Serum alanine amino transferase flares during interferon treatment of chronic hepatitis B: Is sustained clearance of HBV DNA dependent on levels of pretreatment viremia?

During interferon treatment of chronic hepatitis B, an alanine aminotransfe rase (ALT) flare may herald a sustained loss of viral replication, but the relationship between virologic response, the extent of a flare, and pretrea tment hepatitis B virus (HBV) DNA level has not been defined. We retrospect ively examined the impact of an ALT flare on sustained virologic response i n 121 interferon-treated patients and 42 untreated controls with either low -level (< 100 pg/ mL) or high-level ( greater than or equal to 100 pg/mL) v iremia. The degree of ALT flare was classified as mild (increase in ALT of 86-171 IU/L above baseline), moderate (increase of 172 to 343 IU/L above ba seline), and severe (increase of greater than or equal to 344 IU/L above ba seline). Undetectable serum HBV DNA and hepatitis B e antigen (HBeAg) loss were significantly more likely at the end of follow-up in patients having a flare (P = .0001 and .001, respectively). In the high virerma group, a pro portionate increase in virologic response was observed as the degree of fla re increased. By multivariate analysis, high baseline HBV DNA, high pretrea tment ALT, and both moderate and severe ALT flare were independently predic tive of a virologic response with severe flare being the most powerful pred ictor for a sustained loss of serum HBV DNA (odds ratio, 5.3; P = .004). Se vere flare was predictive of a virologic response in the high but not low v iremia group. We conclude that a virologic response in patients with high-l evel viremia is dependent on the degree of ALT flare. Induction of a robust flare may enhance virologic response when high-level viremia is detected.