Bozdayi, Mithat

Bozkaya, Hakan

Erkan, Ozlem

Kocer Sagiroglu, Armagan

Uzunalimoglu, Ozden

Yurdaydin, Cihan

English

ARTS repository - University of Groningen

   University of GroningenLamivudine Is Not Effective in the Treatment of Non-Cirrhotic HBeAg (-) Chronic Hepatitis BPatients with Low Level ViremiaBozkaya, Hakan; Yurdaydin, Cihan; Bozdayi, Mithat; Kocer Sagiroglu, Armagan; Erkan,Ozlem; Uzunalimoglu, OzdenIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2002Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bozkaya, H., Yurdaydin, C., Bozdayi, M., Kocer Sagiroglu, A., Erkan, O., & Uzunalimoglu, O. (2002).Lamivudine Is Not Effective in the Treatment of Non-Cirrhotic HBeAg (-) Chronic Hepatitis B Patients withLow Level Viremia.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 13-02-2023100 Poster Sessions - ~  LAMIVUDINE IS NOT EFFECTIVE IN THE TREATMENT OF NON-CIRRHOTIC HBeAg ( - )  CHRONIC HEPATITIS B PATIENTS WITH LOW LEVEL VIREMIA Hakan Bozkaya 1 , Cihan Yurdaydin 1 , Mithat Bozdayi 2, Armagan Kocer Sagiroglu 2, Ozlem Erkan 2, Ozden Uzunalimoglu. tAnkara University School of Medicine Dept. of Gastroenterology; 2Ankara University Institute of Hepatology, Ankara, Turkey Background: A subgroup of non-cirrhotic e-minus chronic hepatitis B (CHB) patients shows persistent ALT abnormalities despite undetectable HBV DNA by hybridization assays. The effect of antiviral treatment in these patients is not well established. Very sensitive real-time PCR assays may have an impact in the evaluation of the treatment in these pts. Patients and Methods: 18 HBeAg (- ) ,  HBV DNA < 5 pg/ml CHB pa- tients with persistently elevated ALT levels were included. Fourteen of them received 1 year lamivudine treatment (150 mg/qd) while remaining 4 patients had at least 1 year of follow-up without any treatment. Four of 14 treated patients had also more than 1 year of follow-up period before lamivudine treatment. Hence, we compared 14 treatment periods with 8 control periods in a total of 18 patients. HBV DNA was measured by real- time PCR (100 copy/ml) at baseline and at the end of the treatment/control periods. Results: Mean baseline HBV DNA levels of treatment vs. control peri- ods were similar (3.9 x 104 4- 9.6 x 104 vs. 8.4 x 105 4- 2.3 x 106, respectively). None of the lamivudine treated but two control patients had >2 log decrease at the end of the treatment/control periods. Two of 14 (14%) treated patients had ALT normalization while no change in ALT was observed during 8 control periods. Conclusion: Lamivudine is not effective in the treatment of e-minus CHB patients with low level viremia. Lamivudine does not seem to further en- hance the immune response-mediated inhibition of viral replication in these patients. [ - ~  ADEFOVIR AND PHARMACOKINETICS IN DIPIVOXlL SAFETY SUBJECTS WITH HEPATITIS B VIRUS INFECTION AND IN HEALTHY SUBJECTS Brian Kearney, Wanda Knight, Graeme Currie, Desiree Beutelspacher, Ramin Ebrahimi, Stan Gill, John Fry, Carol Brosgart. Clinical Research, Gilead Sciences, Foster City, California, USA Background: Adefovir Dipivoxil (ADV) is being evaluated for the treat- ment of chronic hepatitis B (HBV) infection. The safety and pharmacoki- netics (PK) of ADV in subjects with HBV were investigated and the effect of dosing with and without food was assessed. Food may alter ADV ab- sorption. Objectives: To evaluate the safety and PK of ADV in HBV patients, and evaluate the effect of food on ADV PK. Methods: Fourteen HBV subjects received once dally oral dosing of ADV 10 mg, with PK samples measured after single and multiple doses. Eighteen normal subjects received 2 single doses of ADV 10 mg with and without a high fat meal (separated by 1 week washout), with PK measured after each dose. Safety was assessed via adverse events (AEs) and laboratory parameters. Results: Fourteen HBV subjects (9 males, 5 females, mean age 40 Range: 23-68 years) and 18 normal subjects (10 males, 8 females, mean age 29 Range: 18-41 years) completed the studies. No serious AEs or discontin- uations occurred with either group. ADV was well tolerated in all sub- jects. ADV PK in HBV subjects were similar following single (AUC 210 ng*hr/mL, Cmax 17.5 ng/mL) and multiple (AUC 204 ng*hr/mL, Cmax 18.3 ng/mL) dosing Cmax and AUC in HBV patients after single and mul- tiple dosing were not different to those seen in healthy subjects (AUC 192 ng*hr/mL, Cmax 20.4 ng/mL). Conclusion: ADV pharmacokinetics were similar in HBV and healthy subjects. There was no significant food effect, therefore ADV may be taken without regard to meals. - ~ A  DRUG-DRUG INTERACTION STUDY BETWEEN ADEFOVIR DIPIVOXlL AND LAMIVUDINE, ACETAMINOPHEN, IBUPROFEN AND TRIMETHOPRIM/SULFAMETHOXAZOLE Brian Kearney, Wanda Knight, Graeme Currie, Jennifer Contreras, John Wolf, Stan Gill, John Fry, Carol Brosgart. Clinical Research, Gilead Sciences, Foster City, California, USA Background: Coadministration of adefovir dipivoxil (ADV) and lamivu- dine (LAM) for the treatment of HBV-infection is currently being evalu- ated. In Phase 3 clinical trials of ADV, the most frequently coadministered medications were acetaminophen (APAP), ibuprofen (IBU) and antibiotics, including tdmethoprim/sulfamethoxazole (TMP/SMX). It is important to understand the drug interaction potential of these agents with ADV, es- pecially as APAP can cause hepatotoxicty and IBU can result in renal impairment. Objectives: To determine whether coadministration of ADV 10 mg with LAM 100 mg QD, APAP 1000 mg QID, IBU 800 mg TID, or TMP/SMX 160/800 mg BID affected the steady-state pharmacokinetics (PK) of either drug such that dosing modifications would be required. Methods: Each subject was randomized to an interaction cohort and the order of three treatments (ADV alone, ADV+test drug, test drug alone), each treatment separated by a 7-day washout. Alterations in PK (Cmax and AUC) were assessed using equivalence testing (coadministered vs. dosed alone). Results: The PK of LAM, APAP, IBU, TMP/SMX were equivalent when dosed with ADV. There were no alterations in the PK of ADV when coad- ministered with these agents, except for when coadministered with IBU, where small increases in the Cmax (33%), AUC (23%), and urinary recov- ery (23%) were observed, without a change in renal clearance, suggesting enhanced bioavailability of adefovir. Condusions-" The PK of ADV and LAM, APAP, and TMP/SMX were unaltered by their coadministration. IBU PK was unaffected by ADV. The small increase in adefovir exposure when dosed with IBU is not of suffi- cient magnitude to necessitate a change in dose. ~-4 - I  EFFICACY OF A SHORT-SCHEDULE/HIGH DOSE HEPATITIS B VACCINATION IN DRUG USERS Suzanne Brissette 1, Marina Gomez 1, Jean Lambert 2, Bernard Willems 1. 1 Centre Hospitalier De L'Universite De Montreal, Unite De Desintoxication, Montreal, Quebec; 2Centre Hospitalier De L'Universite De Montreal, Unite De Desintoxication, Montreal, Quebec, Canada Objectives: To evaluate the response rates and compliance to 4 vaccination programs of Hepatitis B vaccination in drug users. Methods: 908 cocaine/heroin users were randomised to 4 groups (2 sched- ules (standard (0, 4, 24 weeks) or shorter (0, 2, 4 weeks)) and 2 doses of vaccine (Recombivax 10 microg or 40 microg). Response was defined as levels of anti-HBsAg > 10 IU/L. Compliance was determined as having received 3 injections of the vaccine. Results: Compliance to the vaccination was better in the short schedule groups (73.7% vs 46.6%; p < 0.001; N = 771). Amongst these, 389 came back for anti-HBs measurement. Their overall response rate was 77.9%, lower than in the general population. The short schedule/high dose group developed comparable response rates to the standard schedule and dose group (82.4% vs 81.5%); the short schedule/standard dose had lower re- sponse rates (57.3%). Standard calendar Short calendar I0 microg 81.5% 57.3% 40 microg 93.0% 82.4% Chi2:38.825 (p < 0.000) Multivariate analysis showed that the 40 microg dose was positively associ- ated to the response (OR: 4.731; CI 2.579-8.678) while HCV (OR: 0.300; CI 0.155-0.581) the short schedule (OR: 0.316; CI 0.174-0.573) and age 

Lamivudine Is Not Effective in the Treatment of Non-Cirrhotic HBeAg (-) Chronic Hepatitis B Patients with Low Level Viremia

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Lamivudine Is Not Effective in the Treatment of Non-Cirrhotic HBeAg (-) Chronic Hepatitis B Patients with Low Level Viremia

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