Beyond heart health: Could your statin help prevent liver cancer?

Liver cancer is hard to treat. It’s a top-five cause of cancer-related death worldwide and a growing cause of cancer-related deaths in the United States. Since liver cancer is often found at a late stage, when treatment has limited benefit, there has been increasing interest in prevention. That’s where statin medications might come in.

Liver cancer is usually caused by chronic liver disease, so an important way to prevent liver cancer is to treat the underlying trigger. For example, curing hepatitis C infection — an important cause of chronic liver disease — reduces the risk of liver cancer. However, if the liver disease has progressed to an advanced stage, the risk of liver cancer remains high even after removing the underlying cause.

Statins and liver disease: what’s the connection?

Statin medications are widely known to lower cholesterol levels and decrease the risk of cardiovascular disease. When statins first came on the market, there was great concern that statins might injure the liver. It turns out that not only are significant side effects rare, but statin medications are likely beneficial for the liver. In fact, research has shown that for people with liver disease, statins are associated with a reduced risk of liver failure, liver cancer, and death (see this study, this study, and this study).

It turns out that some statins may be better at preventing liver cancer than others. Specifically, lipophilic statins (those that dissolve more readily in lipids such as oils and fats) may be more effective for preventing liver cancer than hydrophilic statins (those that dissolve more readily in water). This suspected difference is supported by observations that lipophilic statins can more easily get into diseased liver cells, passing readily through cell walls, which are made mostly from lipids. Once inside cells, lipophilic statins may do a better job interfering with cancer formation.

Lipophilic statins include atorvastatin (Lipitor), simvastatin (Zocor), Fluvastatin (Lescol), and lovastatin (Altoprev). Hydrophilic statins include pravastatin (Pravachol) and rosuvastatin (Crestor).

Study links lipophilic statins to reduced risk of liver cancer

A recent study published in Annals of Internal Medicine took a closer look at the effect of different statin types on liver cancer risk. In the largest and most comprehensive study on the topic to date, the study researchers examined liver cancer risk over 10 years in a group of more than 16,000 adults with viral hepatitis (a possible cause of chronic liver disease). Based on records from the Swedish national registry, their results demonstrate that individuals who took a lipophilic statin (in this case atorvastatin or simvastatin) were at a significantly lower risk of developing liver cancer than those who were not taking a statin (3.3% versus 8.1%). In contrast, the study did not find a statistically significant benefit in liver cancer risk for individuals taking hydrophilic statins (rosuvastatin or pravastatin) compared to those not taking a statin. Taking either type of statin was associated with a lower risk of death compared to not taking a statin at all.

As with all studies, this one had some limitations. They include only looking at individuals from Sweden, only those with liver disease from viral hepatitis (as opposed to other causes of liver disease), and having relatively fewer data points for people taking hydrophilic statins, which might have made it harder to find a benefit.

A cause-and-effect relationship?

While a strong connection has been drawn between lipophilic statins and decreased liver cancer risk, research has not yet proven that these medications prevent liver cancer. Demonstrating a cause-and-effect relationship would require a study where people with chronic liver disease are randomized to receive either a lipophilic statin or a control medication.

It is possible that other unmeasured factors could actually account for the observed difference in cancer risk. These factors might include differences in liver disease severity, or other differences in treatment that correlate with statin prescribing patterns. However, the Annals study did demonstrate that higher doses of lipophilic statins were associated with a lower risk of liver cancer, implying a cause-and-effect relationship may indeed be present.

Weigh risks and benefits with your doctor

Further evidence is needed before recommending that individuals take statins specifically for liver disease. While there may be a benefit, there is also a small but real risk of side effects and the consideration of cost.

If you have liver disease and are planning to start a statin for cardiovascular disease, it would be worth discussing with your doctor the risks and benefits of selecting a lipophilic statin such as atorvastatin or simvastatin. In the meantime, ongoing and future studies will help to define the precise role of these medications for preventing liver cancer and the progression of liver disease.

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