| Entecavir is Associated with Improved Liver Histology and Reduced HBV DNA in Patients with Lamivudine-Resistant Virus
Treatment of hepatitis B virus (HBV) that has developed resistance to lamivudine (Epivir-HBV) remains a challenging aspect of hepatitis B therapy. In this prospective, randomized, controlled trial, patients with lamivudine-refractory HBeAg-positive chronic HBV infection were randomly assigned to either receive the investigational nucleoside analogue entecavir (Baraclude) or else remain on lamivudine for at least 48 weeks.
All patients were analyzed according to whether they experienced histological improvement or achieved HBV DNA < 300 copies/mL. Histological improvement was defined as at least a 2-point decrease in Knodell necroinflammatory score with no worsening of fibrosis (defined as a 1-point or greater increase in Knodell fibrosis score).
The relationship between efficacy and baseline disease and demographic characteristics was assessed. Disease-related variables included baseline alanine aminotransferase (ALT), HBV DNA, and HBV genotype. Demographic variables included geographic region, age, sex, and race.
Results
- After 48 weeks, patients who received entecavir experienced a mean HBV DNA reduction of 5.11 log10 copies/mL, compared with a reduction of 0.48 log10 copies/mL among patients receiving lamivudine.
- About twice as many patients taking entecavir experience histological improvement compared with those taking lamivudine (55% vs 28%, respectively).
- No relationship was observed between baseline disease-related or demographic characteristics and virological or histological response to entecavir (see table).
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Histologic Improvement
at Week 48 |
HBV DNA < 300 copies/mL
at Week 48 |
Baseline Variable |
ETV n (%)
N=124 |
LVD n (%)
N=116 |
ETV n (%)
N=141 |
LVD n (%)
N=145 |
HBV Genotype
A
B
C
D |
18/33 (55)
14/21 (67)
14/26 (54)
17/35 (49) |
7/28 (25)
6/16 (38)
2/26 (8)
16/37 (43) |
12/37 (32)
6/23 (26)
5/27 (19)
3/45 (7) |
0/32 (0)
1/17 (6)
0/28 (0)
1/56 (2) |
ALT
<2 x ULN
2–5 x ULN
>5 x ULN |
27/58 (47)
28/59 (57)
13/17 (76) |
17/59 (29)
12/43 (28)
3/14 (21) |
8/66 (12)
13/55 (24)
6/20 (30) |
0/76 (0)
0/53 (0)
2/16 (13) |
HBV DNA
<107 c/mL
107-<108 c/mL
108-<109 c/mL
109-<1010 c/mL
≥1010 c/mL |
8/11 (73)
4/11 (36)
17/29 (59)
22/44 (50)
17/29 (59) |
5/9 (56)
2/9 (22)
10/33 (30)
13/47 (28)
2/18 (11) |
9/22 (41)‡
5/33 (15)
6/52 (12)
7/34 (21) |
0/25(0)‡
0/37 (0)
1/57 (2)
1/26 (4) |
‡<108 copies/mL HBV DNA |
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ETV=entecavir; LVD=lamivudine; ULN=upper limit of normal |
Conclusion
The researchers concluded that patients with lamivudine-resistant HBV were significantly more likely to exhibit virological (HBV DNA < 300 copies/mL) and histological improvement when they switched to entecavir as opposed to remaining on lamivudine. Such improvement occurred regardless of baseline demographic characteristics, baseline serum ALT, baseline HBV DNA, or HBV genotype.
5/30/06
Reference
ML Shiffman, Z Goodman, PJ Paul, and others.Entecavir (ETV) is Associated with an Improvement in Liver Histology and a Reduction in HBV DNA in Patients with Lamivudine-Refractory HBeAg(+) Regardless of Baseline Characteristics. Abstract T1845. DDW 2006. May 20-25, 2006. Los Angeles, CA.
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