- Email: [email protected]
[494] EARLY HBV-DNA SUPPRESSION DURING TREATMENT WITH LAMIVUDINE FOR HBeAg NEGATIVE CHRONIC HEPATITIS B LEADS TO MAINTENANCE OF RESPONSE UNDER TREATMENT
POSTERS
s1xx
Methods: Twenty-two telbivudine-treated patients with VB (confirmed increase in HBV DNA of > I l o g l o copies/mL from nadir) received adefovir in the GLOBE trial, initiated either as follow-on monotherapy (n = 17) or in combination with telbivudine ( n = 5). Patient responses were assessed by clinical and laboratory safety monitoring as well as serum HBV markers, including HBV DNA levels by COBASTMAmplicor assay (LLOD <300 copiesiml). Resistance mutations associated with VB were assessed in PCR-amplified HBV gene sequences by automated DNA sequencing. Results: To date, 21/22 patients had received 2 1 6 weeks of adefovir salvage treatment. With 16 weeks of adefovir, HBV DNA levels decreased by a mean of 4.1 l o g l o copiesiml, and ALT levels were reduced by 93.1 TU/L (Table). HBVDNA levels decreased by a mean of 5.1 l o g l o copies/mL in the subset o f 5 patients who received adefovir in combination with telbivudine, compared to 3.81og10 copies/mL in those 16 patients switched to adefovir monotherapy. All 21 patients had M2041-mutant HBV strains. Consistent with observations of increased risk for resistance with persisting viremia after 6 months, 11/22 (50%) patients with VB had HBV DNA >4 log at Week 24 (vs 8% of patients without VB). Study treatment, including adefovir, continued to be generally welltolerated; there were no serious adverse events reported.
Mcasurcrncnt timc point 1. Baseline value 2. Nadir value on telbivudine monotherapy 3. Valuc at initiation on of adcfovir salwgc Tx Change in value following 16 weeks salvage Tx (all
HBV DNA (loglrr copicslml) Mcdn5SD
ALT (run) Mcan5SD
10.052.5 3.551.0 8.Y52. I -4.151.8*
105.9536.3 56.5531.8 144.05 172.4 -93.151x1.3**
-5.151.5*
-103.85Y4.6**
patients) Changc in vdluc following 16 wccks in subsct ofpaticnts (i’5) = receiving adefovir + telbivudine combination
*p <0.001 for HBVDNA reduction at 16 weeks vs timepoint 3. **p=O.O3 for ALT reduction at I6 wccks 17s timcpoint 3.
Conclusions: Adefovir salvage therapy, as follow-on monotherapy or in combination with telbivudine, resulted in consistent viral suppression for telbivudine-treated patients experiencing virologic breakthrough
14941 EARLY HBV-DNA SUPPRESSION DURING TREATMENT WITH LAMIVUDINE FOR HBeAg NEGATIVE CHRONIC HEPATITIS B LEADS TO MAINTENANCE OF RESPONSE UNDER TREATMENT A S . Hadziyannis’ , S.J. Hadziyannis’,’. ‘Hepatitix Rexearch Luh ut Eugenidion Hospital, Uniuer~xihiof Athens Medicul School; 2Depurtment of’ Medicine, Henry Dunant Hospitul, Athens, Greece E-mail: [email protected] Background and Aims: Early potent suppression of HBV replication at week 24 of chronic hepatitis B (CHB) therapy with telbivudine has recently been claimed to predict high rates of efficacy at year 1 and 2. The aim of this study was to investigate whether or not early HBVDNA suppression under lamivudine (LAM) treatment of HBeAg-negative CHB can predict long term maintenance of virologic response without development of HBV resistance. Patients and Methods: Serial HBV-DNA data from patients included in previously reported large series of more than 200 Greek HBeAgCHB patients with long term LAM treatment were analysed. Fifty six had achieved virologic and biochemical responses maintained for 4 to 5 years. Their serum HBVDNA levels at baseline and under therapy were compared to those in equal number of patients from the same series who experienced virologic and biochemical breakthroughs due to development of LAM HBV resistance. HBV-DNA levels were quantified 6 and 12 months after start of therapy using our in-house real time PCR
assay. Samples with negative HBVDNA results or <1,000 copies/ml were retested with the Cobas TaqMan test (sensitivity 50 copiesiml). The HBVDNA results were analysed in relation to the long-term outcome oftherapy. Results: For patients with serum HBVDNA levels suppressed to nondetectability from month 6 of therapy the possibility of long-term maintenance of virologic response for 4 to 5 and more years was 95% while patients with HBV DNA remaining detectable in levels above 1,000 copies at month 6 had 120% chance for long-term maintenance of response. For individuals achieving the end point of non-detectability of HBV DNA by the applied sensitive PCR assays later than month 6 up to month 12 the predictive value for maintenance of response decreased to 48%. Furthermore all patients who had responses sustained after stopping effective long-term LAM therapy had experienced early, profound and maintained suppression in HBV replication. Conclusion: The result of HBV-DNA testing by most sensitive real time PCR assays during the first 6 months of LAM treatment can be very helpful in optimizing efficacy and predicting the long-term outcome of such therapy.
14951 VlROLOGlC RESPONSE AT TREATMENT MONTH 12 MAY PREDICT SUSTAINED ANTIVIRAL EFFICACY IN ADEFOVIR TREATED LAMIVUDINE-RESISTANT CHRONIC HEPATITIS B WS. Han’, J.E. Yeon’, Y.H. Kim’, S.N. Oh’, Y.S. Seo’, H.J. Yim’, W.H. Choe’, S.Y. Kwon’, K.S. Byun’, C.H. Lee’. ‘Depurtment of Internal Medicine, Korea Uniuersity Medical College, Guro Hospital, Seoul; 2Depurtment of Internul Medicine, Konkuk Uniuersih~Medical College, Konkuk University Hospital, Seoul, Sonth Korea E-mail: [email protected] Background: In lamivudine-treated chronic hepatitis B patients (CHB), maximal HBV DNA reduction early in treatment has been associated with better clinical outcome and lower resistance rate. Aim of our study is to define the potential role of virologic response at treatment 12 month in predicting subsequent virologic and clinical outcome in adefovir (ADV) treated LMV-resistant CHB (LAM-R). Methods: 204 LMV-R CHB treated with ADV were included; mean treatment duration was 18 months (range 6-39). Baseline HBVDNA represented as l o g l o copiesiml was 7.4. Serum HBVDNA was quantified by real time PCR. Biochemical and virologic parameters were measured every 2-3 months. Virologic response at 12 month (VR12) was defined as HBVDNA less than 410g after 12 months. Virologic breakthrough (VBT) was defined as HBVDNA elevation more than 1 loglo from nadir. Genotypic mutation to ADV was detected using mass spectrometry-based genotyping assay (RFMP). Results: VR12 occurred in 110 of 204 patients (54%). In comparison with patients between presence and absence of VR12, mean HBV DNA reduction from baseline at treatment month 12 (Tx. 12) and 24 (Tx.24) were 3.8 vs 1.9, and 3.5 vs 2.4 respectively (p=0.001). HBeAg seroconversion rate at Tx.12 and Tx.24 was 32 vs 14% and 40 vs 27% in each group respectively (p 10.05). The genotypic mutation to ADV at Tx.12 and Tx.24 was 0 vs 6.0% and 21 vs 42% respectively (p=0.014). VBT at Tx. 12, Tx.24 was 0 vs 7.0% and 9.0 vs 25% (p =0.002). Factors associated with VR I2 were baseline HBV DNA level, pretreatment ALT, presence or absence of HBeAg. Conclusion: In treating LMV-R CHB with ADV, 50% of patients were failed to achieve VR12. Absence of VR12 is likely to have less potent viral suppression, lower HBeAg seroconversion and frequent genotypic mutation. Add on or switch to other potent antivirals may need in patients failed to have VR12.
s1xx
Methods: Twenty-two telbivudine-treated patients with VB (confirmed increase in HBV DNA of > I l o g l o copies/mL from nadir) received adefovir in the GLOBE trial, initiated either as follow-on monotherapy (n = 17) or in combination with telbivudine ( n = 5). Patient responses were assessed by clinical and laboratory safety monitoring as well as serum HBV markers, including HBV DNA levels by COBASTMAmplicor assay (LLOD <300 copiesiml). Resistance mutations associated with VB were assessed in PCR-amplified HBV gene sequences by automated DNA sequencing. Results: To date, 21/22 patients had received 2 1 6 weeks of adefovir salvage treatment. With 16 weeks of adefovir, HBV DNA levels decreased by a mean of 4.1 l o g l o copiesiml, and ALT levels were reduced by 93.1 TU/L (Table). HBVDNA levels decreased by a mean of 5.1 l o g l o copies/mL in the subset o f 5 patients who received adefovir in combination with telbivudine, compared to 3.81og10 copies/mL in those 16 patients switched to adefovir monotherapy. All 21 patients had M2041-mutant HBV strains. Consistent with observations of increased risk for resistance with persisting viremia after 6 months, 11/22 (50%) patients with VB had HBV DNA >4 log at Week 24 (vs 8% of patients without VB). Study treatment, including adefovir, continued to be generally welltolerated; there were no serious adverse events reported.
Mcasurcrncnt timc point 1. Baseline value 2. Nadir value on telbivudine monotherapy 3. Valuc at initiation on of adcfovir salwgc Tx Change in value following 16 weeks salvage Tx (all
HBV DNA (loglrr copicslml) Mcdn5SD
ALT (run) Mcan5SD
10.052.5 3.551.0 8.Y52. I -4.151.8*
105.9536.3 56.5531.8 144.05 172.4 -93.151x1.3**
-5.151.5*
-103.85Y4.6**
patients) Changc in vdluc following 16 wccks in subsct ofpaticnts (i’5) = receiving adefovir + telbivudine combination
*p <0.001 for HBVDNA reduction at 16 weeks vs timepoint 3. **p=O.O3 for ALT reduction at I6 wccks 17s timcpoint 3.
Conclusions: Adefovir salvage therapy, as follow-on monotherapy or in combination with telbivudine, resulted in consistent viral suppression for telbivudine-treated patients experiencing virologic breakthrough
14941 EARLY HBV-DNA SUPPRESSION DURING TREATMENT WITH LAMIVUDINE FOR HBeAg NEGATIVE CHRONIC HEPATITIS B LEADS TO MAINTENANCE OF RESPONSE UNDER TREATMENT A S . Hadziyannis’ , S.J. Hadziyannis’,’. ‘Hepatitix Rexearch Luh ut Eugenidion Hospital, Uniuer~xihiof Athens Medicul School; 2Depurtment of’ Medicine, Henry Dunant Hospitul, Athens, Greece E-mail: [email protected] Background and Aims: Early potent suppression of HBV replication at week 24 of chronic hepatitis B (CHB) therapy with telbivudine has recently been claimed to predict high rates of efficacy at year 1 and 2. The aim of this study was to investigate whether or not early HBVDNA suppression under lamivudine (LAM) treatment of HBeAg-negative CHB can predict long term maintenance of virologic response without development of HBV resistance. Patients and Methods: Serial HBV-DNA data from patients included in previously reported large series of more than 200 Greek HBeAgCHB patients with long term LAM treatment were analysed. Fifty six had achieved virologic and biochemical responses maintained for 4 to 5 years. Their serum HBVDNA levels at baseline and under therapy were compared to those in equal number of patients from the same series who experienced virologic and biochemical breakthroughs due to development of LAM HBV resistance. HBV-DNA levels were quantified 6 and 12 months after start of therapy using our in-house real time PCR
assay. Samples with negative HBVDNA results or <1,000 copies/ml were retested with the Cobas TaqMan test (sensitivity 50 copiesiml). The HBVDNA results were analysed in relation to the long-term outcome oftherapy. Results: For patients with serum HBVDNA levels suppressed to nondetectability from month 6 of therapy the possibility of long-term maintenance of virologic response for 4 to 5 and more years was 95% while patients with HBV DNA remaining detectable in levels above 1,000 copies at month 6 had 120% chance for long-term maintenance of response. For individuals achieving the end point of non-detectability of HBV DNA by the applied sensitive PCR assays later than month 6 up to month 12 the predictive value for maintenance of response decreased to 48%. Furthermore all patients who had responses sustained after stopping effective long-term LAM therapy had experienced early, profound and maintained suppression in HBV replication. Conclusion: The result of HBV-DNA testing by most sensitive real time PCR assays during the first 6 months of LAM treatment can be very helpful in optimizing efficacy and predicting the long-term outcome of such therapy.
14951 VlROLOGlC RESPONSE AT TREATMENT MONTH 12 MAY PREDICT SUSTAINED ANTIVIRAL EFFICACY IN ADEFOVIR TREATED LAMIVUDINE-RESISTANT CHRONIC HEPATITIS B WS. Han’, J.E. Yeon’, Y.H. Kim’, S.N. Oh’, Y.S. Seo’, H.J. Yim’, W.H. Choe’, S.Y. Kwon’, K.S. Byun’, C.H. Lee’. ‘Depurtment of Internal Medicine, Korea Uniuersity Medical College, Guro Hospital, Seoul; 2Depurtment of Internul Medicine, Konkuk Uniuersih~Medical College, Konkuk University Hospital, Seoul, Sonth Korea E-mail: [email protected] Background: In lamivudine-treated chronic hepatitis B patients (CHB), maximal HBV DNA reduction early in treatment has been associated with better clinical outcome and lower resistance rate. Aim of our study is to define the potential role of virologic response at treatment 12 month in predicting subsequent virologic and clinical outcome in adefovir (ADV) treated LMV-resistant CHB (LAM-R). Methods: 204 LMV-R CHB treated with ADV were included; mean treatment duration was 18 months (range 6-39). Baseline HBVDNA represented as l o g l o copiesiml was 7.4. Serum HBVDNA was quantified by real time PCR. Biochemical and virologic parameters were measured every 2-3 months. Virologic response at 12 month (VR12) was defined as HBVDNA less than 410g after 12 months. Virologic breakthrough (VBT) was defined as HBVDNA elevation more than 1 loglo from nadir. Genotypic mutation to ADV was detected using mass spectrometry-based genotyping assay (RFMP). Results: VR12 occurred in 110 of 204 patients (54%). In comparison with patients between presence and absence of VR12, mean HBV DNA reduction from baseline at treatment month 12 (Tx. 12) and 24 (Tx.24) were 3.8 vs 1.9, and 3.5 vs 2.4 respectively (p=0.001). HBeAg seroconversion rate at Tx.12 and Tx.24 was 32 vs 14% and 40 vs 27% in each group respectively (p 10.05). The genotypic mutation to ADV at Tx.12 and Tx.24 was 0 vs 6.0% and 21 vs 42% respectively (p=0.014). VBT at Tx. 12, Tx.24 was 0 vs 7.0% and 9.0 vs 25% (p =0.002). Factors associated with VR I2 were baseline HBV DNA level, pretreatment ALT, presence or absence of HBeAg. Conclusion: In treating LMV-R CHB with ADV, 50% of patients were failed to achieve VR12. Absence of VR12 is likely to have less potent viral suppression, lower HBeAg seroconversion and frequent genotypic mutation. Add on or switch to other potent antivirals may need in patients failed to have VR12.