Bridging for Better Outcome

Surabaya 22 September 2012

Case Studies
Workshop 1
Advanced Knowledge to Elevate
Hepatitis B Management
Exercise

Siapakah pemenang Piala Dunia Sepakbola 2012

1. Jerman
2. Brazil
3. Spanyol 61%
61%

4. Italia

13%
13% 13%
13% 13%
13%

11 22 33 44
Case Studies 1

A 62-year-old man presented to

his primary care physician in June
of 2009 with fatigue. He gave a
history of two similar episodes of
extreme fatigue in the past five
years. During one of these Laboratory Results:
episodes, elevated liver enzymes AST: 349
were found. He did not seek ALT: 452
further attention at that time. An HBsAg: reactive
examination showed that he was Anti-HCV: non reactive
otherwise healthy. He was not on
medications, and he denied
drinking. He had no known family
history of liver disease.
The patient was referred to a gastroenterologist.
By August of 2009, when he first saw the gastroenterologist,
his symptoms had resolved. Repeat testing at this time showed
the following:
Laboratory Results:
AST : 55
ALT : 68
HBeAg : non reactive
Anti-HBe : reactive
HBV DNA : 25,000 IU/mL
What diagnosis of Hepatitis B infection is this ?

53%
53%

1. 2.
Acute HBV HBeAg
Infection negative 35%
35%

CHB

3. 4. 12%
12%

Clinically HBeAg
resolved positive 0%
0%

HBV CHB 11 22 33 44
 1. 2.
Acute HBV HBeAg
Infection negative
CHB

3. 4.
Clinically HBeAg
resolved positive
HBV CHB
Case Studies 2

• Nn.SI, 25 tahun
• Pada pemeriksaan kesehatan untuk skrining calon
karyawan didapatkan HBsAg(+)
• Selama ini tidak ada keluhan
• Belum pernah diketahui mengidap hepatitis
Pemeriksaan lanjutan
yang anda lakukan ?

1. HBeAg dan HBV DNA

2. ALT dan HBV DNA
3. ALT dan HBeAg
60%
60%

23%
23%
17%
17%

11 22 33
Pemeriksaan lanjutan
yang anda lakukan ?

1. HBeAg dan HBV DNA

2. ALT dan HBV DNA
3. ALT dan HBeAg
• Hasil pemeriksaan laboratorium
lanjutan :
- HBeAg(+)
- ALT (SGPT) 60 IU/l (Normal : 41 IU/l)
- HIV dan HCV negatif
Bagaimana sikap Anda pada pasien ini ?
A. Memberikan obat anti virus karena ALT meningkat
B. Periksa HBV DNA
C. Memantau SGPT setiap 3 bulan
67%
67%

31%
31%

3%
3%

11 22 33
Bagaimana sikap Anda pada pasien ini ?
A. Memberikan obat anti virus karena ALT meningkat
B. Periksa HBV DNA
C. Memantau ALT setiap 3 bulan
Ternyata hasil pemeriksaan HBV-
DNA memberikan hasil :
- HBV DNA 4.2 x 105 IU/ml
Bagaimana sikap Anda pada pasien ini ?
1. Memberikan obat anti virus karena SGPT
meningkat
2. Monitor HBV DNA
3. Monitor ALT 41%
41%
35%
35%

24%
24%

11 22 33
Bagaimana sikap Anda pada pasien ini ?
1. Memberikan obat anti virus karena SGPT
meningkat
2. Monitor HBV DNA
3. Monitor ALT
 HBeAg-Positive

HBV DNA >20.000 IU/ml

(>105 copies/ml)

ALT Normal ALT 1-2 x ULN

•No Treatment •No Treatment

•Monitor HBV DNA, •Monitor HBV DNA,
HBeAg, ALT/3 months HBeAg, ALT/1-3 months

•Liver Biopsy if patient is >40 years old

•Treat if moderate or greater
inflammation or fibrosis on biopsy
 Follow-Up

• Pasien tersebut dimonitor dan hasil pemeriksaan 8

bulan berikutnya :

Dalam 2 kali pemeriksaan

– ALT ~140 – 145 IU/l
– HBV DNA ulang : 4.1 x 105 IU/ml

Apakah sekarang Anda akan berikan

obat anti virus ?

17
1. Ya, obat anti virus harus diberikan
2. Belum perlu, obseravsi dilanjutkan
3. Dicoba dengan obat hepatoprotektor seperti
Sylimarin atau UDCA
91%
91%

3% 6%
6%
3%
11 22 33
1. Ya, obat anti virus harus diberikan
2. Belum perlu, obseravsi dilanjutkan
3. Dicoba dengan obat hepatoprotektor seperti
Sylimarin atau UDCA
 HBeAg-Positive

HBV DNA >20.000 IU/ml

(>105 copies/ml)

ALT 2-5 x ULN ALT >5 ULN

•Treatment if Persistent •Treatment indicated

(3-6 months) or has
concerns for hepatic
decompensation
•Interferon based therapy,
Entecavir, Telbivudine,
Lamivudine, Adefovir are
all first line options
•If HBV DNA <2 x 106 IU/mL may
choose to observe closely for 3 months
for seroconversion if no concerns for
hepatic decompensation
•Interferon based therapy, Entecavir,
Telbivudine, Lamivudine
recommended, particularly if there is
has concerns for hepatic
decompensation
Jika jawaban Anda “Ya”, obat yang Anda
berikan dan apa alasannya ?
1. Interferon, karena pasien wanita muda
2. Analog nukleosida, karena pasien wanita muda
sehingga mudah diberikan
3. Analog nukleosida karena murah
63%
63%

25%
25%
13%
13%

11 22 33
Jika jawaban Anda “Ya”, obat yang Anda
berikan dan apa alasannya ?
1. Interferon, karena pasien wanita muda
2. Analog nukleosida, karena pasien wanita muda
sehingga mudah diberikan
3. Analog nukleosida karena murah
Bagaimana memantaunya ?
1. Periksa HBsAg 3 bulan kemudian
2. Periksa HBV DNA 3 bulan kemudian
3. Periksa HBeAg 3 bulan kemudian

76%
76%

18%
18%
6%
6%

11 22 33
Bagaimana memantaunya ?
1. Periksa HBsAg 3 bulan kemudian
2. Periksa HBV DNA 3 bulan kemudian
3. Periksa HBeAg 3 bulan kemudian
 Konsep Roadmap

Mulai Terapi

Mgg12: Cek HBV DNA (penilaian kegagalan primer)

HBV DNA HBV DNA

turun > 1 log turun <1 log

Kepatuhan buruk Kepatuhan baik

Lanjutkan Konsultasi Modifikasi Terapi

Irsan Hasan
Kapan terapi bisa dihentikan ?
1. Setelah HBsAg menjadi negatif
2. Setelah HBV DNA menjadi negatif
3. Setelah HBeAg menjadi negatif dan HBV DNA
tidak terdeteksi lebih dari 12 bulan

85%
85%

12%
12%
3%
3%
11 22 33
Kapan terapi bisa dihentikan ?
1. Setelah HBsAg menjadi negatif
2. Setelah HBV DNA menjadi negatif
3. Setelah HBeAg menjadi negatif dan HBV DNA
tidak terdeteksi lebih dari 12 bulan
Case Studies 3

Patient with :
HBsAg : (+)
HBeAg : (-)
HBV DNA : Virus Detected 3,17 x 104 IU/mL

Start the treatment and after 6 month, he check and the result :
HBV DNA : Not Detected

Bridging for Better Outcome

Case Studies 3

What other parameter need to be checked ?

1. HBsAg Qual
2. HBsAg Quant
3. HBV DNA 47%
47%

4. ALT 38%
38%

9%
9%
6%
6%

11 22 33 44

Bridging for Better Outcome

Case Studies 3

What other parameter need to be checked ?

1. HBsAg Qual
2. HBsAg Quant
3. HBV DNA
4. ALT

Bridging for Better Outcome

Case Studies 3

Patient sent for HBsAg Quant and the result :

8,966 coi

What is your comment ?

Bridging for Better Outcome

Case studies 4
Patient A
40-year-old male
Diagnosed with HBeAg-positive CHB without fibrosis
ALT 3x ULN for 4 months, HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low genetic barrier)

Week 12 Week 24 Follow-up

assessment assessment 1 year

 HBV DNA 2,000  No antiviral

 HBV DNA 9,000
IU/mL resistance
IU/mL
 HBV DNA <60 IU/mL

Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-
897.
 Case studies 4
Patient A
40-year-old male 48%
48%
Diagnosed with HBeAg-positive CHB without
fibrosis 36%
36%
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low
genetic barrier) 12%
12%
4%
4%

Week 12 1. Therapy terminated 11 22 33 44

assessment
2. Partial Virologic Response and add Telbivudine
3. Partial Virologic Response and Therapy continued
 HBV DNA 9,000
IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

 Case studies 4
Patient A
40-year-old male
Diagnosed with HBeAg-positive CHB without
fibrosis
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low
genetic barrier)

Week 12 1. Therapy terminated

assessment
2. Partial Virologic Response and add Telbivudine
3. Partial Virologic Response and Therapy continued
 HBV DNA 9,000
IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

 Case studies 4
Patient A
40-year-old male 83%
83%
Diagnosed with HBeAg-positive CHB without
fibrosis
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low
genetic barrier)
8%
8%
4%
4% 4%
4%
Week 24 1. Therapy terminated 11 22 33 44
assessment
2. Partial Virologic Response and add Telbivudine
 HBV DNA 2,000 3. Partial Virologic Response and Therapy continued
IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

 Case studies 4
Patient A
40-year-old male
Diagnosed with HBeAg-positive CHB without
fibrosis
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low
genetic barrier)

Week 24 1. Therapy terminated

assessment
2. Partial Virologic Response and add Telbivudine
 HBV DNA 2,000 3. Partial Virologic Response and Therapy continued
IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

 Case studies 4
Patient A
40-year-old male 64%
64%
Diagnosed with HBeAg-positive CHB without
fibrosis
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low 20%
20%
genetic barrier) 12%
12%
4%
4%
Follow-up 1. Consider stopping therapy 11 22 33 44
1 year
2. Partial Virologic Response and add Telbivudine

 No antiviral resistance
3. Partial Virologic Response and Therapy continued
 HBV DNA <60 IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

 Case studies 4
Patient A
40-year-old male
Diagnosed with HBeAg-positive CHB without
fibrosis
ALT 3x ULN for 4 months,
HBV DNA 100,000 IU/mL
Therapy initiated with lamivudine (low
genetic barrier)

Follow-up 1. Consider stopping therapy

1 year
2. Partial Virologic Response and add Telbivudine
 No antiviral resistance 3. Partial Virologic Response and Therapy continued
 HBV DNA <60 IU/mL
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.

Bridging for Better Outcome

Case studies 5

Patient B
60-year-old female
Diagnosed with HBeAg-negative CHB with significant fibrosis
ALT 3x ULN for 3 months, HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

Week 12 Week 24 Follow-up

assessment assessment 48 weeks

 HBV DNA 900 IU/mL  HBV DNA 500 IU/mL  HBV DNA 1,000
IU/mL

Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Keeffe E.B., et al. (2007). Clin Gastro Hepatology 5,890-897.
 Case studies 5
Patient B
60-year-old female 29%
29%

Diagnosed with HBeAg-negative CHB with 25%

25% 25%
25%
21%
21%
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Week 12 11 22 33 44
assessment 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 900
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
Case studies 5
Patient B
60-year-old female
Diagnosed with HBeAg-negative CHB with
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Week 12
assessment 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 900
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
 Case studies 5
Patient B
60-year-old female 29%
29%

Diagnosed with HBeAg-negative CHB with 25%

25% 25%
25%
21%
21%
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Week 24 11 22 33 44
assessment 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 500
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
 Case studies 5
Patient B
60-year-old female
Diagnosed with HBeAg-negative CHB with
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Week 24
assessment 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 500
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
 Case studies 5
Patient B
60-year-old female 29%
29%

Diagnosed with HBeAg-negative CHB with 25%

25% 25%
25%
21%
21%
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Follow-up 11 22 33 44
48 weeks 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 1,000
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
 Case studies 5
Patient B
60-year-old female
Diagnosed with HBeAg-negative CHB with
significant fibrosis
ALT 3x ULN for 3 months,
HBV DNA 10,000 IU/mL
Therapy initiated with adefovir (suboptimal potency)

1. Therapy terminated
Follow-up
48 weeks 2. Partial Virologic Response and change to Entecavir
3. Partial Virologic Response , Therapy continued and
HBV DNA 1,000
IU/mL monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol Int
2, 263–283; Keeffe E.B., et al.
(2007). Clin Gastro Hepatology
5,890-897.
 Case studies 6
Patient C
34 year old male
Diagnosed with HBeAg-positive chronic hepatitis B with no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA and HBeAg status
monitored every 3 months

Month 3 Month 6 1-year 6-month

assessment assessment assessment follow-up

 HBV DNA 10,000  HBV DNA 1,900  HBV DNA 30 IU/mL  HBV DNA 30 IU/mL
IU/mL IU/mL  HBeAg negative
 HBeAg positive  HBeAg positive

Liaw Y-F., et al. (2008). Hepatol Int 2, 263–283; Liaw Y-F., et al. (2011). Hepatology in
press.
 Case studies 6
Patient C 29%
29%
25% 25%
34 year old male 25% 25%
21%
21%
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

Month 3 1. Therapy continued 11 22 33 44

assessment
2. Sustained Virologic Response and Therapy completed
 HBV DNA 10,000 3. Partial Virologic Response , Therapy continued and
IU/mL
 HBeAg positive monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.
 Case studies 6
Patient C
34 year old male
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

Month 3 1. Therapy continued

assessment 2. Sustained Virologic Response and Therapy completed
3. Partial Virologic Response , Therapy continued and
 HBV DNA 10,000
IU/mL
 HBeAg positive
monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.
 Case studies 6
Patient C 29%
29%
25% 25%
34 year old male 25% 25%
21%
21%
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

Month 6 1. Therapy continued 11 22 33 44

assessment
2. Sustained Virologic Response and Therapy completed
 HBV DNA 1,900 3. Partial Virologic Response , Therapy continued and
IU/mL
 HBeAg positive
monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.
 Case studies 6
Patient C
34 year old male
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

Month 6 1. Therapy continued

assessment
2. Sustained Virologic Response and Therapy completed
 HBV DNA 1,900 3. Partial Virologic Response , Therapy continued and
IU/mL
 HBeAg positive
monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.
Case studies 6
Patient C 29%
29%
25% 25%
34 year old male 25% 25%
21%
21%
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

1-year 1. Therapy continued 11 22 33 44

assessment
2. Sustained Virologic Response
 HBV DNA 30 IU/mL 3. Partial Virologic Response , Therapy continued and
 HBeAg negative
monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.
 Case studies 6
Patient C
34 year old male
Diagnosed with HBeAg-positive chronic hepatitis B with
no fibrosis
ALT 3x ULN for 4 months, HBV DNA 50,000 IU/mL
Therapy initiated with pegylated-interferon, HBV DNA
and HBeAg status monitored every 3 months

1-year 1. Therapy continued

assessment
2. Sustained Virologic Response


HBV DNA 30 IU/mL
HBeAg negative
3. Partial Virologic Response , Therapy continued and
monitor every 3 months
4. Virologic Response and Therapy continued
Liaw Y-F., et al. (2008). Hepatol
Int 2, 263–283; Liaw Y-F., et al.
(2011). Hepatology in press.