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More on Metformin and Statins: Drugs Approved by the FDA for Other Purposes That May Prevent Liver Cancer

From HBF’s expert Guest Blogger, Dr. Thomas London

In an earlier blog, I pointed out that the available drugs to treat or prevent primary liver cancer (hepatocellular carcinoma, HCC) have been disappointing.  I noted that there may be drugs used for other purposes that may work against HCC.  The most promising of these was an old drug called metformin that has been used to treat type II diabetes for 17 years.  Now a new study on metformin provides the most intriguing results yet.

At the 2012 Digestive Disease Week meeting in San Diego, an enormous study from Taiwan was reported that encompassed almost all of Taiwan’s 23 million people. (I am indebted to Christine Frangou for her excellent report in Gastroenterology and Endoscopy News and have quoted from it extensively.) The investigators used the Taiwan National Insurance Database to identify all cases of HCC diagnosed from 1997 to 2008. There were 97,430 patients with HCC (most of whom would have had chronic hepatitis B). They were compared with 200,000 controls matched to the HCC cases by age, gender, and date of first physician visit.  Using the same database they linked all patients with diabetes and their treatment methods to patients with and without HCC.

From this they were able to show that patients with diabetes had a 2.3-fold increased risk of developing HCC.  In those patients who were taking metformin, however, HCC occurred about 20% less often than in those who were not treated with metformin. Furthermore, the longer patients took metformin, the lower their risk of HCC; about 7% lower for each year that they took the drug.

This study is not the final answer.  We don’t know why some diabetic patients were treated with metformin and some were not.  It is possible that the patients who did not take metformin had some unknown liver abnormality and were deliberately not treated with metformin.  Nevertheless, anti-tumor effects of metformin in experimental animals and in cell culture systems continue to be reported.  I will keep my eye out for more research on metformin and HCC and report it as it hits the medical press.

Statins are another group of drugs that are in common use. They were first approved by the FDA in 1987 to lower serum cholesterol levels and thereby prevent heart disease.  Statins inhibit an enzyme in the liver used to make cholesterol.  Several isolated reports suggested that statins might also help prevent HCC.  This month investigators at the Mayo Clinic in Rochester, Minnesota reported a meta-analysis (a statistical method to combine results from different studies) of all the reports in the medical literature of new cases (incidence) of HCC and exposure to statin therapy.  Ten studies reporting a total of 4,928 HCC cases in 1,459,417 patients were analyzed.  Overall, patients who were treated with statins had a 40% lower risk of developing HCC than those who were untreated.  The results varied from population to population. Asian populations which were more likely to also have chronic hepatitis B, had a 50% lower risk of developing HCC, while western populations had about a 30% lower risk.

At this time we do not know what the mechanism of a preventative effect of statins on HCC might be.  Nor do we know whether statins might have been withheld from patients with high cholesterol levels because they had a liver abnormality. It is likely, however, that more information on these issues will become available in the near future.  When that happens I will report it to you.

 

Statins May Prevent Liver Cancer For Those With HBV

Good news for those with chronic hepatitis B that are taking cholesterol-lowering statins.  Results published in Jan. 23 Journal of Clinical Oncology show statins may actually lower the risk of liver cancer for those living with chronic HBV in a dose dependent manner. The study monitored 33,413 hepatitis B patients for hepatocellular carcinoma (HCC) between 1997 and 2008 and tracked the number of HCC cases since 1999.

These are important findings because chronic hepatitis B significantly increases the risk of liver cancer, which causes 80% of primary liver cancers (HCC) worldwide. In the U.S., HCC is the second deadliest cancer with a five year survival rate of less than 10%. Those with chronic HBV are 100 times more likely to develop liver cancer than those without HBV. There are a number of contributing risk factors such as age, gender, ethnic background, family history, smoking history, and extent of liver damage. Despite the known risks, it is impossible to predict without regular liver cancer screening.  Be sure to discuss the guidelines for liver cancer screening with your doctor, as there are specific risk factors that may make monitoring sooner and more frequent, important.  Make liver cancer screening part of your bi-annual or annual monitoring of your HBV and liver health.

So, how do statins reduce the risk of liver cancer for those with Chronic HBV?  The mechanism has not been determined and will require further study.  Statins may reduce the risk of HCC, but it is important to carefully discuss the use of statins with your liver specialist and other treating physicians. Monitoring of your liver enzymes while taking statins is important for those without HBV, but it is even more critical if you have HBV.  Start with a baseline of your liver enzymes (ALT/AST) before beginning statin use, followed by testing at 6 and 12 week intervals.  You want to ensure your ALT/AST levels do not increase by more than three times the upper limits of normal.  Any spikes in your ALT/AST levels will likely occur in the first three months of statin use.  Elevated levels may require a discontinuation of one statin and a simple switch to another.  With the help of your treating physician(s) you will determine what is best for your unique situation to ensure the benefits of statin use outweigh the risks.

And if you are taking a daily statin, don’t forget the importance of eating a well-balanced diet. Sitting down to a big-ole cowboy steak with your statin is probably not what the doctor had in mind when he prescribed cholesterol-lowering medication!