Statins for chemoprevention of hepatocellular carcinoma: assessing the evidence

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Date: Aug. 2013
Publisher: Expert Reviews Ltd.
Document Type: Report
Length: 2,437 words
Lexile Measure: 1420L

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Author(s): Abby B Siegel [*] 1 , Hashem B El-Serag 2



hepatocellular carcinoma; prevention; statin

Hepatocellular carcinoma (HCC) incidence rates have tripled in the United States over the last 30 years [1] . HCC has varied etiologies in different populations, including hepatitis B, mostly in Asia and sub-Saharan Africa, and hepatitis C in the West. Metabolic syndrome is becoming an increasingly recognized etiology of HCC worldwide, and may account for up to 30% of cases of HCC in the USA [2] . Hepatitis B vaccination programs have shown reductions in HCC incidence, but for those with other underlying risk factors, primary preventive efforts have been less successful.

About a third of adults in the USA have metabolic syndrome, and rates in Asia are now approaching those in the West [3,4] . Nonalcoholic fatty-liver disease (NAFLD) affects about a third of the US adult population and is the hepatic manifestation of metabolic syndrome. Finally, NAFLD includes a diverse group of liver disorders, ranging from nonalcoholic steatohepatitis to cirrhosis. Those with nonalcoholic steatohepatitis have about a twofold increased risk of developing HCC [5-7] .

Patients with various components of metabolic syndrome may also have higher incidence of and mortality rates from HCC than those without metabolic syndrome [8,9] . For instance, diabetes and obesity both accentuate the risk of HCC in patients with known HCV [10,11] . In animal models, high-fat diets given to mice lead to larger and more proliferative liver tumors [12] . Therefore, one possible reason for their worse outcomes may be that patients with features of metabolic syndrome have more aggressive tumor characteristics, such as increased vascular invasion [13] .

There is biologic plausibility for a benefit of statins in reducing HCC risk, especially for patients with HCV or metabolic syndrome. Statins inhibit the formation of geranylgeranylated protein, necessary for HCV replication [14] , and may augment response to hepatitis C therapy [15] . In patients with underlying heart disease and elevated liver function tests, statin use both reduced cardiovascular events and improved liver function tests, suggesting a benefit in patients with presumed NAFLD [16] . Further, there are several proposed mechanisms that might explain the anticancer effects of statins. Among these, statins prevent post-translational modifications of G-protein subunits, such as RAS [17] . They may also block lymphocyte adhesion and costimulation and have been shown to have proapoptotic effects [18,19] .

Data for statin use in the prevention of other cancers have been conflicting. For instance, a meta-analysis of randomized and observational trials of statin use and breast cancer incidence revealed no significant decrease in cancer risk, although there was a suggestion of possible benefit in long-term users [20] . Colon cancer trials have showed similar inconsistent results. An initial case-control trial by Poynter et al . suggested an almost 50% risk reduction for those taking statins in northern Israel [21] . Nielsen et al . reported a significant decreased in all-cause and cancer-related mortality in statin users in Denmark [22] . Limitations of this report included lack of data on smoking and the fact that no dose-response relationship was seen. However, a meta-analysis including randomized, cohort...

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Gale Document Number: GALE|A341859522