治疗中/后ALT上升几率恩替较拉米低(2005.5 DDW)

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Alanine Aminotransferase Flares (ALT) Are Less Frequent with Entecavir Than Lamivudine Treatment Both On- and Off-treatment in HBeAg(+) Patients

Entecavir/ ETV (Baraclude) is a potent, selective inhibitor of HBV DNA polymerase. Alanine aminotransferase (ALT) flares may be a consequence of host immune function or enhanced HBV replication and may occur on- or post-treatment in patients with chronic hepatitis B. An anti-HBV agent that suppresses HBV replication may influence the incidence of ALT flares.

ALT elevations were analyzed in two Phase 3 trials in HBeAg(+) patients. ETV-022 randomized 709 nucleoside-na飗e patients to ETV 0.5mg QD or lamivudine/LVD (Epivir-HBV) 100mg QD for up to 96 weeks.?

ETV-026 randomized 286 LVD-refractory patients to ETV 1.0mg QD or continued LVD 100mg QD for up to 96 weeks.

For both studies, patients with HBV DNA < 0.7 MEq/mL and HBeAg loss at 48 weeks discontinued treatment and were followed 24 weeks off-treatment. ALT flares on-treatment were defined as ALT > 2 x baseline and > 10 x ULN.

Results

?span style='font:7.0pt "Times New Roman"'> On-treatment ALT flares were observed for 12 (3%) ETV and 23 (6%) LVD patients in ETV-022, and in 1 ETV (<1%) and 16 (11%) LVD patients in ETV-026.

?span style='font:7.0pt "Times New Roman"'> 牋All ETV flares were associated with a >2 log10 reduction in HBVDNA that preceded or coincided with ALT elevation and was maintained for the treatment period, with 12/13 flares resolving on-treatment.

?span style='font:7.0pt "Times New Roman"'> One subject discontinued ETV due to ALT flare (HBV DNA remained undetectable by PCR).

?span style='font:7.0pt "Times New Roman"'> All 16 flares on LVD in ETV-026 and 12/23 (52 %) in ETV-022 were associated with increasing or unchanged HBV DNA that preceded or coincided with ALT elevation.

?span style='font:7.0pt "Times New Roman"'> Eight patients discontinued LVD due to flare.

?span style='font:7.0pt "Times New Roman"'> Among ETV-022 patients with on-treatment flares, 1/12 ETV and 5/23 LVD patients experienced a clinical or laboratory abnormality consistent with hepatic dysfunction, and one LVD patient died of hepatic failure.

?span style='font:7.0pt "Times New Roman"'> ALT flares during off-treatment follow-up were observed in 3 (2 %) ETV and 9 (6 %) LVD patients and in 9/12 cases were associated with a return of serum HBV DNA toward baseline levels.

?span style='font:7.0pt "Times New Roman"'> No off-treatment ETV flares resulted in hepatic decompensation.

Conclusion

The authors conclude, 揂LT flares on ETV therapy are uncommon and generally associated with declines in serum HBV DNA and a benign clinical course. ALT flares on LVD are frequently associated with loss of therapeutic effect.?/span>

05/18/05

Reference N Tsai and others. Alanine Aminotransferase (ALT) Flares Are Less Frequent With Entecavir Than Lamivudine Treatment Both On- and Off-Treatment in HBeAg(+) Patients. Abstract M942. Digestive Disease Week 2005. May 14-18, 2005. Chicago, IL.