Fatal Submassive Hepatic Necrosis Associated with Tyrosine‐Methionine‐Aspartate‐Aspartate–Motif Mutation of Hepatitis B Virus after Long‐Term Lamivudine Therapy

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Abstract
We present a case of infection with lamivudine-resistant mutant hepatitis B virus (HBV) that fatally exacerbated hepatitis following the emergence of HBV with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif in an immunocompetent patient who was receiving long-term lamivudine therapy. Restriction fragment length polymorphism analysis showed that the YMDD-motif mutant was the predominant form of circulating HBV at the time of the fatal exacerbation, and a necropsy specimen of the liver revealed submassive hepatic necrosis without steatosis.