Patients prescribed Hepsera as a therapy for hepatitis B (HBV) over the long term may find it beneficial, report doctors in a recently unveiled clinical trial.1 But the study's lead researcher points out that treatment shouldn't necessarily be prescribed immediately after diagnosis for all patients. Instead, it depends on a number of factors.
Long-Term Efficacy Tested
The investigators recruited nearly 200 patients for the trial, lasting 192 weeks. The patients were selected from a previous 48-week randomized, controlled clinical trial to test Hepsera, also known by its generic name, adefovir dipivoxil (ad-EH-foh-veer dih-pih-VOX-ihl).
The patients in this study were infected with a type of HBV known as hepatitis B e antigen-negative (HBeAg-) chronic HBV. This involves a mutated type of virus that experts have described as being more resistant to therapy.2
Despite that, chief investigator Jenny Heathcote, MD, head of the Clinical Studies Resource Center at Toronto Western Research Institute, and her colleagues found that those given regular, 10-milligram doses of the medicine over the 4-year study period resulted in "prolonged HBV DNA suppression and sustained ALT normalization." Tests that search for evidence of hepatitis B look for its genetic material, or HBV DNA. ALT is the abbreviation for alanine aminotransferase (AL-uh-neen uh-meen-oh-TRANZ-fer-aze), an enzyme that, when released by the liver into the bloodstream, is an indicator of liver disease or damage.3 Thus, normal ALT levels show doctors that your liver disease has stabilized.
How Hepsera Fights HBV
Hepsera is in a class of medications known as nucleotide analogs. It works by blocking a crucial enzyme known as HBV DNA polymerase that the hepatitis B virus uses to make copies of itself and expand its infection in the body.4 The oral drug was approved by the FDA in 2002 as a therapy for people with chronic hepatitis B who have active virus in their blood, high levels of liver enzymes, and evidence of liver damage.5
Experts have described its success in patients with the mutated hepatitis B e antigen-negative form of the virus, as well as the classic positive form.6
But in an interview with Priority Healthcare, Heathcote stressed that adefovir shouldn't be prescribed in all cases of HBV. Patients should be tested for the extent of liver disease by undergoing a biopsy first, she said, adding that viral load should not be the sole basis for drug therapy. "And it's only if the liver biopsy suggests evidence of progressive disease that you then want to introduce treatment in the face of viremia," she said. "There is no direct correlation between disease severity and viral load."
How Hepsera Performed
The study was performed on an "open-label" basis, meaning both patients and clinicians were advised of the medication being tested. The median age of the patients was 47 years. At the start of the study, the study authors reported 81 percent of the patients were men, 70 percent were Caucasian, and about one-quarter of them were Asian. Each patient had been diagnosed with HBV e (HBeAg) antigen negative chronic hepatitis B. Of the original patients enrolled, 70 of them continued on Hepsera treatment to week 144, and 67 finished the study at week 192.
The patients were selected at random to receive either doses of Hepsera or a non-therapeutic placebo. Each patient underwent a liver biopsy to determine the extent of their hepatitis in the 48th week of the study, then were randomized a second time. At the end of the 4-year trial, patients were then given the option to continue on 10 mg doses of Hepsera for an additional year.
When the study concluded, the investigators reported an average drop in viral levels in the patients taking the medication of more than 1000-fold (-3.71 log 10 copies per mL). Four-fifths of them had undetectable levels. Most also saw their liver enzymes return to normal, indicating their liver damage had stabilized.
None of the patients showed resistance to the drug after 48 weeks, but that had climbed to 3 percent of the patients at week 96. Eighteen percent had drug resistance at the end of the study. Still, the investigators wrote," Adefovir dipivoxil was generally well-tolerated with long-term treatment." According to one of the authors, higher levels of HBV DNA one year after starting treatment generally predict drug resistance by the third year of therapy.
The study concluded that maintaining Hepsera treatment in people with hepatitis B can be safe and effective, given the sustained reductions in viral load and levels of ALT. While resistance did crop up, the investigators were optimistic that it was delayed over time. Additionally, rates of resistance will likely diminish in the future once more therapies are licensed and prescribed in combination, Heathcote predicted, similar to the "cocktail" of drugs currently prescribed for people with HIV.
The study was sponsored by Gilead Sciences, which employs at least one of the investigators as consultants and manufactures Hepsera.
1. Hadziyannis S, Tassopoulos N, Chang TT et al. Adefovir dipivoxil (ADV) demonstrates sustained efficacy in HBeAg-chronic hepatitis B (CHB) patients. Digestive Disease Week 2005. 2005 May 14-19. Chicago, IL.
2. Lagget M, Rizzetto M. Current pharmacotherapy for the treatment of chronic hepatitis B. Expert Opin Pharmacother 2003 Oct;4(10):1821-7.
3. Renner EL, Dallenbach A. Increased liver enzymes: what should be done? [Translated from German]. Ther Umsch 1992 May;49(5):281-6.
4. Gilead Sciences. Hepsera Prescribing Information.
5. Food and Drug Administration. Hepsera Consumer Information. Available at: http://www.fda.gov/cder/consumerinfo/druginfo/hepsera.HTM. Accessed June 9, 2005.
6. Yuen MF, Lai CL. Adefovir dipivoxil in chronic hepatitis B infection. Expert Opin Pharmacother 2004 Nov;5(11):2361-7.
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.
