Lecture: HBV drug resistance patterns

This lecture focused on the drug resistance patterns in hepatitis B viral infection.  There are at least five recognized mutation patterns, and it is important to recognize drug resistance when it appears.  Typically, while a patient is on therapy and a mutant strain arises, the viral load will increase by > 1 log.  This is followed by a rise in ALT.  Therefore, DNA and ALT levels should be checked at 3 or 6 month intervals.

If a patient is on lamivudine monotherapy, it is generally accepted that a second agent should be added to, rather than substituted for lamivudine.  If a patient is on a highly potent agent, such as entecavir or tenofovir, and develops side effects within the first six months of therapy, it is safe to discontinue (and substitute another agent) rather than add or bridge therapy with a second agent.

For patients who have active, HBV e-antigen negative disease (ie. precore mutation) the only reliable way to allow eventual cessation of treatment appears to be with the use of interferon-based therapy, with the specified goal of seroconverting the surface antigen into surface antibody.  It does not appear that there will be any new agents for the treatment of HBV infection in the next 3 to 5 years, so you should get comfortable with the current arsenal!

For an overview of the molecular genetics of HBV, click on the link below:

http://www.ncbi.nlm.nih.gov/pubmed/21041899

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