Limit lamivudine therapy to patients with moderate to severe

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   Source:  Family Practice News, May 1, 2002 v32 i9 p14(1).
                                                                              
    Title:  Limit lamivudine therapy to patients with moderate to severe
            hepatitis B. (Future Antivirals may be more Effective).
   Author:  Timothy F. Kirn
                                                                              
Subjects:  Lamivudine - Therapeutic use
            Hepatitis B - Drug therapy
Locations:  Canada
SIC code:  8730
                                                                              
Electronic Collection:  A86203859
                   RN:  A86203859
                                                                              

Full Text COPYRIGHT 2002 International Medical News Group

WHISTLER, B.C. -- Lamivudine therapy should still be reserved for hepatitis B patients with persistently elevated alanine arninotransferase levels and
biopsyproven evidence of moderate to severe hepatitis, Dr. Jenny Heathcote said at an update on viral infections sponsored by the University of British Columbia.

Oral antiviral therapy would be more convenient and economical than
interferon, but it appears that the possible complications of treatment do not justify any possible benefit, said Dr. Heathcote, a professor of medicine at the University of Toronto.

Treatment response may not be durable for most patients. Once started,
treatment cannot be stopped if a hepatitis B e antigen (HbeAg)-positive
patient does not seroconvert. With prolonged therapy, liver disease markers that might improve initially begin to deteriorate, and viral mutation becomes more likely. Mutations can be associated with disease exacerbations, reduced likelihood of seroconversion, and an increased risk of reinfection following liver transplantation should the infection necessitate  transplant, she said.

Stopping therapy, however, can result in an acute flare-up of liver disease.
"These flare-ups can be relatively severe," Dr. Heathcote added.

Some studies suggest that response endures for 2-3 years in 86% of
HBeAg-positive patients who seroconvert with treatment. But data from Dr.
Heathcote's patients suggest that the response persists for 2 years in 62% of patients treated for an additional 6 months after seroconversion, the current standard practice. Additional patients probably revert after that, she said.

Patients who lack the hepatitis B e antigen have an even smaller chance of
benefiting from lamivudine. Their response rates are lower and the course of their disease is more variable and more likely to be benign, compared with HBeAG-positive patients. Dr. Heathcote found that 63% of 54 HBeAg-negative patients treated with lamivudine had a complete response, compared with 6% in a placebo group; 9% did not respond at all and 28% had a partial response.

Other studies suggest that 89% of HbeAg-negative patients who respond to a course of lamivudine therapy have relapsed at 3 months.

The strongest indication for lamivudine may be decompensated cirrhosis, she said. In one study, serum albumin levels improved with more than a year of lamivudine therapy, and coagulation time diminished. Several patients came off the transplant list.

Lamivudine also may be better tolerated than interferon by patients with
decompensated cirrhosis.

One study comparing the two therapies found equal efficacy. The study also
showed that a combination of the two drugs might be more effective than either alone, but the difference between monotherapy and combined therapy was small.

Combination and monotherapy need further study, Dr. Heathcote said.

The issue may take a new tack: Newer antivirals are expected to be
significantly more effective than lamivudine, and they may especially be less
likely to trigger viral mutation. Dr. Heathcote said that she has data on
patients treated with adefovir for 130 months, and no serious mutations have been noted.

"We have a lot more drugs coming along the line with greater efficacy than the only drug that we have licensed at the moment, [which is] lamivudine," she said. "So there is hope for our patients right around the corner."
                                                                              
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