HBV??

1
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1
2
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HBV??

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Chen C-J, et al. JAMA 2006 2956573 Ganem D
Prince AM. N Eng J Med 2004 35011181129Fattovi
ch G. Semin Liver Dis 2003 234758
4
?????????????HBV-DNA??????
40
?? HBV DNA ??, ??/ml
36.2
106 (n602) 105lt106 (n333) 104lt105 (
n628) 300lt104 ( n1,150) lt300 (n869)
30
23.5
???????? (???)
20
?????????? ????????
?????? plt0.001
10
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0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
????
??????????????(N3,582)
Iloeje UH, et al. Gastroenterology.
2006130678-86.
5
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?????? HCC, ????? ???
25
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21
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15
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Liaw Y-F, et al. NEJM 2004 3511521-1531
6
????????????????????
???? ?????? ???????
2008??????? ???? HBV DNAgt2000IU/mL (104??/??) HBV DNA??
2009??????? ?? HBV DNAgt2000IU/mL??lt2000IU/mL??ALT?? HBV DNA??
2009??????? ?? HBV DNA?? ?????
2010??????????? ??ALT????,HBeAg???HBV DNAgt104 ??/??HBeAg???HBV DNAgt103??/???HBV???,???????????,????????????????? ????HBV DNA,??ALT?AST????,??????????,??????(?)????????

• E.B. Keeffe, et al Clinical Gastroenterology and
  Hepatology 23 Aug 2008 available on line
• EASL Clinical Practice Guideline Management of
  CHB, J Hepatol 50 (2009),doi10.1016/j.jhep.2008.1
  0.001
• http//www.aasld.org/practiceguidelines/Pages/defa
  ult.aspx
• ???????,2011? ?27?,?1?,??????????(2010??)

7
??????????????????

• 2008???????????
• ??????HBV DNA???HBsAg??
• 2009?????????
• ????????????????HBeAg????????HBeAg????????6??????
  ,HBeAg??????HBsAg??????????
• ?????????????
• 2009?????????
• ???????????
• ????????????(2010??)
• ??????????????,?????????????(?)?????,?????????
• ??????????????,?????????????(?)?????,?????????,??
  ?????

• E.B. Keeffe, et al Clinical Gastroenterology and
  Hepatology 23 Aug 2008 available on line
• EASL Clinical Practice Guideline Management of
  CHB, J Hepatol 50 (2009),doi10.1016/j.jhep.2008.1
  0.001
• http//www.aasld.org/practiceguidelines/Pages/defa
  ult.aspx
• ???????,2011? ?27?,?1?,??????????(2010??)

8
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9
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10
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• ????????????HCC???
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1. ???????,2011? ?27?,?1?,??????????(2010??)

11
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• ????????????????????
• ???,????????????
• ??????,????????,????????
• ?????????
• ?????????????????

12
?????????48???HBV DNA????6.9 log10
????
????
????
????
0
-3.6
-6.9
-6.5
-5.4
-2
-4
HBV DNA (log10 ??/??)
-6
-8
HBeAg??????????
TT Chang et al. N Engl J Med 2006 354
1001-10 Lai CL et al. Shanghai-Hong Kong
International Liver Congress March 25-28, 2006.
Poster 182 Marcellin et al. N Engl J Med 2003
348808-16
13
?????????,??? ???????????
Ju Hyun Shim, Han Chu Lee, Kang Mo Kim,
Young-Suk Lim, Young-Hwa Chung, Yung Sang
Lee, Dong Jin Suh, Journal of Hepatology 2010
vol. 52 j 176182,
14
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15
????????????????????????????

• ?????,??????????HBV???
• ????????
• ??????ALT????????
• ????????,?????????
• ?????
• ????????????
• ?????????

Locarini SA, Seminar in liver disease. 2006,
26163
16
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LVD1

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11
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0
29

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0
0
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1.2
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?72??HBV DNA 400 copies/mL??????TDF??????FTC??
,72??????????TDF?????????5,6 ??????? ??HBeAg
() ?? HBeAg(-) N/A ????
1. Locarnini S. Hepatol Int. 20082147-51. 2.
Lai CL, et al. N Engl J Med, 20073572576-8 3.
Liaw YF, et al. Gastroenterology 2009136486-95.
4. Snow-Lampart A, et al. AASLD Oct 31Nov 4,
2008, San Francisco, USA. Oral Presentation 977
Hepatology 200848745A. 5. D.J. Tenney, et al
ENTECAVIR MAINTAINS A HIGH GENETIC BARRIER TO HBV
RESISTANCE THROUGH 6 YEARS IN NAIVE PATIENTS EASL
2009 annual meeting Abstract 20. 6. Tenney et
al. EASL April 2226, 2009, Copenhagen, Denmark,
Oral Presentation 1761.
17
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???? ??,???? ????????? ?12????? ???
???? ????,??????? ?
???? ??????,9??????????3/4???,???? ?
?????12???????????1224?????HBV DNA??
?HBeAg-??,??????24?????HBeAg/?-HBe
Lok A McMahon B. Hepatology.200950136 Tyzeka
US PI, (available at http//www.accessdata.fda.gov
/scripts/cder/drugsatfda/index.cfm).cv
19
???????????????? ??????????
???????????? ????
190 ???
????
??? HBV DNA lt12 IU/mL() p
?? (n116) 84 0.024
??(n60) 87 0.024
????(n14) 57 0.024
14 (7)
116 (61)
60 (32)
?????
?????
Sogni P, et al. 45th EASL, Apr 14 Apr 18, 2010,
Vienna, Austria. Poster presentation 1023.
(Journal of Hepatology 201052(suppl)S395).
20
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21
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144 ? (24 ?) (24 ?)
Liaw Y-F, et al. 59thAASLD meeting Oct 31 Nov
4, 2008, San Francisco, USA. Poster
894.Hepatology.200848706A.
23
????????????????

• ??????
• ETV-901??????
• ETV????3?
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• ?ETV-022?ETV-027???,???? ETV??0.5 mg ??
• ?ETV-901???,????????,??????ETV??1.0 mg??

Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
24
??????III??????????????
ETV-022 ?? HBeAg(), (N354) ETV-027 ?? HBeAg(-), (N325) ????? ??
???() 41 (72) 16 (28) 57
???? (?) 35 44 40
?? () ?? ??() ???() 77 58 42 7638 62 826733
HBV DNA??,?? (log10 ??/mL) 9.62 7.60 9.40
ALT, ?? (U/L) 140 141 142
HBV??? ()

A
B
C
D
??
Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
25
?????????????????? (n57)
60
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240 (5?)
288 (6?)
336 (7?)
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Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
26
????1???3-7??Knodell ?????????
60
Knodell ??????
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0
??
?48?
??
Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
27
??????297??????Knodell ??????
A
B
D
C
Images reproduced with the kind permission of
Prof Z Goodman (Patient 10257)
28
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?48?
??
Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
29
????????/?????Ishak ???????
????
48 ???
????(??? 6 ?)
Ishak ?????
??
??????????
? ????????
Adapted from Chang TT, et al. 19thAPASL meeting,
February 1316, 2009, Hong Kong, China. Poster
PE119. BMS Data on file.
30
????????????????,????????
?? Ishak ?????6
? 1? Ishak ?????6
? 5? Ishak?????2
Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
31
??????????????(88)???Ishak?????????
Ishak ????????? ( ??1? )
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80
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??
Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
32
?????????????

• ????????????????????
• ???57????HBV DNA(lt300 ??/mL)????
• 95???Knodell????????0-3??
• 88???Ishak?????????
• 75???Knodell??????0?1
• ??????????/??????(Ishak ????? 4) ?????????

Chang TT, et al. Long-term entecavir therapy
results in reversal of fibrosis/cirrhosis and
continued histological improvement in chronic
hepatitis B patients. Hepatology. Manuscript
submitted.
33
??????????????????????????????????
?? ??????? ???????
?? ?????? ???????
2008??????????? ????????? ????????? ????
2009??????? ?? ????????? ??????????????(????)????(????)
2009??????? ?? ????????? ?????????
2010???????????? ??????? ??(?)??? ??????? ??(?)???

• E.B. Keeffe, et al Clinical Gastroenterology and
  Hepatology 23 Aug 2008 available on line
• EASL Clinical Practice Guideline Management of
  CHB, J Hepatol 50 (2009),doi10.1016/j.jhep.2008.1
  0.001
• http//www.aasld.org/practiceguidelines/Pages/defa
  ult.aspx
• ???????,2011? ?27?,?1?,??????????(2010??)

34
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• ????????????????,?????????????????????
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35
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36
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37
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• 4 ?? (??, gt50 ??)
• C? ?????????????????
• 0 ?
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• 2 2-4???
• 3 5-10???
• 4 10???

• B? ?????
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• 1 ???????
• 2 ??????3??????
• 3 ??????3??????
• 4 3?????? ?????-????????
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• D? ?????
• 0 ?
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• 4 ??, ?????

Iskak KG, et al., J Hepatol. 199522696-9.
38
Ishak????

• Ishak ??????????????????
• ????????
• Ishak???2.3 1.27,??????????????????????

?? Ishak ??
0 ????
1 ??????????
2 ??????????
3 ?????????? ?????
4 ??????? (P-P?P-C)
5 ???????(P-P?/?P-C), ?????(???????)
6 ?????????
P-P??????? P-C????????
Ishak KG, et al., J Hepatol. 199522696.