A case of breakthrough hepatitis caused by HBV-DNA mutations after 4 years combination therapy of Lamivudine and Adefovir dipivoxil

A 49-year-old man was admitted to our hospital suffering from acute hepatitis exacerbation caused by hepatitis B virus in July 2008. He had been diagnosed as chronic hepatitis B in 1999 and been successfully treated with lamivudine. In 2004, he experienced the first breakthrough hepatitis, which was controlled with an addition of adefovir dipivoxil to lamivudine. On admission, we found the elevation of the serum HBV-DNA level, which was revealed to contain the adefovir dipivoxil-resistant mutations: A181V/T and N236T. Although the appearance of mutations against adefovir dipivoxil has been described in some reports, it was rare that such mutations caused breakthrough hepatitis. We applied him the combination therapy with adefovir dipivoxil and entecavir, which decreased the serum HBV-DNA and alanine aminotransferase concentration within a month.