detected by Western blots. The expression of inflammatory factors was determined by real-time polymerase chain reaction. Results: Subjects with NAFLD had a higher serum HPS concentration than those without it. Overexpression of HPS increased hepatic lipid accumulation and NAFLD activity scores (NAS), whereas deletion of HPS improved high fat diet-induced hepatic steatosis and decreased NAS in mice. Additionally, oleic acid, a steatogenic reagent, increased HPS expression in hepatocytes. Furthermore, overexpression of HPS in HepG2 cells induced lipid accumulation through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent pathway, whereas deletion of HPS decreased oleic acid-induced lipid accumulation. Conclusions: The present study provides evidence that HPS plays an important role in NAFLD and induces hepatic lipid accumulation through an ERK1/2-dependent pathway.
    Journal of Hepatology 06/2013; 59(5). DOI:10.1016/j.jhep.2013.06.004 · 11.34 Impact Factor
  • 02/2013; 2(1):1-3. DOI:10.3978/j.issn.2304-3881.2012.09.01
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