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Hepatit B’de 2013 literatüründen örnekler

Hepatit B’de 2013 literatüründen örnekler. Alpay Arı İzmir Bozyaka Eğitim ve Araştırma Hastanesi. Sunum planı. Antiviral ilaçlar hepatosellüler kanser gelişimini engeller Adefovir sonrası tenofovir kullanımı güvenlidir

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Hepatit B’de 2013 literatüründen örnekler

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  1. Hepatit B’de 2013 literatüründen örnekler Alpay Arı İzmir Bozyaka Eğitim ve Araştırma Hastanesi

  2. Sunum planı • Antiviral ilaçlar hepatosellüler kanser gelişimini engeller • Adefovir sonrası tenofovir kullanımı güvenlidir • Anna Lok. Management of Chronic Hepatitis B Virus Infection in Women of Reproductive Age • Kısa, kısa

  3. Antiviral ilaçlar HCC gelişimini engeller (mi) • Morris Sherman. Hepatology 2013. • Does Hepatitis B Treatment Reduce the Incidence of Hepatocellular Carcinoma? (HCC) • Randomize kontrollü çalışma az • Bu çalışmaları yapmanın etik nedenlerle olanağı az • Cevap net değil • Metaanalizlerde genellikle retrospektif bulgular var • Bir tane lamivudinle randomize çalışma • Sonuç tartışmalı • Alınan hastaların bazılarında çalışma başladığında kanser olduğu saptanınca istatistiksel değer azalıyor.

  4. Antiviral ilaçlar HCC gelişimini engeller (mi) • Tetsuya Hosaka. Hepatology 2013 • 472 Entekavir karşı1143 eski tedavisiz yada lamivudin dirençli kurtarma yapılmamış hasta kohortu • HCC riski yüksek hastalarda etki fazla • Entekavir, lamivudinden etkili

  5. TetsuyaHosaka. Hepatology 2013

  6. TetsuyaHosaka. Hepatology 2013

  7. Antiviral ilaçlar HCC gelişimini engeller (mi) • Morris Sherman. Hepatology 2013. • Sirozlu hastalarda HCC riski antivirallerin viral replikasyonu baskılanmasıyla azalır ama kaybolmaz • Siroz olmayan hastalarda antivirallerin viral replikasyonu baskılamasıyla HCC risk azaltıcı etkinin büyüklüğü azdır • Siroz olmayan hastalarda tedavinin yeterince erken başlanması HCC riskini yok edebilir mi sorusuna cevap ne yazık ki veremeyeceğiz • Ama aktif hastalığı olanlara tedavi vermeyi kesmemeliyiz

  8. Adefovir sonrası tenofovir kullanımı güvenli (mi) dir • Thomas Berg. Gastroenterology. 2010 • Tenofovir Is Effective Alone or With Emtricitabine in Adefovir-TreatedPatients With Chronic-Hepatitis B Virus Infection

  9. Adefovir sonrası tenofovir kullanımı güvenli (mi) dir • Onur Keskin. 2013 AASLD • Response to tenofovir treatment in treatment-naive and adefovir experienced patients with hepatitis B • Adefovir direnç mutasyonu olan hastalarda cevap gecikiyor ama sonuçta HBV DNA negatifleşiyor.

  10. Adefovir sonrası tenofovir kullanımı güvenli (mi) dir • Pietro Lampertico. EASL 2013 • Tenofovir is effective for adefovir experienced patients but requires careful monitoring globuler and tubuler function and proactive dose reduction: a 4 yearstudy in 320 patients

  11. eGFR: Estimated Glomerular Filtration Rate • http://www.renal.org/egfrcalc/

  12. Adefovir sonrası tenofovir kullanımı güvenli (mi) dir • Mauro Vigano. 2013 EASL • Switching to tenofovir is safe in most chronic hepatit B patients with a reduced glomerular filtration rate due to previous exposure to adefovir dipivoxil • Adefovir + lamivudine = tenofovir + lamivudine

  13. Adefovir sonrası tenofovir kullanımı güvenli (mi) dir • Mauro Vigano. 2013 EASL • Renal function remained unchanged in most patients but carefully monitoring of GFR is mandatory to early downdoseTDF in selected patients.

  14. Anna Lok. Management of Chronic Hepatitis B Virus Infection in Women of Reproductive Age • 2013.Clinical care options

  15. Management of Chronic Hepatitis B Virus Infection in Women of Reproductive Age Anna S. F. Lok, MD Professor of Internal Medicine and Director of Clinical HepatologyUniversity of Michigan, Ann ArborAnn Arbor, Michigan This program is supported by an educational grant from

  16. Chronic HBV Infection in Women of Reproductive Age • Women who contemplate starting a family in the foreseeable future!!!!!!!!! • Women who become pregnant while receiving antiviral therapy • Women who are pregnant, have high HBV DNA, and not currently on treatment • Women with newly diagnosed HBV infection during pregnancy

  17. Antiviral Therapy for Chronic HBV Infection in Women Starting a Family in Near Future Moderate-severe inflammation; advanced fibrosis/cirrhosis? Yes No Finite treatment with pegIFN beforepregnancy* If possible,delay therapy until completion of family Treatment failure/pegIFN not possible Success Initiate NUC *Effective contraception indicated.

  18. *Eğer hasta adefovir ya da entekavir kullanıyorsa gebelik için güvenli ilaçlara değiştirme gerekmektedir. **Düşük prognoz faktörleri göze alınmalı ve transplantasyon gereksinimi olabileceği unutulmamalıdır.

  19. Women Who Become Pregnant While Receiving Antiviral Therapy Continue, switch, or stop? • Review indications for treatment • Advanced fibrosis or cirrhosis: continue • Early/mild disease or uncertain indications: stop? • Assess whether therapeutic endpoint has been reached • HBeAg seroconversion: stop? • Discuss potential risks/benefits to mother and fetus

  20. *Eğer hasta adefovir ya da entekavir kullanıyorsa gebelik için güvenli ilaçlara değiştirme gerekmektedir. **Düşük prognoz faktörleri göze alınmalı ve transplantasyon gereksinimi olabileceği unutulmamalıdır.

  21. Pregnant Women With High HBV DNA and Not Currently on Antiviral Therapy • Should antiviral therapy be recommended to reduce risk of perinatal transmission? • What should be the cutoff maternal HBV DNA level for initiation of antiviral therapy? • When to start? • Which antiviral drug? • When to stop? • What is the risk of posttreatment flares?

  22. Pregnant Women With High HBV DNA and Not Currently on Antiviral Therapy • Should antiviral be recommended to reduce risk of perinatal transmission? • Yes; although quality of evidence is low, all studies showed benefit and no harm • What should be the cutoff maternal HBV DNA level for initiation of antiviral therapy? • > 8 log10 IU/mL: Yes • 6-8 log10 IU/mL: Maybe • < 6 log10 IU/mL: No

  23. Hepatit B bebeğe ne yapar? • Yüksek HBV DNA değeri varlığında bebeği korumak için son trimester (28-32 hafta) antiviral kullanımı gerekli • Hastanın karara aktif katılımı sağlanmalı • Lamivudin, tenfovir ve telbivudin kullanılabilir • Lamivudin metaanaliz, 15 randomize kontrollü çalışma • Amaç HBV DNA değerini <106 kopya/ml indirmek* Lei H. World J Gastroenterol 2011

  24. Pregnant Women With High HBV DNA and Not Initially on Antiviral Therapy • When to stop antiviral after delivery? • To prevent perinatal transmission: immediately, especially if mother plans to breast-feed, or up to 3 mos postdelivery • To treat liver disease: continue until therapeutic endpoint • What is the risk of posttreatment flare? • Seemingly rare, but mild ALT elevation common; also seen in postpartum period for women not receiving antiviral • Decompensation not reported in clinical trials; likelihood low because most pregnant women have early-stage liver disease • Important to closely monitor ALT after antiviral therapy is discontinued (eg, 1, 3, and 6 mos posttreatment) 19. Ter Borg MJ, et al. J Viral Hepat. 2008;15:37-41.

  25. *Eğer hasta adefovir ya da entekavir kullanıyorsa gebelik için güvenli ilaçlara değiştirme gerekmektedir. **Düşük prognoz faktörleri göze alınmalı ve transplantasyon gereksinimi olabileceği unutulmamalıdır.

  26. Algorithm for HBV Management in Women During Pregnancy Pregnant women with HBV infection Active disease/suspected cirrhosis: consider initiating treatment with tenofovir 1st trimester: assess HBV replication and liver disease End of 2nd trimester: quantitative HBV DNA and ALT levels HBV DNA < 106 IU/mL* HBV DNA > 106 IU/mL* Consider initiating treatment with tenofovir, lamivudine, or telbivudine at 28-32 wks† Monitor;infant receives HBIG + vaccine at birth Infant receives HBIG + vaccine at birth *The cut-off level of maternal HBV DNA level for initiation of therapy is unclear, and HBV DNA from 6-8 log10 IU/mL can be considered for therapy based on physician and patient preference. †Tenofovir is preferred if treatment is expected to be > 12 weeks or if treatment is expected to continue while breastfeeding.

  27. Kısa kısa • Şenol Cemoğlu. 2013 • A194S mutasyonu tenofovir direnci ile ilişkili olabilir • Birlikte 233 ve 236 mutasyonu + • Tedaviye ETV eklenince A194S kaybolmuş?!

  28. Kısa kısa • J. Petersen 2013 • AASLD 2011 de 32 hastanın tedavisi kesilmiş, dokuzu hariç relaps olmuş • 9 hastaya ne olmuş???? • Hepsi Anti HBe negatif • İlaç kesildiğinde hepsinin HBsAg kantitatif değeri < 1000 IU/ml • Altısında HBsAg kaybı olmuş!!!! • Reaktivasyon yada karaciğer hastalığının derecesinde ilerleme yok

  29. HBV Reactivation With Rituximab in Pts With Hematologic Malignancies • Single-center study of HBsAg-negative anti-HBc–positive pts receiving rituximab-containing chemotherapy (N = 62) • Baseline HBV DNA undetectable (< 10 IU/mL) • No previous HBV treatment • No chronic liver disease • 24.2% of patients experienced HBV reactivation within 9 mos • Reactivation occurred early (86.7% within 6 mos) • Lower baseline anti-HBs levels associated with subsequent HBV reactivation (P = .015) Anti-HBs Levels, mIU/mL P = .015 100 ≥ 300100 - < 30010 - < 100< 10 75 Patients (%) 50 25 0 HBV Reactivation No HBV Reactivation Seto WK, et al. AASLD 2013. Abstract 34.Reproduced with permission

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