..

10 3 - 2554

99

Vol. 10 No.3

1. Immunomodulators

- Conventional interferon (intron A)
5-10 IU 3
24

- Pegylated interferon a -2a (pegasys) 180 microgram pegylated interferon
a -2b (peg-intron) 1.5 microgram
1 48

- Thymosis a 1.6 mg
2 48

2. nucleoside lamivudine
(zeffix), entecavir (baraclude), telbivudine (sebivo)

3. nucleotide adefovir
(Hepsera), tenofovir (Viread)

nucleoside
nucleotide
1 HBeAg
HBeAg HBV DNA
60 IU/ml 2 6
HBeAg
HBsAg HBV
DNA 3 6

IJM

1. (HBsAg positive) inactive
chronic hepatitis B infection (HBV carrier)

2.
serum ALT
1.5 5
500 IU/L 2
3
ALT chronic hepatitis B

3.

serum ALT 500 2,000
IU/L acute viral hepatitis
chronic hepatitis B acute flare viral
reactivation

4.
decompensation liver cirrhosis hepatitis B

5.


HIV chemotherapy

 1 HBeAg Positive chronic HBV

IJM

Vol. 10 No.3

No treatment
Interferon (IFN)
Pegylated IFN
Lamivudine (100 mg)
Adefovir (10 mg)
Tenofovir (300 mg)
Telbivudine (600 mg)
Entecavir (0.5 mg)

Loss of HBV DNA Loss of HBeAg HBeAb + Loss of HBsAg

0 17%
6 12%
4 6%
0 1%
37%
33%
18%
7 8%
25%
30 34%
21 32%
3%
40 44%
17 32%
16 21%
1%
21%
24%
12%
0%
76%

21%
3.2%
60%
26%
22%
0%
67%
22%
21%
2%

2
viral mutation

genetic resistance barrier tenofovir
entecavir
lamivudine telbivudine adefovir

. Inactive chronic hepatitis B infection (HBV

carrier) serum ALT ( < 30 IU/L
< 19 IU/L) HBeAg
positive serum ALT 3-6
HBeAg negative serum ALT

100

10 3 - 2554

6-12 1.5
.

steroid, chemotherapy, rituximab

lamivudine reactivation viral
hepatitis B hepatitis flare
12
rituximab lamivudine
1
.
. Chronic hepatitis B 2
HBeAg positive HBeAg negative

 1 HBeAg +

1. HBeAg +

HBeAg Positive
Advanced liver fibrosis
or liver cirrhosis *
Yes

No
DNA > 20,000 IU/ml
No
Yes
No treatment
Monitor DNA 6-12

Detectable HBV DNA (PCR)

Yes
No
ALT elevated

No

Consider treatment

>2 ULN
1.5 2 ULN

Liver biopsy

Vol. 10 No.3

No

Yes

IJM

No treatment
Monitor ALT, HBeAg,
DNA 3-6

Test for HBV DNA

ALT 3-6

Significant pathology **

* sign of chronic liver disease spider naevi, palmar

erythema, Gynecomastia, decompensate liver function hypoalbumin
hyperglobulin
** HAI score > 3,
ULN
= upperscdre
limit >normal
metavir
2 ULN = upper limit normal

10 3 - 2554

101

negative
HBeAg negative
2.

HBeAg
HBeAg Negative
DNA > 2,000 IU/ml
ALT Normal

DNA < 2,000 IU/ml

ALT 1.5 2 ULN

ALT > 2 ULN

Liver biopsy

No treatment
ALT , HBeAg,
HBV-DNA 6-12

No treatment
6-12

Consider
treatment

Significant pathology

No

Yes

Vol. 10 No.3

3.

IJM

Liver status
No cirrhosis

Decompensate / cirrhosis

Any of these conditions

Nucleoside or Nucleotide analogues
- Elderly
high genetic resistance barrier
- Pregnancy
Entecavir Tenofovir
- Renal insufficiency
combination Lamivudine + Adefovir
nucleotide
Severe
depression nucleoside
-
IFN Peg IFN 6--12 Anemia,
thrombocytopenia

Neutropenia
Yes
Consider Nucleotide Nucleoside

102

10 3 - 2554

No
Consider IFN Peg IFN


HbeAg positive 6-12
nucleotide nucleoside HBeAg negative 12

IFNPegIFN
Peg IFN

CBC
2

IFN

ALTadefovir
tenofovir
1-26-12

4-6

thyroid

function
test

HBV

6 HbeAg positive
6-12
HBeAg
12
DNA

3 negative

IFN ALT HBV DNA

adefovir
CBC
tenofovir

Peg IFN

ALT
2

DNA

31-2

ALT
HBV

nucleoside nucleotide

thyroid
IFN

nucleoside
nucleotide
4-6

IFN

test

HBV

function
DNA 6

4.

nucleoside
analogues
4

nucleotide
nucleotide
nucleoside
analogues
Liver cirrhosis

No liver cirrhosis

Nucleoside or Nucleotide with high genetic

barrier or combination treatment

Any approved Nucleoside or Nucleotide

depending on HBV DNA Co-morbid

IJM

Biochemical and virological response

6
Partial response
DNA 60-2,000 IU/ml

DNA >2,000 IU/ml

In adequate response

Continue treatment
6

cross
resistance* 3

Vol. 10 No.3

DNA < 60 IU/ml

Complete response

* - lamivudine adefovir tenofovir

- telbivudine adefovir tenofovir
- entecavir adefovir tenofovir
- adefovir (LAM nave) entecavir lamivudine telbivudine
- adefovir (LAM resistance) entecavir + tenofovir

10 3 - 2554

103

IJM

Vol. 10 No.3

.

2

1. Acute hepatitis B



1-3
jaundice
1-2
95-99%
seroconversion HBsAg + HBsAb +
HBsAg lamivudine 100 mg/
HBV DNA bilirubin
ALT
Acute hepatitis B

104

10 3 - 2554

fulminate liver failure prothombin time

prolong

2. Chronic hepatitis B reactivation
flare hepatitis
chemotherapy, steroid,
immunosuppressive drugs, Rituximab, anti TNFa
( rheumatoid arthritis inflammatory
bowel diseases) organ transplantation
(Bone marrow, solid organs)
ALT 3 ULN
jaundice
HBV DNA 1 log anti
HBc IgM
HBsAg positive
HBsAg negative HBV
HBV reactivation

HBV reactivation ( 5)

HBsAg +

Check DNA
Start antiviral
- Lamivudine DNA < 200
IU/ml
- Entecavir tenofovir
DNA > 2,000 IU/ml
Follow ALT, DNA
6-12
chemotherapy

HBsAg
Anti HBc +
Anti HBs HBV vaccination 1dose

HBsAg
Anti HBc +
Anti HBs +

HBsAg
Anti HBc Anti HBs -

Normal ALT

HBV vaccination
Elevate ALT

Anti HBs +

Anti HBs -

No treatment
HBV DNA +

No treatment

HBV DNA -

HBV DNA
Start Anti-viral

HBV DNA +

HBV DNA Complete HBV

vaccination

Evaluate non HBV cause

of ALT

10 3 - 2554

105

Vol. 10 No.3

HBV
reactivation
lamivudine telbivudine

HBV
reactivation

tenofovir
entecavir

Fulminant liver failure

Fulmi-

nant liver failure

.
1.

chemotherapy

immunosupressive

1. chemotherapy immunosu- agents 1. HIV
pressive agents2. lamivudine HIV antiretroviral agent (CD4

2. lamivudine ) HBV ad
efovir telbivudine cross

3. acute liver failure resistance lamivudine tenofovir
liver transplantation HIV CD4
200 cells/ml significant liver fibrosis

cirrhosis 2 lamivudine
. decompensated tenofovir anti-retroviral agents
cirrhosis IFN Peg-IFN 3 HBV DNA 400 copies/ml

IJM

5 HBV chemotherapy immunosuppressive treatment

5. HBV chemotherapy immunosuppressive treatment viral

viral reactivation
reactivation

 immune reconstitution syndrome

severe hepatitis liver failure
HBV + HIV CD4 > 500 cells/ml
peg-IFN a

2. HBV HCV
peg-IFNa HBV DNA

reactivation HBV

3.
IFN peg-IFN lamivudine telbivudine
( 2)

2 anti-HBV

Lamivudine

Telbivudine
.

CCr (ml/min)

First dose (mg)

Maintenance (mg)

30 50
15 30
5 15
<5

100
100
35
35

50
25
15
10

>50
600
600
30 49
600
600 2

<30
600
600 3
6
<5
600
600 4

First trimester

IJM

Vol. 10 No.3

6. HBV

4.
6

Check HBsAg, anti-HBc, Anti-HBs

HBsAg +

Negative for HBsAg, Anti HBs

HBV DNA at baseline wk. 28

Vaccination
Infant receive vaccination at birth

HBV DNA < 106 copies

lamivudine, tenofovir, telbivudine 32

HBV DNA > 106 copies

6 HBV
106

10 3 - 2554

IJM
Vol. 10 No.3

1.
2552 :
. http://www.liversocietythailand.
org
2. APASL Guidelines for HBV management
2008. www.apasl.info/guidelinesHBVhtml.
3. AASLD Practical Guideline : Chronic hepatitis
B update 2009. Hepatology 2009;50(3):1-35.
4. Adhish S, Rajesh K, Sajid J, Wright VK.
Chronic HBV with pregnancy : Reactivation
flare causing fulminant hepatic failure. Ann
Hepatol 2011;10(2):233-6.
5. Buti M, Brosa M, Casado MA, Rueda M,
Esteban R. Modeling the cost-effectiveness
of different oral antiviral therapies in patients
with chronic hepatitis B. Journal of Hepatology
2009;51:640-6.
6. Bruno R, Dider S. The difficulties of managing severe hepatitis B virus reactivation. Liver
international 2011:104-10.

7. Chan LYH, Jia J. Chronic hepatitis B in Asia

new insights from the past decade. Journal of
Gastroenterol and Hepatol 2010;suppl1:131-7.
8. Dusheiko GM. Cost-effectiveness of oral
treatments for chronic hepatitis B. Journal of
Hepatology 2009;51:623-5.
9. Vanagas G, Padaiga Z, Mickeviciene A. Costeffectiveness and cost-utility of the treatment
of chronic hepatitis B with peginterferon alfa2a, interferon alfa, and lamivudine in Lithuania. Medicina (Kuanas)2010;46(12):835-42.
10. Wiens A, Venson R, Januario C, Pontarolo R.
Cost-effecitveness of telbivudine vs lamivudine for chronic hepatitis B. Braz J Infect Dis
2011;15(3):225-30.
11. Wu B, Li T, Chen H, Shen J. Cost-effectiveness
of Nucleoside analog therapy for Hepatitis B in
China : A Markov Analysis. Value in Health
2010;13(5):592-60.

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