People with liver fibrosis can see an improvement in their disease after taking interferon-alfa, says a new study from Greece, but those who achieve a sustained virological response (SVR) have the best outcomes.1
Still, even non-responders and those who relapse can see a benefit from the medication, depending on the length of time that they take it, according to doctors in the Academic Department of Medicine at Hippokration Hospital of Athens, Greece.
Clarifying the Mystery
The researchers wanted to learn more about the specific effect that this standard hepatitis therapy has on their patients with fibrosis of the liver. Currently, the only measure of interferon treatment failure or success is a patient's ability to achieve an SVR, or sustained virological response, defined as maintaining undetectable levels of the virus for at least 6 months after therapy is discontinued.
Fibrosis is scarring of the liver that occurs in hepatitis infection. It can potentially progress to cirrhosis, a type of chronic liver disease in which normal cells are damaged and replaced by scar tissue. Cirrhosis ranks as the eighth leading cause of death in the United States.2
"The possible effect of interferon-alfa on liver fibrosis progression has not been adequately studied in chronic hepatitis B,” wrote George Papatheodoridis, MD, and his colleagues.
Comparing Treated with Untreated Patients
In an attempt to come up with more answers, Papatheodoridis' group retrospectively evaluated 147 patients with chronic hepatitis B who were also E antigen-negative. That's a mutant form of hepatitis B that tends to be more resistant to treatment. "In fact, there were suggestions that only nucleoside analogues have a beneficial effect on liver histology" in these patients, explained Papatheordoridis, an associate professor in Medicine and Gastroenterology who led the study, in an interview with Priority Healthcare. Nucleoside analogs like Hepsera (adefovir dipivoxil) and Epivir-HBV (lamivudine) interfere with the activity of an enzyme that the hepatitis B virus uses to make copies of itself.3
One hundred twenty patients had previously been treated with interferon alfa, and the remaining 27 had not. Each patient had undergone at least 2 biopsies previously, as well.
Papatheodoridis and his colleagues found fibrosis improved in about 17 percent of the treated patients, overall, compared to just 4 percent of those who didn't receive therapy. Those who achieved sustained virological responses had the most improvement in liver fibrosis compared to relapsers, who had the worst improvement.
Even Relapsers and Nonresponders Benefited
They also learned that interferon induced a sustained response in 30 patients, but 57 only had an initial response, and then subsequently relapsed. The remaining 33 had no response.
Fibrosis also worsened in about a third of those treated—the worst progression mostly in nonresponders. But that compares to some 70 percent of those who didn't undergo interferon therapy at all, the researchers found.
"The annual rate of fibrosis progression was worse in the untreated than in treated patients," Papatheodoridis and his colleagues wrote, a significant finding, even considering nonresponders and relapsers.
The research team also discovered that several key factors increased the likelihood of fibrosis progression: older age, and worse liver disease or lower fibrosis level at the beginning of this study.
Interferon Benefits Found in All Cases
After collecting their data, the researchers summarized that "interferon alfa significantly reduces the rate of fibrosis progression, but such an effect is mainly observed in patients with sustained biochemical responses." In those who relapse after initial treatment with interferon and in non-responders, the beneficial effect on fibrosis depends on how long treatment is given, they said.
"Sustained off-therapy response should remain the measure of interferon efficacy," Papatheodoridis told Priority Healthcare. "However, we showed that, although sustained off-therapy response is the optimal outcome and results in significant improvement of fibrosis, the worsening of liver fibrosis is slower in patients without such a response (relapsers or non-responders) compared with untreated cases."
Though the benefit for non-responders and relapsers may be temporary, other antiviral agents could be subsequently prescribed, Papatheodoridis explained.
'First Therapeutic Option'
Intron-A is the form of interferon alfa used to treat people with hepatitis B. But it's not necessarily intended for every HBV patient. Those who are chronically infected, have higher liver enzyme levels and actively replicating virus are typical candidates for this therapy. Clinical studies have shown that approximately 45 percent of patients prescribed Intron-A respond to the therapy.4
"We will continue further studies in more detailed aspects of this area," Papatheodoridis said. "I think that our study further strengthens the suggestions that interferon should be the first therapeutic option for patients with HBV E antigen-negative chronic hepatitis B."
1. Papatheodoridis GV, Petraki K, Cholongitas E, Kanta E, Ketikoglou I, Manesis EK. J Viral Hepat 2005 Mar;12(2):199-206.
2. American Liver Foundation. What Are the Diseases that Affect the Liver? Available at: http://www.liverfoundation.org/cgi-bin/dbs/articles.cgi db=articles&uid=default&ID=1043&view_records=1.
Accessed March 11, 2005.
3. Zoulim F, Trepo C. New antiviral agents for the therapy of chronic hepatitis B virus infection. Intervirology 1999;42(2-3):125-44.
4. Hepatitis Neighborhood. HBV Medications: Intron-A, Epivir HBV & Hepsera. Available at: http://www.hepatitisneighborhood.com/content/
treatment_options/medications_for_hepatitis_287.aspx.
Accessed March 11, 2005.
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.
