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49 Association between HBeAg seroconversion and sustained HBV-DNA suppression in patients treated with peginterferon alpha-2a (40KD) (PEGASYS) for HBeAg-positive chronic hepatitis B (CHB)
Parallel Session 5: HEPATITIS B DISEASE AND THERAPY INTERFERON THERAPY REDUCES CIRRHOSIS AND HEPATOCELLULAR CARCINOMA IN HBeAg POSITIVE CHRONIC HEPATITIS B S.M. Lin 1, M.L. Yu3, C.M. Lee 2, R.N. Chien 1, I.S. Sheen 1, C.M. Chu 1, Y.E Liaw 1. 1Liver Researeh Unit, Chang Gung Memorial Hospital,
Taipei, Taiwan," 2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Taiwan," SLiver Unit, Chang Gung Memorial Hospital-Kaohsiung, Taiwan Background: The long-term outcomes of interferon-a (IFN) therapy in hepatitis B e antigen (HBeAg) seropositive patients with chronic hepatitis B remains controversial. The aim of this study is to elucidate the role of IFN therapy in the prevention of cirrhosis and hepatocellular carcinoma (HCC). Methods: This is a prospective cohort study from three medical centers. Two hundred thirty-three IFN-treated patients and 1:1 well-matched 233 untreated patients. Patients in treated group received IFN therapy with or without prednisolone priming. Blood biochemical tests, virological markers, HBV-DNA and genotype, alpha-fetoprotein (AFP) and abdominal sonography were measured. Results: At the end of 11 years of follow-up (median 6.8 years, range 1.1 to 16.5 years), the cumulative incidence of HBeAg seroconversion was 74.6% in the IFN-treated group and 51.7% in the control group (P 0.031); that of cirrhosis was 33.7% in the control group and 17.8% in the IFNtreated group (P 0.041); and that of hepatocellular carcinoma (HCC) was 12.5 % in the control group and 2.7% in the IFN-treated group (P 0.011). Compared with untreated controls with persistent HBeAg, HBeAg seroconverters in the untreated and IFN-treated groups showed signficantly lower incidence of cirrhosis and HCC (P 0.003 to 0.031), while non-seroconverters of the IFN-treated group had modestly lower incidence of cirrhosis (P 0.065). Hepatitis B surface antigen (HBsAg) seroclearance occurred in 3% of IFN-treated patients (vs 0.4% in controls, P 0.03). Patients with genotype B infection showed higher rate of HBeAg seroconversion and reduced rate of cirrhosis and HCC than patients with genotype C infection in both the IFN-treated and the untreated group. Conclusions: IFN therapy in HBeAg positive patients increases cumulative HBeAg seroconversion and reduces cirrhosis and HCC development.
I•
ASSOCIATION BETWEEN HBeAg SEROCONVERSION AND SUSTAINED HBV-DNA SUPPRESSION IN PATIENTS TREATED WITH PEGINTERFERON ALPHA-2a (40KD) (PEGASYS) FOR HBeAg-POSITIVE CHRONIC HEPATITIS B (CHB)
T. Piratvisuthl, G.K.K. Lau 2, R Marcellin 3, W.C. Chow4, G. Cooksley 5, M.W. Fried 6, S.W. Paik 7, Y.F. Liaw8, M. Popescu9, R Button 1~
$23
HBeAg seroconversion and HBV-DNA suppression in patients treated with peginterferon ~-2a (40KD) [PEGASYS] in a large, randomized study. Patients and Methods: HBeAg-positive patients (n 271) received 48 weeks of 180 gg peginterferon ~-2a once-weekly and were assessed 24 weeks post-treatment. HBeAg and HBV-DNA were measured throughout the study using the Abbott AxSYM test and the Roche COBAS AMPLICOR HBV MONITOR, respectively. Results: Overall, 87 (32%) and 8 (3%) patients had HBeAg seroconversion and HBsAg seroconversion, respectively, at week 72. Mean baseline HBV-DNA levels in patients with HBeAg seroconversion at week 72 were lower (9.13 log cp/ml) than in patients without (10.21 log cp/ml). The reduction in mean HBV-DNA levels between baseline and the end-of-treatment was greater in patients with HBeAg seroconversion at week 72 than those without ( 5.841og cp/ml vs. 3.81og cp/ml). Levels of HBV DNA according to HBeAg response and the start-time of sustained HBeAg seroconversion are shown in the table. Throughout treatment and follow-up, the percentage of patients with HBV DNA <4 log copies/ml was greater in those with HBeAg seroconversion than in those without. Moreover, the highest percentages of patients with HBV DNA below 4 log were seen among those with HBeAg seroconversion starting before or at week 24. Five of the 29 patients (17%) who achieved this 'early' sustained HBeAg seroconversion achieved HBsAg seroconversion by week 72.
HBV DNA <4 lOgl0 cp/inl at
With HBeAg seroconv. (n 87)
Start of sustainedHBeAgseroconv,a ~
>wk24 ~
>wk48 (n 33)
Without HBeAg seroconv. (n 184)
wk 12 wk 24 wk 48 wk 72
31 (36%) 47 (54%) 66 (76%) 57 (66%)
16 (55%) 23 (79%) 26 (90%) 23 (79%)
5 (20%) 8 (32%) 20 (80%) 14 (56%)
10 (30%) 16 (48%) 20 (61%) 20 (61%)
21 (11%) 31 (17%) 43 (23%) 7 (4%)
aHBeAgseroconversionsustainedthroughto week72. Conclusions: Peginterferon a-2a-induced HBeAg seroconversion is associated with sustained reductions in HBV DNA. In patients treated with peginterferon ~-2a, 'early' sustained HBeAg seroconversion greatly increased the chance of early HBsAg clearance.
I - ~ DURABILITY OF RESPONSE AND OCCURRENCE OF LATE RESPONSE TO PEGINTERFERON ALPHA-2a (40KD) [PEGASYS] ONE YEAR POST-TREATMENT IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B G.K.K. Lau 1 , T. Piratvisuth2, K.X. Luo 3, R Marcellin 4, S. Thongsawat5, G. Cooksley6, E. Gane 7, M.W. Fried 8, M. Popescu9, J. Wu 1~ 1Department
1Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand," 2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," 3Service d'H@atologie, H@ital Beaujon, Clichy, France," 4Gastroenterology Department, Singapore General Hospital, Singapore," 5Clinical Research Department, Royal Brisbane Hospital, Brisbane, Australia," 6University of North Carolina Liver Program, University of North Carolina, Chapel Hill, NC, USA," 7Department of Gastroenterology, Samsung Medical Center Seoul, South Korea," 8Chang Gung Memorial Hospital, Linkou, Taiwan," 9Roehe, Basel, Switzerland," l~ Dee Why, Australia
of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," 2Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand," 3Department of Infectious Diseases, Nangfang Hospital, Guangzhou, China," 4Service d 'H@atologie, H@ital Beaujon, Clichy, France," 5Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand," 6Clinical Researeh Department, Royal Brisbane Hospital, Brisbane, Australia," 7Gastroenterology Department, Middlemore Hospital, Otahuhu, New Zealand," 8University of North Carolina Liver Program, University of North Carolina, Chapel Hill, NC, USA," 9Roehe, Basel, Switzerland," l~ Dee Why, Australia
Introduction: HBeAg seroconversion is associated with clearance of HBsAg and improved survival. Recent evidence from large cohort studies suggests that CHB patients with HBV-DNA levels below 4log copies/ml have a markedly reduced risk of developing serious clinical events such as liver cirrhosis or hepatocellular carcinoma (Chen et al., EASL 2005; Iloeje et al., EASL 2005). We investigated the relationship between
B a c k g r o u n d and Aims: In patients with HBeAg-positive chronic hepatitis B (CHB), peginterferon ~-2a (40KD) [PEGASYS] provides significantly higher rates of HBeAg seroconversion and HBV DNA response (HBV DNA <100,000 copies/ml) 6 months post-treatment versus lamivudine [Lau, NEJM 2005]. We evaluated response 1 year after the end-oftreatment in patients receiving peginterferon ~-2a alone.
Taipei, Taiwan," 2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Taiwan," SLiver Unit, Chang Gung Memorial Hospital-Kaohsiung, Taiwan Background: The long-term outcomes of interferon-a (IFN) therapy in hepatitis B e antigen (HBeAg) seropositive patients with chronic hepatitis B remains controversial. The aim of this study is to elucidate the role of IFN therapy in the prevention of cirrhosis and hepatocellular carcinoma (HCC). Methods: This is a prospective cohort study from three medical centers. Two hundred thirty-three IFN-treated patients and 1:1 well-matched 233 untreated patients. Patients in treated group received IFN therapy with or without prednisolone priming. Blood biochemical tests, virological markers, HBV-DNA and genotype, alpha-fetoprotein (AFP) and abdominal sonography were measured. Results: At the end of 11 years of follow-up (median 6.8 years, range 1.1 to 16.5 years), the cumulative incidence of HBeAg seroconversion was 74.6% in the IFN-treated group and 51.7% in the control group (P 0.031); that of cirrhosis was 33.7% in the control group and 17.8% in the IFNtreated group (P 0.041); and that of hepatocellular carcinoma (HCC) was 12.5 % in the control group and 2.7% in the IFN-treated group (P 0.011). Compared with untreated controls with persistent HBeAg, HBeAg seroconverters in the untreated and IFN-treated groups showed signficantly lower incidence of cirrhosis and HCC (P 0.003 to 0.031), while non-seroconverters of the IFN-treated group had modestly lower incidence of cirrhosis (P 0.065). Hepatitis B surface antigen (HBsAg) seroclearance occurred in 3% of IFN-treated patients (vs 0.4% in controls, P 0.03). Patients with genotype B infection showed higher rate of HBeAg seroconversion and reduced rate of cirrhosis and HCC than patients with genotype C infection in both the IFN-treated and the untreated group. Conclusions: IFN therapy in HBeAg positive patients increases cumulative HBeAg seroconversion and reduces cirrhosis and HCC development.
I•
ASSOCIATION BETWEEN HBeAg SEROCONVERSION AND SUSTAINED HBV-DNA SUPPRESSION IN PATIENTS TREATED WITH PEGINTERFERON ALPHA-2a (40KD) (PEGASYS) FOR HBeAg-POSITIVE CHRONIC HEPATITIS B (CHB)
T. Piratvisuthl, G.K.K. Lau 2, R Marcellin 3, W.C. Chow4, G. Cooksley 5, M.W. Fried 6, S.W. Paik 7, Y.F. Liaw8, M. Popescu9, R Button 1~
$23
HBeAg seroconversion and HBV-DNA suppression in patients treated with peginterferon ~-2a (40KD) [PEGASYS] in a large, randomized study. Patients and Methods: HBeAg-positive patients (n 271) received 48 weeks of 180 gg peginterferon ~-2a once-weekly and were assessed 24 weeks post-treatment. HBeAg and HBV-DNA were measured throughout the study using the Abbott AxSYM test and the Roche COBAS AMPLICOR HBV MONITOR, respectively. Results: Overall, 87 (32%) and 8 (3%) patients had HBeAg seroconversion and HBsAg seroconversion, respectively, at week 72. Mean baseline HBV-DNA levels in patients with HBeAg seroconversion at week 72 were lower (9.13 log cp/ml) than in patients without (10.21 log cp/ml). The reduction in mean HBV-DNA levels between baseline and the end-of-treatment was greater in patients with HBeAg seroconversion at week 72 than those without ( 5.841og cp/ml vs. 3.81og cp/ml). Levels of HBV DNA according to HBeAg response and the start-time of sustained HBeAg seroconversion are shown in the table. Throughout treatment and follow-up, the percentage of patients with HBV DNA <4 log copies/ml was greater in those with HBeAg seroconversion than in those without. Moreover, the highest percentages of patients with HBV DNA below 4 log were seen among those with HBeAg seroconversion starting before or at week 24. Five of the 29 patients (17%) who achieved this 'early' sustained HBeAg seroconversion achieved HBsAg seroconversion by week 72.
HBV DNA <4 lOgl0 cp/inl at
With HBeAg seroconv. (n 87)
Start of sustainedHBeAgseroconv,a ~
>wk24 ~
>wk48 (n 33)
Without HBeAg seroconv. (n 184)
wk 12 wk 24 wk 48 wk 72
31 (36%) 47 (54%) 66 (76%) 57 (66%)
16 (55%) 23 (79%) 26 (90%) 23 (79%)
5 (20%) 8 (32%) 20 (80%) 14 (56%)
10 (30%) 16 (48%) 20 (61%) 20 (61%)
21 (11%) 31 (17%) 43 (23%) 7 (4%)
aHBeAgseroconversionsustainedthroughto week72. Conclusions: Peginterferon a-2a-induced HBeAg seroconversion is associated with sustained reductions in HBV DNA. In patients treated with peginterferon ~-2a, 'early' sustained HBeAg seroconversion greatly increased the chance of early HBsAg clearance.
I - ~ DURABILITY OF RESPONSE AND OCCURRENCE OF LATE RESPONSE TO PEGINTERFERON ALPHA-2a (40KD) [PEGASYS] ONE YEAR POST-TREATMENT IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B G.K.K. Lau 1 , T. Piratvisuth2, K.X. Luo 3, R Marcellin 4, S. Thongsawat5, G. Cooksley6, E. Gane 7, M.W. Fried 8, M. Popescu9, J. Wu 1~ 1Department
1Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand," 2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," 3Service d'H@atologie, H@ital Beaujon, Clichy, France," 4Gastroenterology Department, Singapore General Hospital, Singapore," 5Clinical Research Department, Royal Brisbane Hospital, Brisbane, Australia," 6University of North Carolina Liver Program, University of North Carolina, Chapel Hill, NC, USA," 7Department of Gastroenterology, Samsung Medical Center Seoul, South Korea," 8Chang Gung Memorial Hospital, Linkou, Taiwan," 9Roehe, Basel, Switzerland," l~ Dee Why, Australia
of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," 2Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand," 3Department of Infectious Diseases, Nangfang Hospital, Guangzhou, China," 4Service d 'H@atologie, H@ital Beaujon, Clichy, France," 5Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand," 6Clinical Researeh Department, Royal Brisbane Hospital, Brisbane, Australia," 7Gastroenterology Department, Middlemore Hospital, Otahuhu, New Zealand," 8University of North Carolina Liver Program, University of North Carolina, Chapel Hill, NC, USA," 9Roehe, Basel, Switzerland," l~ Dee Why, Australia
Introduction: HBeAg seroconversion is associated with clearance of HBsAg and improved survival. Recent evidence from large cohort studies suggests that CHB patients with HBV-DNA levels below 4log copies/ml have a markedly reduced risk of developing serious clinical events such as liver cirrhosis or hepatocellular carcinoma (Chen et al., EASL 2005; Iloeje et al., EASL 2005). We investigated the relationship between
B a c k g r o u n d and Aims: In patients with HBeAg-positive chronic hepatitis B (CHB), peginterferon ~-2a (40KD) [PEGASYS] provides significantly higher rates of HBeAg seroconversion and HBV DNA response (HBV DNA <100,000 copies/ml) 6 months post-treatment versus lamivudine [Lau, NEJM 2005]. We evaluated response 1 year after the end-oftreatment in patients receiving peginterferon ~-2a alone.