Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
BACKGROUND
The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown.


METHODS
Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine aminotransferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls.


RESULTS
Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for > or =6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment (P=0.02).


CONCLUSIONS
Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine.
Wong
Vincent Wai-Sun
VW
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR.
Wong
Grace Lai-Hung
GL
Tsang
Steven Woon-Choy
SW
Hui
Alex Yui
AY
Chim
Angel Mei-Ling
AM
Yiu
Karen Kar-Lum
KK
Chan
Hoi-Yun
HY
Chan
Francis Ka-Leung
FK
Sung
Joseph Jao-Yiu
JJ
Chan
Henry Lik-Yuen
HL
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine