B型肝炎治療新知
台大醫院內科部
陳健弘
B型肝炎的
流行病學
2010-8-11 苗栗
Chen CH
台灣成人每五人中，就有一人
是B型肝炎帶原者，全國約有
300萬(20%) B型肝炎帶原者
每5人就有1人
有B型肝炎
2010-8-11 苗栗
Chen CH
B型肝炎帶原率
25%
20%
15%
10%
5%
0%
20-29
30-39
40-49
50-59
60-69
70-79
80-89
>=90
20 years after
mass HBV
vaccination
 Year 2004
 17,637 healthy individuals (M/F,
9785:7852), <20 y/o
 1142 individuals (M/F, 693:449) aged
between 20 and 30 years
 from schools, institutes, or workplaces
in Taipei City,
HBsAg(+): 1.2%
HBV vaccination
reduce HCC
incidence
group
Person-years
No. of
HCC
nonvaccinated
78,496,404
444
1(reference)
vaccinated
37,709,340
64
0.31 (0.24 to 0.41)
RR(95% CI)
P<0.001
Natural course of CHB
Natural course of CHB
Liaw YF and Chu CM. Lancet 2009; 373: 582–92
HBV DNA
 IU/mL
 copies/mL
 pg/mL
REVEAL-HBV
Risk Evaluation of Viral Load
Elevation and Associated Liver
Disease/Cancer– Hepatitis B Virus
HBV DNA as a
risk for cirrhosis
HBV DNA Associated With
Increased Risk of Liver cirrhosis
REVEAL: Long-term follow-up of untreated HBsAg positive individuals in Taiwan
Cumulative Incidence of cirrhosis at Year 13 Follow-up[1] (N = 3582)
Patients (%)
50
40
36.2
30
23.5
20
10
9.8
4.5
5.9
0
< 300
100,000- ≥ 1 million
30010,000999,999
9999
99,999
Baseline HBV DNA (copies/mL)
ILOEJE UH et al., GASTROENTEROLOGY 2006;130:678–686
HBV DNA as a
risk for HCC
HBV DNA Associated With
Increased Risk of HCC
REVEAL: Long-term follow-up of untreated HBsAg positive individuals in Taiwan
Cumulative Incidence of HCC at Year 13 Follow-up[1] (N = 3653)
14.9
15
Patients (%)
12.2
12
Median age: 45
HBeAg(-): 85%
ALT<45:94%
9
6
3.6
3
1.3
1.4
0
< 300
300100010,000≥ 100,000
999
9999
99,999
Baseline HBV DNA (copies/mL)
Chen CJ et al., JAMA. 2006;295:65-73
Risks of HCC
in HBV carriers
Risk factors associated with HCC in HBV carriers









Male
Increasing age
High ALT level
Alcohol consumption
HBeAg (+)
High HBV DNA
Genotype C
Presence of cirrhosis
….
AUC: 0.851
AUC: 0.852
Yang HI et al., J Clin Oncol 2010;28:2437-2444
Initial evaluation
當病人說他有B肝時，必須
釐清是否是HBsAg(+)，如
果無書面資料，建議check
HBsAg來證實
HBsAg
HBeAg
AST, ALT, AFP
Ultrasound
慢性B型肝炎
e抗原陽性慢性B型肝炎
e抗原陰性慢性B型肝炎
B肝病人，
誰需要治療？
案例
21歲男性
HBsAg(+)，ALT: 24 U/L，HBeAg(-) HBV
DNA: 100 IU/mL，
上網找到資料，B肝帶原者日後得到肝癌
的機會較大。
問題︰要不要治療以便終止帶原狀態？
Inactive HBsAg carrier
25. In patients with inactive HBsAg
carrier state antiviral treatment is
not indicated, but these patients
should be monitored (see
Recommendation 12). (II-2)
Hepatology 2009 AASLD practice guideline CH-B
案例
21歲男性，
HBsAg(+)，ALT: 60 U/L， HBeAg(+)
HBV DNA: 3x109 IU/mL，上網找到資料，
HBV DNA愈高則日後得到肝癌的機會愈
大。
問題︰要不要治療？
HBeAg(+) CH-B
15b. ALT persistently normal or <2 X ULN.
These patients generally should not be
initiated on treatment. (I)
 Liver biopsy may be considered in patients with
fluctuating or minimally elevated ALT levels
especially in those above 40 years of age. (II-3)
 Treatment may be initiated if there is moderate
or severe necroinflammation or significant
fibrosis on liver biopsy. (I)
Hepatology 2009 AASLD practice guideline CH-B
案例
25歲男性
HBsAg(+)
ALT: 150 U/L
HBeAg(+)
HBV DNA: 3x109 IU/mL
問題︰要不要治療？
HBeAg(+) CH-B
15a. ALT ≧ 2 x ULN or moderate/severe
hepatitis on biopsy, and HBV DNA
>20,000 IU/ml. These patients should be
considered for treatment. (I)
Hepatology 2009 AASLD practice guideline CH-B
案例
40歲男性
HBsAg(+)
ALT: 150 U/L
HBeAg(-)
HBV DNA: 7x106 IU/mL
問題︰要不要治療？
HBeAg(-) CH-B
16. Patients with HBeAg(-) chronic
hepatitis B (serum HBV DNA >20,000
IU/ml and elevated ALT>2 x ULN) should
be considered for treatment.(I)
APASL: HBV DNA > 2000 IU/mL
Hepatology 2009 AASLD practice guideline CH-B
案例
45歲男性
HBsAg(+)
ALT: 50 U/L
HBeAg(-)
HBV DNA: 3x103 IU/mL
超音波: liver cirrhosis + splenomegaly
問題︰要不要治療？
Compensated liver cirrhosis
23. Patients with compensated
cirrhosis — Treatment should be
considered for patients with ALT >2 UNL,
and for patients with normal or minimally
elevated ALT if serum HBV DNA levels
are high (>2,000 IU/ml). (II-2)
 Patients with compensated cirrhosis are best treated
with NAs because of the risk of hepatic decompensation
associated with IFNa–related flares of hepatitis. In view
of the need for long-term therapy, tenofovir or entecavir
is preferred. (II-3)
建議轉給 hepatologist
Hepatology 2009 AASLD practice guideline CH-B
案例
45歲男性
HBsAg(+)
ALT: 50 U/L, Bilirubin: 5 mg/dL
HBeAg(-)
HBV DNA: 3x103 IU/mL
超音波: liver cirrhosis + splenomegaly +
massive ascites
問題︰要不要治療？
Decompensated liver cirrhosis
24.
Patients
with
decompensated
cirrhosis - Treatment should be promptly
initiated with a NA that can produce rapid
viral suppression with low risk of drug
resistance. (II-1)
盡快轉給 hepatologist
Hepatology 2009 AASLD practice guideline CH-B
治療B型肝炎的藥物
 傳統型干擾素
 長效型干擾素
 干安能 (lamivudine, Zeffix)
 干適能 (adefovir, Hepsera)
 貝樂克 (entecavir, Baraclude)
 喜必福 (telbivudine, Sebivo)
 tenofovir
要治療多久
案例
25歲男性 HBsAg(+), ALT: 150 U/L,
HBeAg(+), HBV DNA: 3x109 IU/mL
使用抗病毒藥治療1年後
ALT: 30 U/L, HBeAg(+)
HBV DNA: 測不到
問題︰可不可以停藥？
Duration of nucleoside analogue
treatment- HBeAg(+)
32a. HBeAg(+) chronic hepatitis B —
Treatment should be continued until
the patient has achieved HBeAg
seroconversion and completed at
least 6 months of additional
treatment after appearance of antiHBe. (I)
 Close monitoring for relapse is needed after withdrawal
of treatment. (I)
Hepatology 2009 AASLD practice guideline CH-B
案例
40歲男性
HBsAg(+), ALT: 150 U/L, HBeAg(-)
HBV DNA: 7x106 IU/mL
使用抗病毒藥治療1年後
ALT: 30 U/L, HBV DNA: 300 IU/mL
治療2年後
ALT: 30 U/L, HBV DNA: 測不到
問題︰可不可以停藥？
Duration of nucleoside analogue
treatment- HBeAg(-)
32b. HBeAg(-) chronic hepatitis B —
Treatment should be continued until
the patient has achieved HBsAg
clearance. (I)
在亞太地區，做不到
Hepatology 2009 AASLD practice guideline CH-B
Recommendation 9 (II)
For oral antiviral agents:
In HBeAg-negative patients, it is not
clear how long this treatment should be
continued, but treatment discontinuation
can be considered if undetectable
HBV-DNA has been documented on three
separate occasions 6 months apart. (II).
2008 APASL consensus statement
案例
45歲男性
HBsAg(+), ALT: 50 U/L, HBeAg(-)
HBV DNA: 3x103 IU/mL
超音波: liver cirrhosis + splenomegaly
使用抗病毒藥治療1年後
ALT: 30 U/L, HBV DNA: 測不到
治療3年後
ALT: 32 U/L, HBV DNA: 測不到
問題︰需要繼續用藥嗎？健保給付嗎？
Duration of nucleoside analogue
treatment- Compensated cirrhosis
32c. Compensated cirrhosis —
These patients should receive long-term
treatment. However, treatment may be
stopped in HBeAg(+) patients if they
have confirmed HBeAg seroconversion
and have completed at least 6 months of
consolidation therapy and in HBeAg(-)
patients if they have confirmed HBsAg
clearance. (II-3)
 Close monitoring for viral relapse and hepatitis flare is
mandatory if treatment is stopped. (II-3)
Hepatology 2009 AASLD practice guideline CH-B
Duration of nucleoside analogue
treatment- Decompensated cirrhosis
32d. Decompensated cirrhosis and
recurrent hepatitis B post-liver
transplantation - Life-long treatment
is recommended. (II-3)
Hepatology 2009 AASLD practice guideline CH-B
特殊族群
案例
45歲男性
HBsAg(+), ALT: 20 U/L, HBeAg(-)
HBV DNA:測不到
惡性淋巴瘤，準備做化學治療
問題︰要不要治療？
Treatment of Hepatitis B carriers Who Require
Immunosuppressive or Cytotoxic Therapy
39. HBsAg testing should be performed
in patients who are at high risk of HBV
infection (see recommendation number
1), prior to initiation of chemotherapy or
immunosuppressive therapy. (II-3)
Hepatology 2009 AASLD practice guideline CH-B
Treatment of Hepatitis B carriers Who Require
Immunosuppressive or Cytotoxic Therapy
40. Prophylactic antiviral therapy is
recommended for HBV carriers at the
onset of cancer chemotherapy or of a
finite course of immunosuppressive
therapy.
Hepatology 2009 AASLD practice guideline CH-B
啊﹗治療B肝這麼複雜，我
已經搞混了，誰記得住這
些guideline？怎麼辦？
可以將病人轉給 hepatologist
全民健康保險加強
慢性B、C型肝炎
治療試辦計畫
全民健康保險加強慢性B、C型肝炎治療試辦計畫
e(+) CHB
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
HBsAg (+) > 6個月
HBeAg (+) >3個月
ALT ≧ 5X
無肝功能代償不全
2X≦ ALT ＜ 5X
且 HBV-DNA ≧ 20,000 IU/mL
or 肝組織切片HBcAg(+)
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg) 12-36個月
IFN / Pegasys 6個月
IF HBeAg (+) Tx 36個月內，有e抗原陰轉者，
則可再给付最多12個月治療
全民健康保險加強慢性B、C型肝炎治療試辦計畫
e(-) CHB
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
HBsAg (+) > 6個月
HBeAg (-) >3個月
半年內2次以上ALT ≧2X (每次間隔3個月),
且HBV-DNA≧2,000 IU/mL
or 肝組織切片HBcAg(+)
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg) 12-36個月
IFN / Pegasys 6個月
全民健康保險加強慢性B、C型肝炎治療試辦計畫
CHB
decompensation
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
已發生肝代償不全
(PT ≧ 3秒 or Bil ≧ 2mg/dl)
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg) 12-36個月
IF HBeAg (+) Tx 36個月內，有e抗原陰轉者，
則可再给付最多12個月治療
全民健康保險加強慢性B、C型肝炎治療試辦計畫
化療及移植
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
1.接受非肝臟之器官移植後，B型肝炎發作者
2.接受癌症化學治療中，B型肝炎者發作者,經照會
消化系專科醫師同意後
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg)
長期使用
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
1. 接受肝臟移植者,可預防性使用
2. 接受癌症化學治療,經消化系專科醫師同意後,可於
化療前一週開始給付使用,直至化療結束後6個月,以
預防B肝發作
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg)
全民健康保險加強慢性B、C型肝炎治療試辦計畫
肝硬化篇
全民健康保險加強慢性B、C型肝炎治療試辦計畫
HBsAg(+)
肝硬化病患
(1) HBsAg (+)且血清HBV DNA≧2,000IU/mL
+
(2) 肝組織切片（Metavir F4或Ishak F5以上)
or
超音波診斷為肝硬化併食道或胃靜脈曲張
or
超音波診斷為肝硬化併脾腫大
可長期使用
Zeffix(100mg) / Sebivo(600mg) / Baraclude(0.5mg)
全民健康保險加強慢性B、C型肝炎治療試辦計畫
抗藥性篇
全民健康保險加強慢性B、C型肝炎治療試辦計畫
使用口服抗病毒藥 出現抗藥性病毒株
(指治療中HBV-DNA從治療期間之最低值上
升超過 1 log IU/mL)
1. Add on Adefovir →36個月
2. 改用Baraclude(1mg)僅限干安能抗藥性 →36個月
3. IFN or Pegasys →12個月
若停藥後復發，得以合併療法再治療一次，
療程為3年；或以干擾素再治療1年
Note: B型肝炎抗藥株復發療程定義為：治療完成時，血
中偵測不到病毒，停藥後血中病毒又再次偵測到。
健保相關
Q︰nephrotic syndrome或
是autoimmune disease
的HBsAg(+)病人使用
steroid，需要prophylaxis
嗎？
Q︰標靶治療是
chemotherapy嗎？
Q:已經開藥了，但
chemotherapy因故
延後，會被核刪嗎？
財團法人
肝病防治學術基金會
http://www.liver.org.tw/
服務時間：
週一至週日
上午8:30～晚上9:00
為什麼
他可以健保用藥，
我卻不行？
案例
今早接獲一民眾來電，已吃貝樂克2年半
了，現今仍繼續治療中，但都自費領藥。
問題1—可否用健保來領藥（GPT已降至40
左右，病毒量仍有約10的4次方）
問題2—能否停藥？因長期自費治療已花了
很多錢
為什麼不能入健保用藥
沒有表面抗原資料
沒有e抗原資料
沒有HBV DNA資料
用藥資訊不清楚
我有B肝的病人
需要治療，我要
轉診給誰？
Thanks
chenhcc@ntuh.gov.tw