慢性B型肝炎治療的今日觀 - tma.tw

1 B 2009 EASL B hepatitis B virus, HBV B HBV 1,2 2007 2009 American Association for the Study of Liver Diseases, AASLD European Association for the Study o f t h e L i v e r, E A S L ( A s i a n Pacific Association for the Study of the Liver, APASL 2 0 0 9 4 22-26 Bella Center 44 EASL B clinical practice guideline B B B B 5 cumulative incidence 8-20% 5 20% 5 80-86% 5 14-35% B 2-5% 3-6 B goal of therapy B 1 3-6 B B B B B)

2 HBV DNA B H B V H B V interferon nucleoside/nucleotide analogue, NUC HBV B i n t e r f e r o n , I N F - p e g y l a t e d i n t e r f e r o n , p e g I N F - H B V L - L - n u c l e o s i d e s l a m i v u d i n e ( ) telbivudine( ) emtricitabine (deoxyguanosine analogues) entecavir ( ) acyclic nucleoside phosphonate adeofovir( ) tenofovir (FDA)

3 2 3 adefovir tenofovir t e l b i v u d i n e H B V D N A genetic barrier to resistance 24 lamivudine monotherapires B end-points of therapy 3-6 B 507508262009, , B B 6 1 2 HBV 4 H B V H B V DNA 9 PCR 10-15 IU/mL ALT HBV DNA HBeAg HBeAg HBeAg HBsAg 5 H B e Ag HBeAg end-point HBeAg HBeAg ALT 3 HBV DNA 2 106 IU/mL 107 copies/mL (3)

4 1 B 3-6 2 FDA B 1 2007 AASLD B HBV 2008 APASL B HBV B HBV DNA ALT (HCC 2009 EASL HCC HBV HCC HBV cccDNA HBV interferon -2bIntron A 1991lamivudine(LVD)Epivir-HBV Zeffix(Asia) 1998adefovir dipivoxil(ADV)Hepsera 2002entecavir(ETV)Baraclude 2005pegylated interferon -2aPegasys 2005telbivudine(TLV Ldt))

5 Sebivo 2006 AASLD American Association for the Study of Liver Diseases APASL Asian Pacific Association for the Study of the Liver EASL European Association for the Study of the Liver 507508272009, , 3 1,3 4 B 3-6 interferon -2b HBsAg HBeAg 65-70% lamivudine 8 Hepsera 7 9 . 1 - 2 0 % 4-5 70% HBV DNA adefovir LVD ETV 0% 2% 7% 15% 30% LVD ETVentecavir LVD ADV LVD (HBV- na ve) 4 LVD ETV> ADV>TLV>LVDpegylated interferon -2a 65-70% telbivudine HBeAg( ) HBeAg( )

6 LVD 2007 AASLD HBeAg 50-90% HBeAg HBV DNA PCR HBeAg 2008 APASLHBeAg HBeAg 6 PCR 2 HBV DNA HBeAg 2009 EASLHBeAg HBsAg anti-HBs B HBeAg HBeAg HBeAg HBeAg HBeAg ( ) HBV DNA 509510282009, , H B e A g 12 HBV DNA RT-PCR HBV DN HBeAg HBeAg 24-48 HBeAg HBsAg HBsAg 3 EASL B 2009 EASL B HBeAg 1 2 1 lamivudine(LAM) adefovir (ADV) entecavir (ETV) telbivudine (LdT) tenofovir (TDF)

7 1 24% 36-39% 21% 67% 60% 74% HBeAg 30% 20% H B e A g 1 HBsAg 3-4% lamivudine adefovir entecavir telbivudine tenofovir 3% 2 L A M A D V ETV LdT TDF 63% 72% 5 1 % 9 0 % 8 8 % 9 1 % 1 H B s A g 3 % l a m i v u d i n e a d e f o v i r 5 B 3-6 HBeAgHBV DNAALT IU/mL 2 ULN l a m i v u d i n e adeofovir telbivudine entecavir INF- /pegINF- ALT 3 6 HCC IU/mL 2 ULN INF- lamivudine adeofovir telbivudine entecavir INF- /pegINF- lamivudine entecavir IU/mL 2 ULN INF- /pegINF- lamivudine adeofovir entecavir lamivudine adeofovir entecavir IU/mL1-2 ULN ALT HIBV DNA HBV HCC ALT lamivudine adeofovir entecavir INF- /pegINF- ALT 3 6 HCC ULN / IU/mL (5)

8 Lamivudine adeofovir entecavir lamivudine adeofovir entecavir INF- /pegINF- / IU/mL 3 6 HCC ULN INF interferon 509510292009, , entecavir telbivudine tenofovir HBV DNA head-to-head comparisons 1 2 EASL B broad dynamic range real-time polymerase chain reaction, RT-PCR combined therapy 3 B H B e A g B HBV DNA 104 IU/mL(105 copies/mL) HBeAg ALT HBeAg HBV DNA 103 IU/mL (104 copies/m L ) A LT 5 HBV DNA H B V immune tolerant phase immune reactive phase HBV inactive HBV carrier state HBeAg (HBeAg-negative CHB)

9 B (HBsAg-negative phase) sequential HBV HBV HBV HBeAg ALT AST 50-70% B 5-10 1 HBeAg (3) 2 HBeAg (3)511512302009, , H B e A g HBeAg HBV HBV DNA 104 copies/mL( 103 IU/mL) ALT ALT AST HBV DNA HBeAg ALT B HBV 10 H B V H B e A g HBe HBV DNA 105 copies/mL ALT HBsAg B C C HBeAg B HBeAg ALT AST HBV DNA 105 copies/mL H

10 B e A g HBV DNA 104 -108 copies/mL ALT B HBV DNA -fetoprotein, AFP B