People who take interferon therapy for long periods as a treatment for hepatitis may also find that the drug helps prevent liver cancer. That's the claim of a study from Japan that evaluated the medication's effect on hepatocellular carcinoma in a large group of patients with chronic hepatitis C.1
"Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients," wrote the study's lead investigator Yasushi Shiratori, MD, in the department of Gastroenterology, Hepatology and Infectious Diseases at Okayama University in Okayama, Japan, and his colleagues.
HCV's Cancer Connection
Hepatitis C (HCV) is estimated to have infected nearly 4 million Americans, 2.7 million of whom are chronically infected, meaning that they have had it for a long time. The disease can be variable; it winds up becoming serious for some people, but not for others. Most who carry the virus have it for the rest of their lives. Some with liver damage due to the virus may also develop cirrhosis (scarring) of the liver and liver failure, which may take years to progress. Symptoms of the disease include jaundice, fatigue, dark urine, abdominal pain, loss of appetite, and nausea. Interferon and the oral anti-viral drug, ribavirin, are the mainline treatments for HCV.2
Cirrhosis is a complication of liver disease in which hepatocytes (liver cells) become damaged and scarred. This lowers the amount of normal liver tissue, and thus causes liver dysfunction, such as abnormal blood flow through the organ.3 People with cirrhosis also face a higher risk of developing liver cancer, also known as hepatocellular carcinoma.4
According to Shiratori and his associates, it takes approximately 20 years from diagnosis to develop cirrhosis, and about 25 to 30 years to eventually develop cancer of the liver.
Interferon's New Role?
To answer the question about whether interferon therapy taken for several years has an effect on the progression of liver cancer, Shiratori's team recruited 345 patients with chronic hepatitis C and cirrhosis who had been enrolled in other, unrelated clinical trials.
This was not a randomized, controlled trial, however. In the study, 271 patients received 6 to 9 international units (IU) of interferon three times per week for up to 88 weeks (1 year, 9 months). Seventy-four other individuals refused interferon treatment.
During regular follow-ups, the physicians tested for evidence of hepatocellular carcinoma using ultrasound exams and blood tests.
They found that the overall incidence of hepatocellular carcinoma among those treated with interferon during the study was significantly lower than in those who received no therapy. Those who achieved a sustained virologic response (SVR)—defined as no evidence of the virus for at least 6 months after therapy is withdrawn—had even lower odds of developing liver cancer, the Japanese doctors reported.
A total of 69 people died during the follow-up period—17 percent in the group receiving interferon therapy compared to nearly a third of those in the group not receiving treatment, suggesting that the medication also helped improve survival odds for those taking it. Those found to have achieved an SVR had even better chances of survival, Shiratori and his colleagues noted.
"Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival," the investigators concluded.
Other Positive Implications
Results of a clinical trial published 3 years ago were similar.5 Doctors at Ogaki Municipal Hospital in Ogaki, Japan followed 413 chronically infected HCV patients for more than 6 years after they'd been taking interferon therapy.
"Hepatocellular carcinoma was found in 21 patients after interferon therapy," they wrote, which suggested that those who had taken the medication had better odds of avoiding liver cancer altogether.
Common Factors: Age and ALT Levels
The researchers learned that the factor related most directly to the risk of developing liver cancer was the level of alanine aminotransferase (ALT) in each patient, followed by the patient's age. ALT is a liver enzyme that is released into the bloodstream when liver disease occurs. Doctors take tests for ALT to determine if liver disease exists in a certain patient.
In conclusion, the Japanese investigators wrote that interferon therapy had a positive effect on liver cancer risk, and "even if interferon therapy fails to eradicate the hepatitis C virus, maintaining low serum alanine aminotransferase levels post-interferon therapy would reduce the risk of hepatocellular carcinoma in chronic hepatitis C."
1. Shiratori Y, Ito Y, Yokosuka O et al. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med 2005 Jan 18;142(2):105-14.
2. Centers for Disease Control and Prevention (CDC). Viral Hepatitis C. Available at: http://www.cdc.gov/ncidod/
diseases/hepatitis/c/hepcprev.htm. Accessed February 2, 2005.
3. American Liver Foundation. What is Cirrhosis? Available at: http://www.liverfoundation.org/images/
articles/1059/cirrhosis.pdf. Accessed February 2, 2005.
4. American Cancer Society. What Causes Liver Cancer? Available at: http://www.cancer.org/docroot/
cri/content/cri_2_2_2x_what_causes_liver_cancer_25.asp. Accessed February 2, 2005.
5. Hayaski K, Kumada T, Nakano S et al. Incidence of hepatocellular carcinoma in chronic hepatitis C after interferon therapy. Hepatogastroenterology 2002 Mar-Apr;49(44):508-12.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
