1. Publication stage: In Press Accepted Manuscript
Combination of Tenofovir Disoproxil Fumarate and Peginterferon alfa-2a Increases Loss of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B
Patrick Marcellin, Sang Hoon Ahn, Xiaoli Ma, Florin A. Caruntu, Won Young Tak, Magdy Elkashab, Wan-Long Chuang, Seng-Gee Lim, and others
Publication stage: In Press Accepted Manuscript
Gastoenterology 30 Sep 2015
Prof. 김병호/R3 최인승

2. Introduction
Up to 400 million people worldwide are chronically infected with hepatitis B virus
Chronic infection is linked to the persistence of covalently closed circular HBV DNA within the nucleus of hepatocytes
The presence of HBsAg in the serum is a surrogate marker for cccDNA transcriptional activity
Clearance of HBsAg from the serum is associated with a functional remission of chronic hepatitis B and improved long-term outcomes

3. Introduction Standard treatment of patients with chronic Hepatitis B
Pegylated interferon-α : stimulates the natural immune response against the virus
An oral antiviral agent : suppresses replication of HBV to undetectable levels
But, HBsAg loss is uncommon with both treatment strategies(4% vs 3%)
This study compared the efficacy and safety of TDF (a potent oral nucleotide antiviral with a high barrier to resistance) and peginterferon combination therapy with TDF and peginterferon alone in patients with CHB

4. Methods Study design 4 Treatment group 18~75 years old with CHB
Mar 2011~Mar 2013
A randomized, open-label, active-controlled, multinational, superiority trial
TDF : 300 mg once daily orally
peginterferon alfa-2a : 180 μg/week, subcutaneously
4 Treatment group
A group : TDF plus peginterferon for 48 weeks
B group : TDF plus peginterferon for 16 weeks followed by 32 weeks of TDF alone
C group : TDF alone for 120 weeks
D group : peginterferon alone for 48 weeks

5. Results : Characteristics
Group A (n=186) TDF + peginterferon for 48 weeks
Group B (n=184) TDF + peginterferon for 16 weeks, then TDF for 32 weeks
Group C (n=185) TDF for 120 weeks
Group D (n=185) Peginterferon for 48 weeks
Mean age ± SD, years (range)
38 ± 16.7 (18–69)
37 ± 9.9 (18–62)
36 ± 10.9 (18–66)
38 ± 10.5 (18–64)
Body mass index Mean ± SD Range
24 ± –37
24 ± –46
25 ± –45
24± –45
Male sex – no. (%)
127 (68)
119 (65)
121 (65)
119 (64)
Race – no. (%) Asian Black* White Other
142 (76) 5 (3) 36 (19) 3 (2)
134 (73) 3 (2) 45 (25) 2 (1)
141 (76) 4 (2) 39 (21) 1 (1)
137 (74) 6 (3) 41 (22) 1 (1)
Region – no. (%) North America Europe Australia/New Zealand Asia
38 (20) 42 (23) 10 (5) 96 (52)
31 (17) 52 (28) 14 (8) 87 (47)
37 (20) 40 (22) 15 (8) 93 (50)
37 (20) 45 (24) 14 (8) 89 (48)
HBV genotype† – no. (%) A B C D E–H
17 (9) 50 (27) 78 (42) 39 (21) 2 (1)
16 (9) 51 (28) 79 (43) 36 (20) 2 (1)
14 (8) 49 (27) 78 (42) 41 (22) 3 (2)
14 (8) 53 (29) 79 (43) 38 (21) 1 (1)
HBeAg-positive – no. (%)
108 (58)
105 (57)
109 (59)
106 (57)
Mean HBV DNA, log10 IU/mL ± SD
7.1 ± 1.5
7.0 ± 1.5
6.9 ± 1.6
Mean HBsAg, log10 IU/mL ± SD
3.9 ± 0.8
3.8 ± 0.9
3.8 ± 0.8
Mean ALT, U/L ± SD
121 ± 181
112 ± 94
101 ± 68
107 ± 92
Prior HBV medication‡ – no. % Entecavir Lamivudine Clevudine Telbivudine
9 (5) 5 (3) 4 (2) 2 (1) 0
5 (3) 3 (2) 3 (2) 0 1 (0·5)
11 (6) 4 (2) 7 (4) 0 2 (1)
8 (4) 2 (1) 5 (3) 0 2 (1)

6. Results A B D C

7. TDF + peginterferon for
Group A (n=186)
TDF + peginterferon
for 48 weeks
Group B (n=184)
TDF + peginterferon for
16 weeks, then TDF for
32 weeks
Group C (n=185)
TDF for 120 weeks
Group D (n=185)
Peginterferon for
48 weeks
Week 48
Week 72
HBeAg-positive (N=428) – no./No. (%)
Overall
7/108 (6.5)
10/108 (9.3)
3/105 (2.9)
4/105 (3.8)
0/109
4/106 (3.8)
Genotype A
2/8 (25.0)
3/8 (37.5)
1/8 (12.5)
0/6
0/5
Genotype B
2/27 (7.4)
3/27 (11.1)
1/26(3.8)
0/25
2/26(7.7)
Genotype C
2/57(3.5)
3/57(5.3)
0/57
0/59
1/58(1.7)
Genotype D
1/15(6.7)
1/13(7.7)
0/17
1/16(6.3)
Genotype E-H
0/1
0/2
HBeAg-negative (N=312) – no./No. (%)
4/78(5.1)
6/78(5.1)
1/79(1.3)
0/76
2/9(22.2)
3/9(33.3)
0/8
0/9
1/23(4.3)
2/23(8.7)
1/25(4.0)
0/24
1/27(3.7)
1/21(4.8)
0/22
0/19
0/21
0/23
0/0

8. Results C B D A

9. Results : Adverse effect
Group A (n=186) TDF + peginterferon for 48 weeks
Group B (n=184) TDF + peginterferon for 16 weeks, then TDF for 32 weeks
Group C (n=185) TDF for 120 weeks
Group D (n=185) Peginterferon for 48 weeks
Any non-serious adverse event –
no. of patients (%)
145 (78)
138(75)
81(44)
150(81)
Any serious adverse event– no. of
patients (%)
21(11)
18(10)
12(7)
Discontinuation of treatment due to
adverse events – no. (%)
8(4)
4(2)
0(0)
14(8)
Patients with ALT >400 U/L (men) or >300 U/L (women), no./No. (%)
17/186(9)
17/184(9)
3/185(2)
17/185(9)

10. Conclusion
A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone.

11. Thank you for your attention