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Bài giảng Hepatitis B Reactivation: A Largely Preventable Problem

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  1. Hepatitis B Reactivation: A Largely Preventable Problem Jordan J. Feld, MD, MPH Assistant Professor of Medicine University of Toronto Hepatologist Toronto Western Hospital Liver Centre McLaughlin-Rotman Centre for Global Health Toronto, Ontario, Canada This program is supported by an educational grant from
  2. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
  3. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Faculty Disclosures  Jordan J. Feld, MD, MPH has disclosed that he has received consulting fees from Gilead Sciences
  4. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Outline  The problem – Brief background on HBV – Definitions of HBV reactivation  The treatment – The role and timing of antiviral therapy  HBV screening – Who to screen with what tests  Special situations – Lone anti-HBc positive, rituximab, BMT, reactivation in nononcology settings
  5. Introduction to HBV Reactivation
  6. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Hepatitis B: Some Sobering Facts Prevalence of HBsAg High ≥ 8% Intermediate 2% to 7% Low < 2%  350 million people chronically infected  2 billion with evidence of past or present infection  Country of origin is THE major risk factor World Health Organization. Hepatitis B Fact Sheet. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press; 2012.
  7. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Natural History of Chronic HBV Infection Immunotolerance Immune Clearance Immune Control (Nonreplicative) HBV DNA HBeAg+ HBeAg- HBeAb+ HBsAg+ HBsAg- HBsAb+ ALT 5-30 Yrs Mos-Yrs Mos-Yrs Infection Yim HJ, et al. Hepatology. 2006;43:S173-S181.
  8. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Natural History of Chronic HBV Infection Immunotolerance Immune Clearance Immune Control (Nonreplicative) HBV DNA Most Oncology Patients  Normal ALT  Low/undetectable HBV DNA  HBsAg+ and HBeAg-  or HBsAg-, anti-HBc+ HBeAg+ HBeAg- HBeAb+ HBsAg+ HBsAg- HBsAb+ ALT 5-30 Yrs Mos-Yrs Mos-Yrs Infection Yim HJ, et al. Hepatology. 2006;43:S173-S181.
  9. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Do You Ever Really Get Rid of HBV? cccDNA  Immune control—not clearance  “Resolved HBV” a misnomer—still HBV DNA in liver Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
  10. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Do You Ever Really Get Rid of HBV? cccDNA  Immune control—not clearance  “Resolved HBV” a misnomer—still HBV DNA in liver Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
  11. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Do You Ever Really Get Rid of HBV? T cell cccDNA T cell T cell  Immune control—not clearance  “Resolved HBV” a misnomer—still HBV DNA in liver Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
  12. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Along Comes Immune Suppression T cell HIV cccDNA Steroids T cell Chemotx T cell  Immune control can be lost  Immune-mediated liver damage with immune reconstitution Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
  13. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Along Comes Immune Suppression T cell HIV cccDNA Steroids T cell Chemotx T cell  Immune control can be lost  Immune-mediated liver damage with immune reconstitution Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
  14. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis HBV Reactivation HBeAg+ HBeAg- HBeAb+ HBeAg+ Immunotolerance Immune Clearance HBV DNA ALT 5-30 Yrs Mos-Yrs Mos-Yrs Infection Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
  15. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis HBV Reactivation HBeAg+ HBeAg- HBeAb+ HBeAg+ Immunotolerance Immune Suppression Immune Clearance HBV DNA ALT 5-30 Yrs Mos-Yrs Mos-Yrs Infection Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
  16. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis HBV Reactivation HBeAg+ HBeAg- HBeAb+ HBeAg+ Immunotolerance Immune Suppression Immune Reconstitution Immune Clearance HBV DNA ALT 5-30 Yrs Mos-Yrs Mos-Yrs Infection Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
  17. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis HBV Reactivation Definition  Loss of HBV immune control in a patient with inactive or “resolved” HBV infection  Abrupt reappearance or increase in viral replication with liver damage occurring during and/or following immune reconstitution Clinically  Range from subclinical to severe/fatal hepatitis  Rise in HBV DNA ± return of HBeAg  ALT increase (may be mild or very dramatic)  May progress to liver failure/death despite antiviral therapy Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
  18. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Subset of Agents Reported to Cause HBV Reactivation Class Agents Corticosteroids Dexamethasone, methylprednisolone, prednisolone Antitumor antibiotics Actinomycin D, bleomycin, daunorubicin, doxorubicin, epirubicin, mitomycin-C Plant alkaloids Vinblastine, vincristine Alkylating agents Carboplatin, chlorambucil, cisplatin, cyclophosphamide, ifosfamide Antimetabolites Azauridine, cytarabine, fluouracil, gemcitabine, mercaptopurine, methotrexate, thioguanine Monoclonal antibodies Alemtuzumab, rituximab Others Colaspase, docetaxel, etoposide, fludarabine, folinic acid, interferon, procarbazine Yeo W, et al. Hepatology. 2006;43:209-220.
  19. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Case 1: Patient With Breast Cancer  52-yr-old Asian woman presents with stage IIIb breast cancer (ER negative, HER2 negative)  Past medical history: hypertension  Medications: hydrochlorothiazide  No history of liver disease  Scheduled for surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin followed by paclitaxel  CBC/electrolytes/creatinine: normal  ALT: 18 U/L
  20. Hepatitis B Reactivation: A Largely Preventable Problem clinicaloptions.com/hepatitis Case 1: Start Chemotherapy With Routine Monitoring of ALT, Other Labs HBV DNA Bilirubin ALT 25 3000 Chemotherapy 2500 20 HBV DNA (Log IU/mL) 2000 Bilirubin (mg/dL) 15 ALT (IU/L) 1500 10 1000 5 500 0 0 -2 0 4 8 12 16 18 20 22 24 26 Wks
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