773 SERUM HEPATITIS B SURFACE ANTIGEN LEVELS TO GUIDE THE CESSATION OF ENTECAVIR IN HEPATITIS B e ANTIGEN-NEGATIVE CHRONIC HEPATITIS B: AN INTERIM ANALYSIS

POSTERS 773 SERUM HEPATITIS B SURFACE ANTIGEN LEVELS TO GUIDE THE CESSATION OF ENTECAVIR IN HEPATITIS B e ANTIGEN-NEGATIVE CHRONIC HEPATITIS B: AN INTERIM ANALYSIS W.-K. Seto1 , A.J. Hui2 , V.W.-S. Wong3 , G.L.-H. Wong3 , K. Liu1 , C.-L. Lai1 , M.-F. Yuen1 , H.L.-Y. Chan3 . 1 Medicine, The University of Hong Kong, Queen Mary Hospital, 2 Medicine, Alice Ho Miu Ling Nethersole Hospital, 3 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong S.A.R. E-mail: [email protected] Background: Cessation of nucleoside analogue therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is controversial. It is uncertain whether serum hepatitis B surface antigen (HBsAg) levels can predict virologic kinetics after treatment cessation. Methods: Entecavir was stopped in HBeAg-negative patients treated for at least 2 years with no co-existing or decompensated liver disease. All patients had undetectable HBV DNA levels on at least 3 separate occasions 6 months apart before treatment cessation. Serum HBsAg (Elecsys II, lower limit of detection 0.05 IU/mL), HBV DNA (Cobas Taqman, lower limit of detection 20 IU/mL) and liver biochemistry were monitored at every 6–12 weeks for 1 year. Entecavir was restarted if virologic relapse, defined as HBV DNA >2,000 IU/mL occurred. The primary endpoint was sustained virologic remission, defined as HBV DNA persistently ≤200 IU/mL. Results: 184 patients (median age 54 years, 67.9% male) were recruited. The median baseline HBsAg level was 892 (range 2.3–24,100) IU/mL. Median duration of entecavir therapy before cessation was 3.05 (range 2.02–5.95) years. At the time of writing, 158 (85.9%) and 104 (56.2%) patients have been followed up for 12 and 24 weeks respectively. The cumulative rates of virologic relapse, calculated using the Kaplan–Meier method, were 11.2% at week 12 and 78.1% at week 24 respectively. Among patients with 24 weeks of follow-up (n = 104), patients achieving sustained virologic remission (n = 9), when compared to patients without virologic remission (n = 93) had a significantly longer median duration of entecavir treatment before therapy cessation (4.05 and 3.03 years respectively, p = 0.007), a higher probability of undetectable viremia at week 12 (88.9% and 17.9% respectively, p < 0.001) and a trend towards a lower median baseline HBsAg level (701 and 936 IU/mL respectively, p = 0.088). Conclusion: Base on this interim analysis, a longer duration of prior nucleoside analogue therapy and off-treatment HBV DNA undetectability at week 12 were associated with a higher chance of sustained virologic remission after treatment cessation. Subsequent analysis would determine if baseline and off-treatment HBsAg levels could predict virologic remission after treatment cessation. Acknowledgement: This study was supported by an unrestricted grant from Roche Diagnostics

or 6 months off-treatment follow-up. Flares were host-induced (ALT elevation followed by HBV DNA decline, n = 19), virus-induced (HBV DNA increase with subsequent ALT elevation, n = 17) or indeterminate (n = 14). Presence of wildtype (WT) or non-WT (detectable PC/BCP mutants) was studied by lineprobe assay. Results: 104 patients were treated with PEG-IFN alone, HBV genotype frequencies (A/B/C/D/other) were 74/19/29/85/7 and 76 patients had only WT. Fifty-eight percent of host-induced flares occurred in WT HBV patients, whereas 94% virus-induced flares occurred in patients with PC and/or BCP mutants (p = 0.003). HBsAg loss was only achieved in patients with a host-induced flare, and WT patients with a host-induced flare cleared HBsAg in 64%. Analysis of individual patient data revealed that serum HBsAg levels only declined after a host-induced flare, whereas virus-induced flares were accompanied by stable or increasing levels of HBsAg (figures). Patients with a host-induced flare achieved a mean HBsAg reduction of 3.24 logIU/mL by 6 months post-treatment, compared to 0.25 logIU/mL in virus-induced flares (p < 0.001). Patients who achieved a decline in HBsAg of more than 0.5 logIU/mL within four weeks after the flare cleared HBsAg in 64% (7/11), increasing to 75% (6/8) in patients with a decline >1 logIU/mL (p < 0.001). Conclusions: Host-induced flares are associated with presence of WT virus and may result in decline and clearance of HBV DNA, HBeAg and HBsAg. Monitoring of HBsAg levels during and after flares may help predict a favourable treatment outcome.

Figure 1. Host induced flare.

774 CLOSE MONITORING OF HBsAg LEVELS HELPS CLASSIFY FLARES DURING PEGINTERFERON THERAPY AND PREDICTS TREATMENT RESPONSE M.J. Sonneveld1 , R. Zoutendijk1 , H.J. Flink1 , L. Zwang1 , B.E. Hansen1,2 , H.L. Janssen1 . 1 Gastroenterology and Hepatology, 2 Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: [email protected] Background: ALT flares occur frequently during peginterferon (PEG-IFN) therapy. We related occurrence of flares to presence of precore (PC) and/or core promoter (BCP) HBV mutants and studied kinetics of HBeAg and HBsAg levels during flares. Methods: Fifty of 214 (23%) patients treated with PEGIFN±lamivudine for 52 weeks experienced flares during treatment

Figure 2. Virus induced flare.

Journal of Hepatology 2013 vol. 58 | S229–S407

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