Updated longitudinal data on acute exacerbation of chronic hepatitis B in patients with breast cancer receiving anthracycline-based adjuvant chemotherapy: therapeutic vs. pre-emptive use of lamivudine.

OBJECTIVE: Following our previous report on acute exacerbation of chronic hepatitis B in breast cancer patients receiving anthracyline-based adjuvant chemotherapy, updated longitudinal data were analyzed focusing on therapeutic and pre-emptive use of lamivudine.
METHODS: Records of 3259 patients at Asan Medical Center between August 2001 and November 2009 were reviewed. The alanine aminotransferase level was graded by Common Terminology Criteria for Adverse Events version 3.0. Hepatitis B virus reactivation was defined as a ≥10-fold increase in hepatitis B virus DNA level compared with baseline or an absolute increase of >10(5) copies/ml. Acute exacerbation or hepatitis flare-up was defined as an increase of serum alanine aminotransferase level to three or more times the upper limit of normal.
RESULTS: In 169 patients showing positive hepatitis B surface antigen, preemptive lamivudine prophylaxis was administered to 41 patients. Overall, 18 (14.1%) of 128 patients without prophylaxis and 2 (4.9%) of 41 patients with prophylaxis showed acute exacerbation during adjuvant chemotherapy (P= 0.164). Toxic or unknown origin hepatitis occurred in 18 (14.1%) of 128 patients without prophylaxis and 1 (2.4%) of 41 patients with prophylaxis (P= 0.046). Treatment interruption occurred in 26 (19.6%) patients without prophylaxis and in 2 (4.8%) patients with prophylaxis (P= 0.062). Age (≥55) was the associated factor for acute exacerbation of chronic hepatitis B (P= 0.040), and the ultrasonographic findings showed the association in subgroup analysis (P= 0.032).
CONCLUSIONS: Pre-emptive use of lamivudine seems to reduce the degree of alanine aminotransferase abnormality and the incidence of hepatitis flare-up. Age (≥55) at initiation of adjuvant chemotherapy was an independently associated factor.