Pegylated, or longer-lasting, interferon combined with the antiviral medicine, ribavirin, is considered the standard therapy today for people with hepatitis C (HCV).1 For those with hepatitis B (HBV), common therapies include interferon (Intron A), adefovir dipivoxil (Hepsera), lamivudine (Epivir-HBV), or entecavir (Baraclude).2
Now, medical scientists are investigating the potential of a new class of protein known as interferon lambda that they say may induce an antiviral response against both hepatitis B and hepatitis C. They describe the potential of this newly discovered protein in an article published in the Journal of Virology earlier this year.3 So far, though, they stress their findings are inconclusive.
How Interferons Work
Interferons are proteins produced naturally in the body in response to viral infections. These interferons have antiviral activity. Interferon alfa is the primary type used in treatment for hepatitis today. Treatment consists of a recombinant, or reconstructed, form of natural interferon alfa. Pegylated interferon is a modified form of interferon alfa that consists of a large, inert molecule of polyethylene glycol. Modifying the interferon in this way lengthens its half-life in the body, making it more effective. This also requires fewer doses.4
Interferons work in several different ways. They attach to healthy cells in the body and help them defend themselves against the virus, and they boost the immune system's attack against the virus. Finally, interferons also help the body get rid of infected cells.5
But interferon lambda doesn't fall in this category, explained study investigator Michael Robek, PhD, in the Department of Pathology at Yale University, in an interview with Priority Healthcare. "Interferon lambda has been described as an 'interferon-like' protein," he said.
It doesn't bind to cells at the same location as other interferons, but it does possess antiviral activity and is activated by viral infection. "Interferon lambda, in turn, induces the expression of genes with antiviral activity," Robek explained.
Hepatitis Onslaught
Robek and his colleagues at the Scripps Research Institute in La Jolla, California began an in-vitro study using liver cells from mice to test the effectiveness of interferon lambda against hepatitis B. HBV gene activity was induced in the cells, and then were treated with doses of interferon lambda.
The study team found that this novel therapy "inhibited HBV replication greater than 90% at 24 hours after the interferon addition." The study team also discovered that the effectiveness of this treatment was similar to that of interferon beta, a naturally-produced protein in mice that possesses antiviral properties and helps boost immune responses during hepatitis infections. Though the exact method by which interferon lambda attacked the virus in the liver cells isn't exactly known, the study authors speculate there may be an indirect mechanism it uses to stimulate the production of other interferons that attack the virus. They also believe that it may activate genes that, in turn, attack the virus.
Next, the investigators wanted to see if interferon lambda was just as effective against HCV. The researchers treated human liver cancer cells containing hepatitis C virus with doses of interferon lambda for up to 5 days. They found that the therapy reduced HCV levels up to 99%.
Study Caveat
Despite the apparently positive findings, Robek stressed that in a study using live mice, he and his colleagues found interferon lambda to be less effective than the other interferons. Thus, their findings are still inconclusive. "There are some important differences between the mouse and human proteins (humans have 3 interferon-lambda genes, but mice have only one gene, which corresponds to the least active human form) that make any firm conclusions difficult," he said.
As such, there are more questions to answer, including whether interferon lambda might act synergistically with other interferons in treating hepatitis.
Answering these questions could result someday in a treatment consisting of interferon lambda as monotherapy, or prescribed in combination with interferon alfa, the study researchers speculated. "Further studies will be needed to determine if these therapeutic strategies will be feasible."
What Differences Does This Protein Possess?
Robek says he and his associates have launched further research of their own. They're studying the differences in interferon lambda activity in the lab versus in mice. "We are also determining whether interferon lambda can act synergistically with other interferons to inhibit virus replication," he explained.
Even if it is later confirmed that interferon lambda is not as effective at attacking the hepatitis virus as interferon alfa, it's possible that it could become a treatment option at some level because it may cause fewer side effects, Robek stressed. "Also, the possibility may exist to use combinations of interferons that, together, are more active than either alone. We don't have any evidence for either of these, but both are possible," he said.
1. National Institutes of Health. Consensus Development Conference Statement. Management of Hepatitis C: 2002. 2002 Jun 10-12.
2. Hepatitis Neighborhood. HBV Medications: Intron-A, Epivir-HBV, Hepsera & Baraclude. Available at: http://www.hepatitisneighborhood.com/content/treatment_options/
medications_for_hepatitis_287.aspx. Accessed Jun 2,2005.
3. Robek MD, Boyd BS, Chisari FV. Lambda interferon inhibits hepatitis B and C virus replication. J Virol 2005 Mar;79(6):3851-4.
4. National Digestive Diseases Information Clearinghouse. National Institutes of Health (NIH). Chronic Hepatitis C: Current Disease Management. Available at: http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm#H. Accessed June 2, 2005.
5. Hoffmann-La Roche Pharmaceuticals. How is Hepatitis C Treated? Available at: http://www.pegasys.com/treatment/how.asp. Accessed June 2, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
