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Abstract
Background/Aims
Clevudine is a potent antiviral agent that has demonstrated efficacy in patients with chronic hepatitis B. This study compared the efficacy of clevudine (C), entecavir (E) and lamivudine (L) in treatment-naive patient with HBeAg-positive chronic hepatitis B.
Methods
A total of 146 treatment-naive patients with HBeAg-positive chronic hepatitis B received clevudine, entecavir or lamivudine. C group (n=39) received 30 mg of clevudine, E group (n=39) received 0.5 mg of entecavir and L group (n=68) received 100 mg of lamivudine once a day for more than 48 weeks. The efficacy analysis estimated the mean changes of the HBV DNA levels as a virologic response, the normalization of the ALT levels (less than 35 IU/L) as a biochemical response and loss of HBeAg or seroconversion as a serologic response. The serum HBV DNA level was quanti-fied by hybrid capture and real-time PCR assay.
Results
Before the administration of clevudine, entecavir and lamivudine, the mean HBV DNA and ALT levels and the gender and age were well balanced among the three groups (p＞0.05). For the virologic response at 48 weeks, the mean changes of the HBV DNA levels from baseline of the C, E and L groups were −3.8±2.2, −4.5±1.9 and −2.5±2.1 log copies/mL. C and E group showed superior antiviral activity compared to that of L group (p＜0.0001), but no significant differences in antiviral response were noted between C and E groups. For the biochemical response at 48 weeks, the normalization of the ALT levels (less than 35 IU/L) among the C, E and L groups was 82%, 74% and 71%, respectively (p=0.46). The rates of undetectable serum HBV DNA (less than 300 copies/mL) of the C, E and L groups were 39%, 69% and 27%, respectively (p＜0.0001). For the serologic response at 48 weeks, the loss of HBeAg was 13%, 31% and 24% and the seroconversion was 10%, 23% and 17%, respectively. There was no difference of efficacy among the three groups regarding ALT normalization or serologic response (p＞0.05). Viral breakthrough in C group was noted at 24 weeks (5%) and 48 weeks (21%), but no biochemical breakthrough was noted. The elevation of the serum CK level was noted in only 1 patient of group C at 48 weeks (2.56%) after therapy. For the patients without or with liver cirrhosis (LC), C and E group showed superior antiviral activity compared to that of the L group, but the antiviral activity was more effective in non- LC group than LC group (p＜0.0001 vs p=0.036).
Conclusions
Clevudine therapy compared with lamivudine for 48 weeks showed significantly potent antiviral efficacy in treatment-naive patients with HBeAg-positive chronic hepatitis B, and especially in the non-LC patients. However, the antiviral efficacy of clevudine was similar to that of entecavir even though taking into account relatively short follow up period and retrospective study.
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Fig. 1.
Schema of study population though 48 weeks. HCC, hepatocelluar carcinoma; LC, liver cirrhosis.
Fig. 2.
Changes of HBV DNA level (log copies/mL) from baseline through the 48 weeks. Mean±95% confidence interval plot of HBV DNA level (log copies/mL) according to PCR through 48 weeks by groups treated with clevudine, entecavir and lamivudine. p-values were derived from ANOVA for the comparison of change from baseline by groups.
Fig. 3.
Changes of serum ALT level (IU/L) from baseline through the 48 weeks. Mean±95% confidence interval plot of serum ALT level (IU/L) through 48 weeks by groups treated with clevudine, entecavir and lamivudine. p-values were derived from ANOVA for the comparison of change from baseline by groups.
Table 1.
Baseline Characteristics of the Patients
Table 2.
Changes of HBV DNA Level (log copies/mL) from Baseline
| HBV DNA (log copies/mL) | Clevudine (n=39) | Entecavir (n=39) | Lamivudine (n=68) | p-value |
|---|---|---|---|---|
| At baseline | 7.0±1.5 | 6.9±1.4 | 7.3±1.3 | 0.34 |
| Change from baseline | ||||
| 12 weeks | −3.7±1.2∗ | −3.5±1.7∗ | −2.3±1.5† | ＜.0001 |
| 24 weeks | −4.3±1.5∗ | −4.3±1.5∗ | −2.7±1.6† | ＜.0001 |
| 36 weeks | −4.2±1.6∗ | −4.5±1.4∗ | −2.6±2.1† | ＜.0001 |
| 48 weeks | −3.8±2.2∗ | −4.5±1.9∗ | −2.5±2.1† | ＜.0001 |
Table 3.
Changes of Serum ALT Level (IU/L) from Baseline
Table 4.
Virologic, Biochemical, and Serologic Response at 48 Weeks
| Variable | Clevudine (n=39) | Entecavir (n=39) | Lamivudine (n=68) | p-value |
|---|---|---|---|---|
| HBV DNA ＜300 (copies/mL) (%) | 14 (39)∗ | 20 (69)† | 18 (27)∗ | ＜.0001‡ |
| ALT ＜35 (IU/L) | 32 (82) | 28 (74) | 48 (71) | 0.46 |
| Loss of HBeAg | 5 (13) | 12 (31) | 16 (24) | 0.15 |
| Seroconversion | 4 (10) | 9 (23) | 11 (17) | 0.32 |
Table 5.
Changes of HBV DNA (log copies/mL) from Baseline
| HBV DNA (log copies/mL) | Non-LC | LC | ||||||
|---|---|---|---|---|---|---|---|---|
| Clevudine (n=21) | Entecavir (n=22) | Lamivudine (n=35) | p-value | Clevudine (n=18) | Entecavir (n=17) | Lamivudine (n=33) | p-value | |
| At baseline | 8.0±1.2∗ | 7.0±1.6† | 7.8±1.1∗† | 0.042 | 5.9±1.2 | 6.7±1.1 | 6.8±1.3 | 0.058 |
| Change from baseline | ||||||||
| 12 weeks | −4.3±1.0∗ | −3.7±2.0∗ | −2.5±1.7† | 0.0010 | −3.1±1.0∗ | −3.3±1.1∗ | −2.0±1.3† | 0.0013 |
| 24 weeks | −5.0±1.1∗ | −4.5±1.5∗ | −2.9±1.6† | ＜0.0001 | −3.4±1.4∗ | −3.9±1.4∗ | −2.6±1.6† | 0.015 |
| 36 weeks | −5.0±1.1∗ | −4.8±1.4∗ | −2.7±2.3† | ＜0.0001 | −3.2±1.6 | −4.0±1.4 | −2.6±1.9 | 0.070 |
| 48 weeks | −4.±1.2∗ | −4.8±2.3∗ | −2.5±2.2† | ＜0.0001 | −2.5±2.6∗ | −4.2±1.2∗ | −2.5±2.0† | 0.036 |
Table 6.
Changes of Serum ALT (IU/L) from Baseline
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