Is Lamivudine Efficacious for Chronic Hepatitis B Infection?
Clinical Question
Will lamivudine administration result in reduced transaminase levels and
risk of chronic acitve hepatitis?
Clinical Bottom Line
- Lamivudine, the (-) enantiomer of 3'-thiacytidine, is a potent inhibitor of
viral DNA synthesis and reverse transcriptase activity, and effectively reduced
to undetectable levels measured serum HBV DNA during 12 weeks of therapy.
- The vast majority of patients had reappearance of viral DNA after therapy
was stopped.
The Evidence
|
|
Lamivudine dose |
|
|
|
25 mg (N=10) |
100 mg (N=11) |
300 mg (N=11) |
All Patients (N=32) |
| HBV DNA @ week 12 (pg/ml) |
9 ±4 |
1±0 |
3±2 |
|
| % with suppression |
70 |
100 |
100 |
91 |
| suppression T1/2 |
8 |
4 |
2 |
|
| % with sustained suppression |
0 |
36 |
18 |
19 |
| % with elevation of ALT |
|
|
|
|
| >2-fold |
50 |
36 |
36 |
41 |
| >3-fold |
10 |
18 |
18 |
16 |
- The majority of patients in all treatment groups had return of detectable
levels of HBV DNA after stopping therapy.
- No significant reductions in ALT were noted; to the contrary, significant
percentages increased, although less so in the 100 and 300 mg groups.
Comments
- This was a randomized trial.
- There was no control group.
- No significant statistical analyses were performed on any of the clinically
important outcomes (which essentially were not addressed). However, the primary
outcome of interest was in reduction in serum levels of HBV DNA, and this was
noted for all dose groups to be statistically significant.
- The results are valid according to the JAMA guidelines for therapy,
however, there is insufficient statistical power to recommend
this therapy for patients with chronic Hepatitis B infection at this time.
- It would be sound to wait for larger, controlled, and statistically
rigorous studies to be published before determining the clinical usefulness of
this drug. Other important outcomes need to be addressed, i.e., death,
cirrhosis, hepatocellular carcinoma, etc.
APPRAISED BY: Woraphot Tantisiriwat, MD, MPH
DATE: January 31, 1996
Dienstag DL, et al. A Preliminary Trial of Lamivudine for Chronic
Hepatitis B Infection. NEJM 1995;333:1657-1661.
