| Marked ALT Flares During Therapy with Peginterferon Alfa-2a, Lamivudine or the Two Drugs Combined May Be Beneficial in Patients with HBeAg-negative Chronic HBV
Prominent ALT flares occurring during, or shortly after, interferon-based treatment of HBeAg-positive chronic hepatitis B (CHB) have been associated with HBeAg seroconversion and increased viral suppression. The relationship between ALT flares and response in patients with HBeAg-negative CHB has not been defined.
The objective of the current study was to investigate the relationship between ALT flares and response in a randomized, partially double-blind, multinational study of peginterferon alfa-2a (40KD) (PEGASYS) with and without lamivudine vs lamivudine alone in 537 patients with HBeAg-negative CHB.
Patients with HBeAg-negative CHB received one of the following: peginterferon alfa-2a (40KD) (PEGASYS?/sup>), 180 μg once weekly (qw) + placebo once daily (qd); peginterferon alfa-2a (40KD) (PEGASYS?/sup>), 180 μg qw + lamivudine 100 mg qd; or lamivudine 100 mg qd.
Patients were treated for 48 weeks with 24 weeks treatment-free follow-up. Co-primary endpoints were (1) ALT normalization, and (2) HBV DNA <20,000 copies/ml, assessed after 24 weeks follow-up (week 72).
For this analysis, marked ALT flares were a peak ALT >10 x the upper limit of normal (ULN) and moderate ALT flares were a peak ALT between 5 and 10 x ULN.
Results
The incidence of marked on-therapy ALT flares was significantly higher with peginterferon alfa-2a monotherapy than with combination therapy or lamivudine monotherapy (P=0.007 and P=0.038, respectively).
During follow-up, marked flares were significantly more frequent with lamivudine monotherapy or combination therapy than peginterferon alfa-2a monotherapy (P=0.033 and P=0.021, respectively).
A similar trend was observed with moderate ALT flares during follow-up (see table). Overall, there was a significant association between marked on-therapy ALT flares and ALT normalization at week 72 (P=0.011), but not between moderate flares and ALT normalization at week 72.
Conclusions
In conclusion, the authors write, 揗arked on-therapy ALT flares occurred more frequently in patients who achieved a sustained response. This suggests that a marked flare during therapy with peginterferon alfa-2a (40KD) (PEGASYS?/sup>), lamivudine or the two agents combined may be beneficial in patients with HBeAg-negative CHB.?/span>
? It is noteworthy that, although this relationship has previously been observed in HBeAg-positive CHB, these data represent the first report of such a relationship in patients with HBeAg-negative CHB.?/span>
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发表于 2004-11-11 20:24
