1 / 33

Hepatitis B: predictors and endpoints revisited

Hepatitis B: predictors and endpoints revisited? . Rami MOUCARI, MDHpital Beaujon, France. Rational . Durable virological remission Finite period of treatment HBsAg clearance (closest to cure). History. A 52-year-old white female HBsAg positive test ordered by her internist Multiple risk factors including: multiple sexual partners and multiple tattoos and piercings. She has no history of injection drug use, or of excessive alcohol intake..

rigg
Download Presentation

Hepatitis B: predictors and endpoints revisited

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


    2. Hepatitis B: predictors and endpoints revisited? Rami MOUCARI, MD Hôpital Beaujon, France

    3. Rational Durable virological remission Finite period of treatment HBsAg clearance (closest to cure)

    4. History A 52-year-old white female HBsAg positive test ordered by her internist Multiple risk factors including: multiple sexual partners and multiple tattoos and piercings. She has no history of injection drug use, or of excessive alcohol intake.

    5. Current Presentation She is referred to you for workup and management of her hepatitis B. You order laboratory testing that reveals: Hepatitis B antigen HBeAg–negative disease HBV DNA: 107 IU/mL Alanine aminotransferase (ALT): 95 IU/L Aspartate aminotransferase (AST): 75 IU/L Alpha-fetoprotein (AFP): 22 µg/L Platelet count: 152,000/mm3 Albumin: 3.8 g/dL Bilirubin: 1.0 mg/dL International normalized ratio (INR): 1.1

    6. How would you manage the patient at this time? A. HBV Genotype B. Abdominal Ultrasound C. Perform a Liver Biospy D. Start Antiviral Therapy

    7. Investigations HBV Genotype : D Abdominal Ultrasound: no evidence of cancer or liver mass. Liver Biopsy: A2F2 (METAVIR). No steatosis

    8. Which of the following agents would be preferable for this patient? A. Pegylated Interferon Alfa-2a B. Telbivudine C. Tenofovir D. Entecavir

    9. Pegylated Interferon Therapy

    10. What is Your Preferred Strategy A. Add Entecavir B. Add Telbivudine C. Add Tenofovir D. Prolong Treatment Duration with Pegylated Interferon Alfa-2a

    13. IFN-Long-Term Results HBsAg

    16. HBsAg – Peginterferon Alfa 2a

    17. Baseline Predictors Of Response Multivariate Analysis Significant predictors of sustained response: Age & Gender High baseline ALT Low baseline HBV DNA HBV Genotype

    18. Early Serum HBsAg Drop: A Strong Predictor of Sustained Virological Response to Pegylated Interferon Alfa-2a in HBeAg-Negative Patients Moucari et al. Hepatology 2009

    19. Patients 48 consecutive HBeAg-negative patients Pegylated Interferon alfa-2a /180 micrograms per week / 48 weeks. End of treatment (EOT) response: undetectable serum HBV DNA at the EOT SVR: undetectable serum HBV DNA 24 weeks after treatment cessation Follow-up: 48 weeks after treatment cessation

    20. Methods HBV genotype: TRUGENE HBV genotyping kit Baseline, Treatment weeks 12, 24 and 48 and Follow-up weeks 72 and 96: Serum HBV DNA: TaqMan polymerase chain reaction assay (COBAS TaqMan, Roche Molecular System – lower limit of detection =70 copies/mL) Serum HBsAg: Abbott Architect HBsAg QT assay (limits of detection: 0.05 – 125 000 IU/mL)

    21. Baseline Characteristics

    22. Virological Response

    30. Conclusion (1) HBsAg clearance = closest to cure in chronic HBV infection Reduced rate of cirrhosis and HCC Improved survival HBsAg clearance is achievable in a high steady rate in CHB patients responding to IFN therapy

    31. Conclusion (2) Serum quantitative HBsAg seems to be an excellent on-treatment marker predicting sustained off-treatment response, and identifying in the early phase of PEG-IFN therapy the patients who are most likely to benefit from this treatment.

    32. Virologic Response in HBeAg- Patients (Undetectable HBV DNA at Year 1) ADV, adefovir; ETV, entecavir; HBeAg, hepatitis B e antigen; LAM, lamivudine; LdT, telbivudine; LLD, lower level of detection TDF, tenofovir disoproxil fumarate; PegIFN, peginterferon; PCR, polymerase chain reaction; PLB, placebo. The next slide shows data on virologic response in HBeAg-negative patients with chronic hepatitis B in response to various treatments. The Y axis shows the percentage of patients with undetectable HBV DNA after 1 year of treatment with the different agents listed on the X axis. In comparison to the data on HBeAg-positive patients, the achievement of undetectable HBV DNA is very high, approximately 90% or higher. The most significant factor underlying this increased HBV DNA clearance is that HBeAg-negative patients normally exhibit a pretreatment HBV DNA approximately 2 logs lower than HBeAg-positive patients. Therefore, since the baseline HBV DNA is lower, it is easier to achieve undetectable HBV DNA in HBeAg-negative patients. For more information, go online to: http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Boston%202007/Tracks/HBV%20Treatment/Capsules/LB2.aspxADV, adefovir; ETV, entecavir; HBeAg, hepatitis B e antigen; LAM, lamivudine; LdT, telbivudine; LLD, lower level of detection TDF, tenofovir disoproxil fumarate; PegIFN, peginterferon; PCR, polymerase chain reaction; PLB, placebo. The next slide shows data on virologic response in HBeAg-negative patients with chronic hepatitis B in response to various treatments. The Y axis shows the percentage of patients with undetectable HBV DNA after 1 year of treatment with the different agents listed on the X axis. In comparison to the data on HBeAg-positive patients, the achievement of undetectable HBV DNA is very high, approximately 90% or higher. The most significant factor underlying this increased HBV DNA clearance is that HBeAg-negative patients normally exhibit a pretreatment HBV DNA approximately 2 logs lower than HBeAg-positive patients. Therefore, since the baseline HBV DNA is lower, it is easier to achieve undetectable HBV DNA in HBeAg-negative patients. For more information, go online to: http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Boston%202007/Tracks/HBV%20Treatment/Capsules/LB2.aspx

    34. HBsAg Loss in HBeAg-Negative Patients Following Long-term Adefovir Treatment 33 HBeAg-negative CHB patients Adefovir for 4-5 years with undetectable HBV DNA 4 years of follow-up after Adefovir discontinuation 18 of 33 patients (55%): SVR 9/18 (50%): HBsAg Clearance

More Related