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interferon-α combination therapy in chronic hepatitis B patients
HEPATOLOGYVoL 34, No. 4, Pt. 2, 2 0 0 1
AASLD ABSTRACTS
631A
1835
1836
IMMLrNOGEN1CITY OF HEPATITIS B VACCINATION IN CHILD'S CLASS A O R B PATIENTS W I T H A L C O H O L I C CIRRHOSIS, Manuel Ro~ driguez, Luisa G Dieguez, Monica G Espiga, Mercedes Rodriguez, Rosario F Velazquez, Arancha Alvarez, Luis Rodrigo, Hospital Central de Asturias, Oviedo Spain
VIRAL KINETICS IN HBEAG POSITIVE A N D NEGATIVE PATIENTS W I T H HBV-RELATED CIRRItOSIS TREATED LONG-TERM W I T H LAMIVUDINE. Pietro Lampertico, Mauro Vigano', Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy; Giovanna Lunghi, Anna Orlandi, Laboratory of Virology, IRCCS Maggiore Hospital, Milan Italy; Raffaella Romeo, Massimo A Iavarone, Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy; Ginseppe Colucci, Roche Molecular Systems, Rotkreuz Switzerland; Ersilio Del Ninno, Massimo Colombo, Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy
BACKGROUND: The i m m u n o g e n i c i t y of HBV vaccination in patients waiting for or after liver transplantation is in general low. However, little is k n o w n about the reactivity of the vaccine in patients with liver cirrhosis in an earlier stage. AIMS: To asses the response rate to hepatitis B vaccination in patients with alcoholic cirrhosis w h o were in C h i l d - P u g h ' s class A or B a n d to identify potential factors interfering with an adequate response. PATIENTS AND METHODS: 94 patients with alcoholic cirrhosis (72 Child's A a n d 22 Child's B class) a n d negative for HBsAg, antiHBc, antiHBs a n d antiHCV in s e r u m were w~ccinated with double dosis (40/xg) of r e c o m b i n a n t vaccine intramuscularly at 0, 1 a n d 6 months. AntiHBs s e r u m levels were determined one m o n t h after the last dosis in all patients a n d subsequently every 6 m o n t h s in responders. Response was considered w h e n antiHBs was -- 10 mIU/ml a n d high-response w h e n it was -> 100 mlU/ml. The effect on the response of 20 clinical a n d biological variables recorded before or d u r i n g vaccination was assessed. Statistical analysis was p e r f o r m e d using Chi-squared a n d s t u d e n t ' s t test a n d the Kaplan-Meier method. RESULTS: Response was obtained in 57/94 (61%) patients (geometric m e a n titer of antiHBs: 2 9 1 2 3 2 9 ) . A m o n g the 20 variables analysed, only a baseline s e r u m albumin -~ 4.3 g/dl (response rate 55% vs. 92%; p = 0 . 0 1 ) was associated with primary n o n r e s p o n s e A high-response was elicited in 34 out of 57 (60%) responders. A m o n g responders, patients with 5 points in the Child-Pugh score achivied higher antiHBs leveIs ( 3 4 9 2 3 6 7 mIU/ ml) than those with more than 5 points (120 2 198 mlU/ml) ( p = 0.002). The cumulative probability to maintain antiHBs levels >-- 10 mlU/ml at 6, 12 a n d 18 m o n t h s after the last dosis was higher in patients with highresponse (100%~ 89% and 76%) than in those with lowresponse (60%, 30% a n d 15%) (p =0.00001). CONCLUSIONS: The rate a n d intensity of response to vaccination against HBV in patients with alcoholic cirrhosis in ChiId's class A or B depend on the grade of liver disfunction. Like in other groups, persistence of antibody is related to the maximal level of antiHBs achived after vaccination. Patients w h o elicit a lowresponse could obtain benefit from booster dosis of vaccine.
Background and Aim. Patients treated long-term with lamivudine are at high risk of developing YMDD mutants, but predictors of virological breakthrough are still poorly defined. Aim of the study was to assess the kinetics of HBV-DNAduring therapy and correlate these findings with antiviraI response and development of YMDD mutants. Patientsand Methods. 50 patients (44 men, 49 yr, 34 HBeAgnegative, 39 cirrhotics) with chronic hepatitis B were treated with lamivudine 100 or 150 rag/daily for 9-51 months (median 30). Patients were checked every two months with liver function tests, HBV-DNAby nou-PCR assays (Digene or bDNA, >1x106 copies/ml), and by quantitative PCR (Amplicor HBV Monitor, Roche, ;>4x102 eopies/ml), and IgM anti-HBc (MEIA, Abbott). YMDD mutants were looked for by direct sequencing using an automated Sequencer (Pharmacia) in patients with a virological breakthrough, defined as reappearance of serum HBV-DNAby non-PCR assays in a patient who initially responded to therapy. Results. At baseline, ALT were 134 IU/L (31-1900), HBV-DNA9x106 copies/ml (3x104->4x107) by quantitative PCR, IgM anti-HBc 0.71 index (0.08~3.35). After 6 months of therapy, 48 (96%) patients had normal ALT levels and 50 (100%) had undetectable HBV-DNA by non-PCR assays. 37 patients maintained normal ALT leveIs and undetectable HBV-DNAby non-PCR assays throughout the study, whereas 13 (26%) developed YMDD mutants between month 8 and 21 (median 13). Serum HBVDNA by quantitative PCR fell below 103 copies/ml in 23 (68%), 29 (86%), and 31 (91%) HBeAg negative patients by month 2, 4 and 6, respectively. The corresponding features for HBeAg positive patients were 1 (6%), 4 (25%) and 6 (37%) (p<0.001). Overall, 9 of 13 (69%) patients with HBV-DNA >103 copies/mI at month 6 developed mutants in the following 18 months of therapy as compared to 4 of 37 (l 1%) patients with < 103 copies/ml (p<0.001). Seroconversion to anti-HBe occurred in 5 of 6 HBeAg positive patients with HBV-DNA < 103 copies/ml at month 6 as compared to 3 of l0 patients with > 103 copies/mI of HBV-DNA. In 10 of 13 patients with YMDD mutants, HBV-DNA by quantitative PCR significantlyincreased to 104-105copies/ml in the 2-6 months prior to the reappearance of HBV-DNAby Digene or bDNA assays. The 37 patients who showed normal ALT levels and undetectable HBV-DNAby Digene or bDNA throughout the 24 months of study, were also tested by quantitative PCR; HBV-DNA remained persistently ondeteetable (<400 copies/ ml) in 13 patients (35%), whereas 103-104copies/ml of HBV-DNAwere identified in at least one serum sample in 24 cases (65%). Conclusions: HBV suppression by lamivudine occurs earlier in HBeAg negative than in HBeAg positive patients. YMDD mutants occur more frequently in patients with > l03 copies/ml HBV-DNA at month 6. Low-level HBV replication is transiently detected by quantitative PCR in many patients without YIVIDDmutants.
18,37
1838
THE RESULTS OF LAMIVUDINE/INTERFERON-ct COMBINATION THERAPY IN CHRONIC HEPATITIS B PATIENTS. Can P Eyigun, A y h a n Kubar, Ali Sengul, Bulent Celasun, Ufuk Dizer, Alaaddin Pahsa, Gulhane Military Medical Academy, Ankara Turkey
INTERFERON ALFA A N D FAMCICLOVIR FOR CHRONIC HBSAG A N D ANTI-HBE POSITIVE PATIENTS - AN INTERIM ANALYSIS. Reel E Sentjens, Marcel Beld, Sjoerd Rebers, Henk W Reesink, AMC, Amsterdam Netherlands
Lamivudine (LAM) and Interferon-o~, (IFN-o0 are effective in inhibiting Hepatitis B Virus (HBV) replication in chronic hepatitis B patients (CHBPs) and used each alone or in combination to treat CHBPs. Aim: To evaluate the efficacy of combination therapy. Methods: Twenty-one CHBPs with eAg+(18M/3F, mean age 30-+6 yrs)(Group AI) and 2I with eAg-(19M/2F, mean age 3I-+6.1 yrs) (Group A2) were treated with 4-.5 or 5 MU 1FN-o:/d and IAM 100mg/d for 9 months in combination and plus 3 months with LAM 100mg/d alone. Twenty-eight CHBPs with eAg+ (24M/4F, mean age 28-+7.lyrs) (Group B1) and 27 with eAg- (27M, mean age 38-+9)(Group 82) were treated with 4.5 or 5 MU IFN-odd and LAM 100mg/d for 9 months in combination and LAM 100mg/d is being still given (mean duration 19.1±6.9 months). The necroinfiammatory activity and fibrosis were evaluated according to modified Knodell scoring system within six months before therapy and six months after IFN-a was stopped. HBV-DNA was assessed by PCR (In house and Cobas amplicor system, Roche, Switzerland). HBsAg, HBeAg and anti-HBe were assessed by EIA (Murex, Abbot Lab.,IL,USA). Results: HBV-DNA was negative in all 4 groups by PCR at the end of IFN-o~ therapy and then became positive in 17 (80.9%)in Group A1,7 (33.3%) in Group A2 and none in group B six months after IFN-o~ was stopped.But virological berakthrough occurred in 3 pts in Gr.B1 and 2 in Gr.B2 at average 23.4-+6.5 months.HBeAg/anti-HBeAgseroconversion was seen in 7 (33.3%)pts, in 15 (53.6%)at the end of 1FN-a therapy in Gr.A1 and Gr.Bl,respectively. In Gr.A1, HBeAg/anti-HBe seroconversion was also found in extra 4 pts while HBeAg was becoming positive in 2 pts six months after IFN-a ended. Improvement in HAI and fibrosis scores was also noted in all groups. Conclusions: 1.LAMAFN-oe combination therapy was found to be effective in treatment of CHBPs.2. LAMBFN-a combination therapy seemed to prevent YMDD mutations.3. LAM should be continued after IFN-oe was stopped.
Objectives: To establish if combination therapy with interferon c~-2a (IFN) and Famciclovir can provoke disappearance of HBsAg a n d HBV DNA. Methods: Twelve treatment-naive chronic HBsAg a n d anti-HBe positive hepatitis B patients received IFN 9 MU t.i.w, combined with Famiclovir 3x500 mg daily for 24 weeks. Serum samples were obtained at week O, 8 a n d 24 during treatment a n d 6 m o n t h s after stopping treatment. HBV DNA levels were determined using the Quantiplex HBV 1.0 bDNA assay (Bayer, detection limit 7x10 s copies/ml). W h e n results were below the detection limit of the bDNA, HBV DNA was measured by qualitative PCR (Roche HBV m o n i t o r 2.0 assay, detection limit 4 x l 0 1 copies/ml). Results: Ten male a n d 2 female patient were studied. All patients were HBsAg positive, HBeAg negative, anti-HBe positive a n d HBVDNA positive as measured by PCR. Mean pretreatment ALAT values were 146 U/L (range 10-800) (upper limit of normal 45 U/L). Mean pretreatment viral load was 5.6 log eopies/ml. The viral load decline after 8 weeks was 2.1 log copies/ml. F r o m week 8 to 24, 5 patients h a d a m e a n viral load increase of 0.5 log, 3 patients h a d a mean viral load decrease of 0.9 log, a n d 4 patients had no change in viral load. During the follow up period 11 patients h a d an increase of viral load of 1.6 log copies/ml the m e a n viral load at the end of follow u p was 4.8 log copies/ml. At the end of treatment 6/12 patients were HBV-DNA negative as measured b y PCR. One of 12 patients remained HBV-DNA negative at the end of the follow up. None of the patients became HBsAg negative at airy time period. Mean ALAT value at 8 weeks of treatment was 70 U/L (range 16-231) and the m e a n ALAT values at the end of treatment a n d at the end of follow up were 94 U/L (range 15-481) a n d 72 U/L (t 1-263) respectively. 5/12 patients h a d normal ALAT values at the end of follow up. Conclusions: A combination therapy of IFN a n d Famciclovir induced in none of the patients disappearance of HBsAg. During therapy HBV DNA levels d r o p p e d but returned to approximately pretreatment levels 6 m o n t h s after stopping therapy.
Table 1. Cllemical Responses of Treated Patients with Hepatitis B
At A2 81 82
Mean Mean Mean Mean AST%SD AST%SO AS'I'3-+SD A L T % S D
Mean Mean A L T % S D ALT3_+SD
91.9±61.6 6&7_+4&l 72±3&1 59.8_+29,2
42,6_+24.7 47±31,5 43.8±22 4&2_+21.1
35.7_15,2 37+_16,1 37,4±14,9 39_+24,5
43,2~2&8 42,3~49,3 26,7_+12.3 24,2_+4.54
168.+,+128 124.3±t17.9 I46,6±100,t 129_+83
1: Baseline 2; At the end of IFN-~ therapy 3: Six months after IFN-ct Therapy
69,5_+64 62±95,8 27_.+25.9 29_+10.8
AASLD ABSTRACTS
631A
1835
1836
IMMLrNOGEN1CITY OF HEPATITIS B VACCINATION IN CHILD'S CLASS A O R B PATIENTS W I T H A L C O H O L I C CIRRHOSIS, Manuel Ro~ driguez, Luisa G Dieguez, Monica G Espiga, Mercedes Rodriguez, Rosario F Velazquez, Arancha Alvarez, Luis Rodrigo, Hospital Central de Asturias, Oviedo Spain
VIRAL KINETICS IN HBEAG POSITIVE A N D NEGATIVE PATIENTS W I T H HBV-RELATED CIRRItOSIS TREATED LONG-TERM W I T H LAMIVUDINE. Pietro Lampertico, Mauro Vigano', Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy; Giovanna Lunghi, Anna Orlandi, Laboratory of Virology, IRCCS Maggiore Hospital, Milan Italy; Raffaella Romeo, Massimo A Iavarone, Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy; Ginseppe Colucci, Roche Molecular Systems, Rotkreuz Switzerland; Ersilio Del Ninno, Massimo Colombo, Div Hepatology, IRCCS Maggiore Hospital, University Milan, Milan Italy
BACKGROUND: The i m m u n o g e n i c i t y of HBV vaccination in patients waiting for or after liver transplantation is in general low. However, little is k n o w n about the reactivity of the vaccine in patients with liver cirrhosis in an earlier stage. AIMS: To asses the response rate to hepatitis B vaccination in patients with alcoholic cirrhosis w h o were in C h i l d - P u g h ' s class A or B a n d to identify potential factors interfering with an adequate response. PATIENTS AND METHODS: 94 patients with alcoholic cirrhosis (72 Child's A a n d 22 Child's B class) a n d negative for HBsAg, antiHBc, antiHBs a n d antiHCV in s e r u m were w~ccinated with double dosis (40/xg) of r e c o m b i n a n t vaccine intramuscularly at 0, 1 a n d 6 months. AntiHBs s e r u m levels were determined one m o n t h after the last dosis in all patients a n d subsequently every 6 m o n t h s in responders. Response was considered w h e n antiHBs was -- 10 mIU/ml a n d high-response w h e n it was -> 100 mlU/ml. The effect on the response of 20 clinical a n d biological variables recorded before or d u r i n g vaccination was assessed. Statistical analysis was p e r f o r m e d using Chi-squared a n d s t u d e n t ' s t test a n d the Kaplan-Meier method. RESULTS: Response was obtained in 57/94 (61%) patients (geometric m e a n titer of antiHBs: 2 9 1 2 3 2 9 ) . A m o n g the 20 variables analysed, only a baseline s e r u m albumin -~ 4.3 g/dl (response rate 55% vs. 92%; p = 0 . 0 1 ) was associated with primary n o n r e s p o n s e A high-response was elicited in 34 out of 57 (60%) responders. A m o n g responders, patients with 5 points in the Child-Pugh score achivied higher antiHBs leveIs ( 3 4 9 2 3 6 7 mIU/ ml) than those with more than 5 points (120 2 198 mlU/ml) ( p = 0.002). The cumulative probability to maintain antiHBs levels >-- 10 mlU/ml at 6, 12 a n d 18 m o n t h s after the last dosis was higher in patients with highresponse (100%~ 89% and 76%) than in those with lowresponse (60%, 30% a n d 15%) (p =0.00001). CONCLUSIONS: The rate a n d intensity of response to vaccination against HBV in patients with alcoholic cirrhosis in ChiId's class A or B depend on the grade of liver disfunction. Like in other groups, persistence of antibody is related to the maximal level of antiHBs achived after vaccination. Patients w h o elicit a lowresponse could obtain benefit from booster dosis of vaccine.
Background and Aim. Patients treated long-term with lamivudine are at high risk of developing YMDD mutants, but predictors of virological breakthrough are still poorly defined. Aim of the study was to assess the kinetics of HBV-DNAduring therapy and correlate these findings with antiviraI response and development of YMDD mutants. Patientsand Methods. 50 patients (44 men, 49 yr, 34 HBeAgnegative, 39 cirrhotics) with chronic hepatitis B were treated with lamivudine 100 or 150 rag/daily for 9-51 months (median 30). Patients were checked every two months with liver function tests, HBV-DNAby nou-PCR assays (Digene or bDNA, >1x106 copies/ml), and by quantitative PCR (Amplicor HBV Monitor, Roche, ;>4x102 eopies/ml), and IgM anti-HBc (MEIA, Abbott). YMDD mutants were looked for by direct sequencing using an automated Sequencer (Pharmacia) in patients with a virological breakthrough, defined as reappearance of serum HBV-DNAby non-PCR assays in a patient who initially responded to therapy. Results. At baseline, ALT were 134 IU/L (31-1900), HBV-DNA9x106 copies/ml (3x104->4x107) by quantitative PCR, IgM anti-HBc 0.71 index (0.08~3.35). After 6 months of therapy, 48 (96%) patients had normal ALT levels and 50 (100%) had undetectable HBV-DNA by non-PCR assays. 37 patients maintained normal ALT leveIs and undetectable HBV-DNAby non-PCR assays throughout the study, whereas 13 (26%) developed YMDD mutants between month 8 and 21 (median 13). Serum HBVDNA by quantitative PCR fell below 103 copies/ml in 23 (68%), 29 (86%), and 31 (91%) HBeAg negative patients by month 2, 4 and 6, respectively. The corresponding features for HBeAg positive patients were 1 (6%), 4 (25%) and 6 (37%) (p<0.001). Overall, 9 of 13 (69%) patients with HBV-DNA >103 copies/mI at month 6 developed mutants in the following 18 months of therapy as compared to 4 of 37 (l 1%) patients with < 103 copies/ml (p<0.001). Seroconversion to anti-HBe occurred in 5 of 6 HBeAg positive patients with HBV-DNA < 103 copies/ml at month 6 as compared to 3 of l0 patients with > 103 copies/mI of HBV-DNA. In 10 of 13 patients with YMDD mutants, HBV-DNA by quantitative PCR significantlyincreased to 104-105copies/ml in the 2-6 months prior to the reappearance of HBV-DNAby Digene or bDNA assays. The 37 patients who showed normal ALT levels and undetectable HBV-DNAby Digene or bDNA throughout the 24 months of study, were also tested by quantitative PCR; HBV-DNA remained persistently ondeteetable (<400 copies/ ml) in 13 patients (35%), whereas 103-104copies/ml of HBV-DNAwere identified in at least one serum sample in 24 cases (65%). Conclusions: HBV suppression by lamivudine occurs earlier in HBeAg negative than in HBeAg positive patients. YMDD mutants occur more frequently in patients with > l03 copies/ml HBV-DNA at month 6. Low-level HBV replication is transiently detected by quantitative PCR in many patients without YIVIDDmutants.
18,37
1838
THE RESULTS OF LAMIVUDINE/INTERFERON-ct COMBINATION THERAPY IN CHRONIC HEPATITIS B PATIENTS. Can P Eyigun, A y h a n Kubar, Ali Sengul, Bulent Celasun, Ufuk Dizer, Alaaddin Pahsa, Gulhane Military Medical Academy, Ankara Turkey
INTERFERON ALFA A N D FAMCICLOVIR FOR CHRONIC HBSAG A N D ANTI-HBE POSITIVE PATIENTS - AN INTERIM ANALYSIS. Reel E Sentjens, Marcel Beld, Sjoerd Rebers, Henk W Reesink, AMC, Amsterdam Netherlands
Lamivudine (LAM) and Interferon-o~, (IFN-o0 are effective in inhibiting Hepatitis B Virus (HBV) replication in chronic hepatitis B patients (CHBPs) and used each alone or in combination to treat CHBPs. Aim: To evaluate the efficacy of combination therapy. Methods: Twenty-one CHBPs with eAg+(18M/3F, mean age 30-+6 yrs)(Group AI) and 2I with eAg-(19M/2F, mean age 3I-+6.1 yrs) (Group A2) were treated with 4-.5 or 5 MU 1FN-o:/d and IAM 100mg/d for 9 months in combination and plus 3 months with LAM 100mg/d alone. Twenty-eight CHBPs with eAg+ (24M/4F, mean age 28-+7.lyrs) (Group B1) and 27 with eAg- (27M, mean age 38-+9)(Group 82) were treated with 4.5 or 5 MU IFN-odd and LAM 100mg/d for 9 months in combination and LAM 100mg/d is being still given (mean duration 19.1±6.9 months). The necroinfiammatory activity and fibrosis were evaluated according to modified Knodell scoring system within six months before therapy and six months after IFN-a was stopped. HBV-DNA was assessed by PCR (In house and Cobas amplicor system, Roche, Switzerland). HBsAg, HBeAg and anti-HBe were assessed by EIA (Murex, Abbot Lab.,IL,USA). Results: HBV-DNA was negative in all 4 groups by PCR at the end of IFN-o~ therapy and then became positive in 17 (80.9%)in Group A1,7 (33.3%) in Group A2 and none in group B six months after IFN-o~ was stopped.But virological berakthrough occurred in 3 pts in Gr.B1 and 2 in Gr.B2 at average 23.4-+6.5 months.HBeAg/anti-HBeAgseroconversion was seen in 7 (33.3%)pts, in 15 (53.6%)at the end of 1FN-a therapy in Gr.A1 and Gr.Bl,respectively. In Gr.A1, HBeAg/anti-HBe seroconversion was also found in extra 4 pts while HBeAg was becoming positive in 2 pts six months after IFN-a ended. Improvement in HAI and fibrosis scores was also noted in all groups. Conclusions: 1.LAMAFN-oe combination therapy was found to be effective in treatment of CHBPs.2. LAMBFN-a combination therapy seemed to prevent YMDD mutations.3. LAM should be continued after IFN-oe was stopped.
Objectives: To establish if combination therapy with interferon c~-2a (IFN) and Famciclovir can provoke disappearance of HBsAg a n d HBV DNA. Methods: Twelve treatment-naive chronic HBsAg a n d anti-HBe positive hepatitis B patients received IFN 9 MU t.i.w, combined with Famiclovir 3x500 mg daily for 24 weeks. Serum samples were obtained at week O, 8 a n d 24 during treatment a n d 6 m o n t h s after stopping treatment. HBV DNA levels were determined using the Quantiplex HBV 1.0 bDNA assay (Bayer, detection limit 7x10 s copies/ml). W h e n results were below the detection limit of the bDNA, HBV DNA was measured by qualitative PCR (Roche HBV m o n i t o r 2.0 assay, detection limit 4 x l 0 1 copies/ml). Results: Ten male a n d 2 female patient were studied. All patients were HBsAg positive, HBeAg negative, anti-HBe positive a n d HBVDNA positive as measured by PCR. Mean pretreatment ALAT values were 146 U/L (range 10-800) (upper limit of normal 45 U/L). Mean pretreatment viral load was 5.6 log eopies/ml. The viral load decline after 8 weeks was 2.1 log copies/ml. F r o m week 8 to 24, 5 patients h a d a m e a n viral load increase of 0.5 log, 3 patients h a d a mean viral load decrease of 0.9 log, a n d 4 patients had no change in viral load. During the follow up period 11 patients h a d an increase of viral load of 1.6 log copies/ml the m e a n viral load at the end of follow u p was 4.8 log copies/ml. At the end of treatment 6/12 patients were HBV-DNA negative as measured b y PCR. One of 12 patients remained HBV-DNA negative at the end of the follow up. None of the patients became HBsAg negative at airy time period. Mean ALAT value at 8 weeks of treatment was 70 U/L (range 16-231) and the m e a n ALAT values at the end of treatment a n d at the end of follow up were 94 U/L (range 15-481) a n d 72 U/L (t 1-263) respectively. 5/12 patients h a d normal ALAT values at the end of follow up. Conclusions: A combination therapy of IFN a n d Famciclovir induced in none of the patients disappearance of HBsAg. During therapy HBV DNA levels d r o p p e d but returned to approximately pretreatment levels 6 m o n t h s after stopping therapy.
Table 1. Cllemical Responses of Treated Patients with Hepatitis B
At A2 81 82
Mean Mean Mean Mean AST%SD AST%SO AS'I'3-+SD A L T % S D
Mean Mean A L T % S D ALT3_+SD
91.9±61.6 6&7_+4&l 72±3&1 59.8_+29,2
42,6_+24.7 47±31,5 43.8±22 4&2_+21.1
35.7_15,2 37+_16,1 37,4±14,9 39_+24,5
43,2~2&8 42,3~49,3 26,7_+12.3 24,2_+4.54
168.+,+128 124.3±t17.9 I46,6±100,t 129_+83
1: Baseline 2; At the end of IFN-~ therapy 3: Six months after IFN-ct Therapy
69,5_+64 62±95,8 27_.+25.9 29_+10.8