Improved understanding of risk factors could help to reduce the incidence of hepatocellular carcinoma.

Using data from the Taiwan National Health Insurance Research Database, Tsan and colleagues identified over 33,000 patients who had been infected with hepatitis B virus (HBV).1 These patients had been followed for 11 years (1997-2008), and the subset of patients who developed hepatocellular carcinoma (HCC) during this period was identified. Tsan and colleagues then extracted data on statin usage and assessed the relationship between statin usage and liver cancer in this HBV-infected population.1 A total of 1,021 patients in the study cohort developed cancer, and the incidence of liver cancer during the follow-up period was lower among those who had used statins. This study noted that this association between statin use and HCC risk was dose-dependent, with longer durations of statin use being associated with lower incidences of cancer. While these findings are intriguing, future mechanistic research is needed to explain this association. If statins can reduce the risk of cancer in high-risk patients such as those infected with HBV, then these drugs may also reduce the risk of HCC in a broader patient population. While suggesting that statins may have benefit in some patients, this conclusion does not mean that clinicians should treat all patients with statins, as a small percentage of patients will develop liver toxicity or muscle toxicity due to these drugs. Indeed, clinicians who are caring for patients with chronic liver disease may be reluctant to use statins in some instances due to concerns about an increased risk of statin-induced liver damage in these patients. In fact, some of the patients included in the study by Tsan and coauthors may have not received statins because their physicians were influenced by such concerns.1 This caveat should be kept in mind when considering the limitations of this particular study. Another caution regarding this study is that it is a retrospective study based on a database review; such study designs always include the possibility of retrospective bias. A second limitation of this study is that the database used to gather information on statin usage was only established in January 1997, so information about statin use prior to that time was not included in the analysis. Thus, this study was not able to distinguish between first-time prescriptions for statins and continuation of therapy started prior to 1997. Also, the study by Tsan and coworkers does not include information about when statins were used during the 10-year follow-up period.1 Finally, this study showed a dose-response depending on the duration of statin use, with varying reductions in HCC risk among patients who used statins for less than 28 days, 28-90 days, 91-365 days, or greater than 1 year. For example, this study showed a 34% reduction in cancer among patients who had used statins for 28-90 days and a 66% reduction among patients who used statins for over 365 days. However, I find it implausible that cancer rates would be reduced with only 3 months of statin use. While clinicians should keep these considerations in mind when reviewing this study's results, the analysis by Tsan and colleagues has several strengths.1 First, it used a very large database, which improves the statistical power of the results. Also, it used computer-based information to determine which patients were infected with HBV, who subsequently developed liver cancer, and who were using statins during the course of the observation period.