[Clinical outcome in cases of viral breakthrough during lamivudine therapy in chronic hepatitis B patients].
OBJECTIVE
Long-term lamivudine therapy can induce the emergence of lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the mutant is expressed by the reappearance of disappeared HBV DNA in serum. Continued lamivudine treatment has been usually recommended in cases of viral breakthrough. However, the clinical outcome in patients with viral breakthrough is not clear. The aim of this study was to investigate the clinical course of chronic hepatitis B patients after viral breakthrough during lamivudine therapy.


METHODS
A total of 74 patients with chronic hepatitis B who showed viral breakthrough after at least 6 months of lamivudine treatment were included in this study. They had positive HBeAg and HBV DNA before treatment. The median follow-up duration after breakthrough was 13 months.


RESULTS
After viral breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of hepatitis (ALT increase over five-times upper normal limit). These acute exacerbations occurred within three months after breakthrough in 19 patients (63%). In the cases of acute exacerbation, 6 patients showed decompensated progression such as elevation of serum total bilirubin. One of them died of hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg seroconversion occurred in 8 patients after viral breakthrough but their clinical course was highly variable.


CONCLUSIONS
Chronic hepatitis B patients who had viral breakthrough during lamivudine therapy should be followed carefully and regularly in mind of potential clinical deterioration. New strategies are needed to manage the cases of acute exacerbation after viral breakthrough.
Ahn
Soo Hyun
SH
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Chang
Yun Jung
YJ
Oh
Seong Nam
SN
Choi
Do Won
DW
Baek
Soo Jung
SJ
Jeong
Won Seok
WS
Choi
Chang Won
CW
Kim
Kyoung Oh
KO
Yim
Hyung Joon
HJ
Jo
Nam Young
NY
Bak
Jong Jae
JJ
Kim
Jae Seon
JS
Bak
Young-Tae
YT
Lee
Myung Seok
MS
Yeon
Jong Eun
JE
Byun
Kwan Soo
KS
Lee
Chang Hong
CH
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000254:growth & development; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D019259:Lamivudine