Acute exacerbation of chronic hepatitis B virus infection after withdrawalof lamivudine therapy

Acute exacerbations of chronic hepatitis B virus (HBV) infection occur afte r withdrawal of lamivudine therapy in approximately 16% of patients and are considered of little clinical significance. We observed "lamivudine withdr awal hepatitis" accompanied by jaundice and incipient liver failure, but al so followed by complete recovery and viral clearance. To investigate the in cidence, severity, timing, and virologic characteristics of "lamivudine wit hdrawal hepatitis" we monitored 41 patients for at least 6 months after dis continuation of nucleoside analogue therapy. The incidence of hepatitis fla res was estimated to be 7 of 41 (17%); in 2 of 41 cases (5%), hepatitis fla res were associated with jaundice and incipient liver failure. A noticeable feature of the "lamivudine withdrawal hepatitis" flares were the high HBV- DNA levels at the time of the alanine transaminase (ALT) peak. All were wil d-type HBV, even the one that emerged from a lamivudine-resistant strain du ring therapy. To minimize the risk of liver failure and to enhance the elim ination of HBV following flares, lamivudine therapy was reinstituted in an icteric patient. Clinical and biochemical remission ensued, followed by los s of HBV DNA and hepatitis B e antigen (HBeAg) seroconversion. Such a virol ogic response did not occur in 5 other patients with a nonicteric "lamivudi ne withdrawal hepatitis," who were not retreated with lamivudine, Hepatitis after withdrawal of lamivudine resembles acute hepatitis B with a predomin ance of anicteric flares within a time frame of 6 months. Active management of hepatitis flares following withdrawal of nucleoside analogue therapy sh ould be investigated further.