Hepatitis B experts at loggerheads
Adam Cresswell, Health editor, Milan | May 10, 2008
POOR prescribing habits by liver specialists are creating resistance to the
first drugs able to combat the serious side effects of hepatitis B. And unless
doctors modify their ways, the same thing will happen to drugs introduced to
The warning comes from a top Australian virologist who told an international
meeting of liver specialists that the antiviral drugs adefovir (sold in
Australia as Hepsera) and lamivudine (sold as Zeffix and 3TC) are now
practically useless against hepatitis B due to increased viral resistance to
This has happened, he claims, because doctors frequently prescribe the
medications on their own as "monotherapy", instead of combining them with
other drugs. Since the hepatitis B virus (HBV) mutates very rapidly,
monotherapy has needlessly created resistance by giving a survival advantage
to mutated strains of the virus, less susceptible to suppression by drugs.
Stephen Locarnini, director of the WHO Collaborating Centre for Virus
Reference and Research in Melbourne, told liver specialists, hepatologists,
attending the annual meeting of the European Association for the Study of the
Liver in Milan that the same thing was poised to happen to the newer agents.
To help sidestep the problem, Locarnini called upon pharmaceutical companies
making drugs with activity against hepatitis B to collaborate on studies
designed to establish which medicines best complement each other.
About 160,000 Australians are estimated to be chronically infected with the
hepatitis B virus (HBV). Although people infected as adults clear the virus
naturally in 95 per cent of cases, children and particularly infants are more
susceptible and once the infection becomes chronic it cannot be cured.
Initial infection can be prevented with a vaccine, but the vaccine is of no
use in infected patients. That's because the virus targets cells in the liver
and multiplies rapidly. The body's immune system reacts by killing the
infected cells, and does so so efficiently it can trigger liver inflammation
and, in some cases, cirrhosis and liver cancer.
Locarnini says there's "a big argument" among experts as to whether or not
monotherapy is appropriate. "The hepatologists believe you can get away with
monotherapy. They are in the majority and they win," he said. According to
Locarnini, infectious disease specialists don't see it that way: "I'm a
virologist. I get to see all the resistance that's happening".
According to Locarnini, there are parallels with the development of HIV drugs.
Like HBV, HIV is a fast-mutating virus prone to developing resistance to drugs
used on their own. That's why many HIV patients responded well to treatment
with AZT in the late 1980s, but sickened as the drug lost effectiveness.
Locarnini fears a repeat of the HIV story with emerging Hepatitis B drugs.
Worse, he says that resistance to lamivudine weakens the replacement drug
entecavir, which is approved in Australia, while adefovir resistance weakens
tenofovir, an even newer drug approved in Europe last month and expected to be
approved here later this year.
"What we are really battling at the moment is the education of hepatologists"
says Locarnini. He says this message is seldom welcomed by liver specialists,
who, he says, can "get very pissed off" in response.
Still, he's not on his own. Experts such as Mark Sulkowski, associate
professor of medicine at the Johns Hopkins School of Medicine in Baltimore,
Maryland, support Locarnini's argument.
"Once you have identified resistance in a virus like hep B that cannot be
eradicated, your next treatment is affected by that (resistance)," says
Sulkowski. "Clinicians need to think about resistance before they reach for
the prescription pad. We are not doing that right now. We're reaching for the
first drug on the shelf."