Hep B Talk is pleased to introduce Guest Blogger W.Thomas London, MD. Dr. London is internationally renowned for his many decades of work on hepatitis B and liver cancer, which started with his joining the research team that discovered the hepatitis B virus. Dr. London has been at the forefront of liver cancer prevention and has written extensively about hepatitis B from the perspective of an epidemiologist, a clinician and a virologist. As founder and director of the Liver Cancer Disease Prevention Division at Fox Chase Cancer Center in Philadelphia, PA, he developed one of the first successful community-based strategies to help people reduce their cancer risk through the early detection of chronic HBV infection. Dr. London has received the Distinguished Interdisciplinary Research Award from the American Cancer Society and the Distinguished Scientist Award from the Hepatitis B Foundation where he currently serves as Vice-Chair of the Board and as the Senior Medical Advisor.
Liver cancer, hepatocellular carcinoma (HCC), is the 3rd most common cause of death in the world. Little attention was paid to HCC in the United States until recently because it was thought to be rare, but now it is one of the few cancer types that is rising in incidence (number of new cases per year). It is now the most rapidly increasing cancer in men in the US. The prognosis of HCC is poor; one year survival in the United States from the time of diagnosis is only 50%. Detection of tumors when they are very small, less than 2 cm in diameter, and can be removed surgically is the best chance for cure. Liver transplantation is often done if there is more than 1 tumor and the cancers are less than 3 cm in diameter. Unfortunately, most HCCs are diagnosed when they are too large for successful surgical resection or transplantation.
Chemotherapy for HCC has been disappointing. Recently, the drug, Sorafenib (Nexavar), has been shown to be active against HCC, but it only extended survival time by a few months. Thousands of drugs have been developed by the pharmaceutical industry for a great variety of conditions. Of these, 983 have approved by the FDA. That is they were tested in clinical trials, found to be safe and were beneficial for the purposes that they were approved
Scientists at the Hepatitis B Foundation and elsewhere have raised the question, are there drugs on the currently approved FDA list that are used for other purposes that might have a role in the treatment or prevention of HCC? Recent publications suggest 2 candidates. One is metformin (Glucophage), which is derived from the French lilac, and has been used in Europe since 1958 to treat Type 2 diabetes and in the United States since 1995. The other is propranalol, which is used to treat patients with cirrhosis who have varicose veins in the lower end of their esophagus (esophageal varices).
Diabetes is a recognized risk factor for HCC, particularly in persons who are obese and have a fatty liver. (Diabetics are also at increased risk of acquiring hepatitis B). Because patients with diabetes are often treated with metformin, investigators in China and France have looked at whether treatment with metformin lowers the risk of developing HCC. By examining the records of diabetic patients who were treated with metformin or not, they observed that the risk of HCC was lower in the treated patients. Furthermore, an experimental study of liver cancer in mice showed that metformin reduced the number and size of liver tumors.
Propranolol is used to lower the pressure in the portal vein and thereby in esophageal varices. A group of physicians in France looked at the occurrence of HCC in patients with hepatitis C and esophageal varices who received propranolol treatment and those who did not. There was about a 75% reduction in the incidence of HCCs in the propranolol treated patients. Propranolol blocks receptors for epinephrine (adrenalin) and nor-epinephrine on cells in the body. Such receptors are particularly rich on the surface of tumor cells, including HCCs. Experimentally propranolol has been effective in reducing the size and number of several different kinds of tumors.
The studies that have been done so far are intriguing, but they are not conclusive. Neither drug has been studied in a clinical trial to either treat established HCCs or to prevent HCC from occurring in the first place. Such studies are in the planning stages. Keep watching for progress on this front.