Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 10, Number 1, February 2017, pages 6-14

Antiviral Therapy in Chronic Hepatitis B With Mild Acute Exacerbation

Figure 2. The efficacy of pegIFN and NA treatments in HBeAg-positive CHB with mild AE. *P < 0.05, **P < 0.01,***P < 0.001.

**Table 1.** Annual Transition Probabilities by Initial State
Annual transitional probabilities	Estimated (%)	Range	References
HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; CHB: chronic hepatitis B; HCC: hepatocellular carcinoma.
From HBsAg clearance to			[19]
HCC	0.039
From HBeAg Positive CHB to
Spontaneous seroconversion	7.0	2.0 - 23	[18]
Compensated cirrhosis	2.4	2.1 - 2.6	[18]
HCC	0.8	0.5 - 1.0	[18]
Death	0.6	0.2 - 0.9	[18]
From HBeAg seroconversion to
HBsAg seroclearance	0.7	0.4 - 1.2	[18]
Compensated cirrhosis	1.0	0.1 - 6.3	[18]
HCC	0.2	0.05 - 0.9	[18]
From compensated cirrhosis to
Decompensated cirrhosis	3.9	3.2 - 4.6	[18]
HCC	5.0	3.0 - 7.0	[18]
Death	5.6	3.1 - 8.0	[18]
From decompensated cirrhosis to
HCC	7.1	3.5 - 10.0	[18]
Death	15	9.9 - 20.0	[18]
From HCC to
Death	54.5	20.0 - 60.0	[18]

Table 1. Annual Transition Probabilities by Initial State

Annual transitional probabilities

Estimated (%)

Range

References

HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; CHB: chronic hepatitis B; HCC: hepatocellular carcinoma.

From HBsAg clearance to

[19]

HCC

0.039

From HBeAg Positive CHB to

Spontaneous seroconversion

7.0

2.0 - 23

[18]

Compensated cirrhosis

2.4

2.1 - 2.6

[18]

HCC

0.8

0.5 - 1.0

[18]

Death

0.6

0.2 - 0.9

[18]

From HBeAg seroconversion to

HBsAg seroclearance

0.7

0.4 - 1.2

[18]

Compensated cirrhosis

1.0

0.1 - 6.3

[18]

HCC

0.2

0.05 - 0.9

[18]

From compensated cirrhosis to

Decompensated cirrhosis

3.9

3.2 - 4.6

[18]

HCC

5.0

3.0 - 7.0

[18]

Death

5.6

3.1 - 8.0

[18]

From decompensated cirrhosis to

HCC

7.1

3.5 - 10.0

[18]

Death

9.9 - 20.0

[18]

From HCC to

Death

54.5

20.0 - 60.0

[18]

**Table 2.** Annual Costs of Follow-Up or Treatment and Health State Utilities (Quality of Life) in Different Stages of Disease
	Health state costs, RMB (Dollar) [18]	Health state utilities [20]
HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; CHB: chronic hepatitis B; HCC: hepatocellular carcinoma.
HBsAg clearance	110 ($19)	0.99
HBeAg seroconversion	110 ($19)	0.95
HBeAg-positive CHB	1,162 ($170)	0.85
Compensated cirrhosis	1,514 ($222)	0.69
Decompensated cirrhosis	13,927 ($2,040)	0.35
HCC	38,795 ($5,682)	0.38

Table 2. Annual Costs of Follow-Up or Treatment and Health State Utilities (Quality of Life) in Different Stages of Disease

Health state costs, RMB (Dollar) [18]

Health state utilities [20]

HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; CHB: chronic hepatitis B; HCC: hepatocellular carcinoma.

HBsAg clearance

110 ($19)

0.99

HBeAg seroconversion

110 ($19)

0.95

HBeAg-positive CHB

1,162 ($170)

0.85

Compensated cirrhosis

1,514 ($222)

0.69

Decompensated cirrhosis

13,927 ($2,040)

0.35

HCC

38,795 ($5,682)

0.38

**Table 3.** The Baseline Characteristics and Outcomes of Acute Exacerbation Patients With Peginterferon α-2a or Nucleos(t)ide Analogues
	Peginterferon α-2a (n = 63)	Nucleos(t)ide analogues (n = 78)	P value
HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; ALT: alanine aminotransferase. *Expressed as median (interquartile range).
Baseline
Age (years)*	25 (21 - 32)	32 (26 - 35)	< 0.001
Male sex, n (%)	49/63 (77.78%)	67/78 (85.9%)	0.209
Genotype (B/C)	22:10	27:12	0.965
Biopsy
G*	3 (2 - 3)	3 (2 - 3)	0.446
S*	3 (2 - 3)	3 (2 - 3)	0.887
Duration of pretreatment (days)*	13 (7 - 17)	4 (2 - 8)	< 0.001
ALT (IU/L)*
Highest	703 (506 - 1,028)	757 (542 - 1,185)	0.348
Begin pegIFN	311 (280 - 357)
TBIL(μmol/L)
Highest	17.62 ± 5.44	19.10 ± 5.92	0.154
Begin pegIFN	13.82 ± 4.56	15.35 ± 5.68	0.110
PT(s)*	11.80 (11.40 - 12.50)	11.70 (11.40 - 12.43)	0.685
HBV DNA (log10 IU/mL)	6.87 ± 1.11	6.70 ± 0.99	0.368
HBsAg (log IU/mL)	4.20 ± 0.59	4.18 ± 0.70	0.896
HBeAg (s/co)*	740.50 (122.13 - 1,232.29)	712.14 (126.79 - 1,071.35)	0.404
Results
ALT normalization, n/total (%)
Week 12	19/63 (30.16%)	44/78 (56.41%)	0.002
Week 24	25/63 (39.68%)	60/78 (76.92%)	0.000
Week 36	34/63 (53.97%)	69/78 (88.46%)	0.004
Week 48	39/63 (61.90%)	69/78 (88.46%)	< 0.001
Week 72	45/63 (71.43%)	69/78 (88.46%)	0.011
Week 96	44/63 (69.84%)	68/78 (87.18%)	0.011
HBV DNA negative, n/total (%)
Week 12	14/63 (22.22%)	26/78 (33.33%)	0.146
Week 24	27/63 (42.86%)	47/78 (60.26%)	0.040
Week 36	36/63 (57.14%)	55/78 (70.51%)	0.099
Week 48	38/63 (60.32%)	70/78 (89.74%)	< 0.001
Week 72	36/63 (57.14%)	71/78 (91.03%)	< 0.001
Week 96	37/63 (58.73%)	71/78 (91.03%)	< 0.001
HBeAg seroconversion, n/total (%)
Week 12	6/63 (9.52%)	6/78 (7.69%)	0.698
Week 24	8/63 (12.70%)	14/78 (17.95%)	0.393
Week 36	10/63 (15.87%)	16/78 (20.51%)	0.480
Week 48	26/63 (41.27%)	24/78 (30.77%)	0.195
Week 72	29/63 (46.03%)	27/78 (34.62%)	0.168
Week 96	30/63 (47.62%)	30/78 (38.46%)	0.274
HBsAg loss, n/total (%)
Week 12	0/63 (0.00%)	0/78 (0.00%)
Week 24	0/63 (0.00%)	1/78 (1.28%)	1.000
Week 36	1/63 (1.59%)	1/78 (1.28%)	1.000
Week 48	5/63 (7.94%)	1/78 (1.28%)	0.089
Week 72	7/63 (11.11%)	1/78 (1.28%)	0.022
Week 96	9/63 (14.29%)	1/78 (1.28%)	0.005
HBsAg seroconversion, n/total (%)
Week 12	0/63 (0.00%)	None
Week 24	0/63 (0.00%)
Week 36	1/63 (1.59%)		0.447
Week 48	2/63 (3.17%)		0.198
Week 72	3/63 (4.76%)		0.087
Week 96	3/63 (4.76%)		0.087

Table 3. The Baseline Characteristics and Outcomes of Acute Exacerbation Patients With Peginterferon α-2a or Nucleos(t)ide Analogues

Peginterferon α-2a (n = 63)

Nucleos(t)ide analogues (n = 78)

P value

HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; ALT: alanine aminotransferase. *Expressed as median (interquartile range).

Baseline

Age (years)*

25 (21 - 32)

32 (26 - 35)

< 0.001

Male sex, n (%)

49/63 (77.78%)

67/78 (85.9%)

0.209

Genotype (B/C)

22:10

27:12

0.965

Biopsy

3 (2 - 3)

0.446

3 (2 - 3)

0.887

Duration of pretreatment (days)*

13 (7 - 17)

4 (2 - 8)

< 0.001

ALT (IU/L)*

Highest

703 (506 - 1,028)

757 (542 - 1,185)

0.348

Begin pegIFN

311 (280 - 357)

TBIL(μmol/L)

Highest

17.62 ± 5.44

19.10 ± 5.92

0.154

Begin pegIFN

13.82 ± 4.56

15.35 ± 5.68

0.110

PT(s)*

11.80 (11.40 - 12.50)

11.70 (11.40 - 12.43)

0.685

HBV DNA (log10 IU/mL)

6.87 ± 1.11

6.70 ± 0.99

0.368

HBsAg (log IU/mL)

4.20 ± 0.59

4.18 ± 0.70

0.896

HBeAg (s/co)*

740.50 (122.13 - 1,232.29)

712.14 (126.79 - 1,071.35)

0.404

Results

ALT normalization, n/total (%)

Week 12

19/63 (30.16%)

44/78 (56.41%)

0.002

Week 24

25/63 (39.68%)

60/78 (76.92%)

0.000

Week 36

34/63 (53.97%)

69/78 (88.46%)

0.004

Week 48

39/63 (61.90%)

69/78 (88.46%)

< 0.001

Week 72

45/63 (71.43%)

69/78 (88.46%)

0.011

Week 96

44/63 (69.84%)

68/78 (87.18%)

0.011

HBV DNA negative, n/total (%)

Week 12

14/63 (22.22%)

26/78 (33.33%)

0.146

Week 24

27/63 (42.86%)

47/78 (60.26%)

0.040

Week 36

36/63 (57.14%)

55/78 (70.51%)

0.099

Week 48

38/63 (60.32%)

70/78 (89.74%)

< 0.001

Week 72

36/63 (57.14%)

71/78 (91.03%)

< 0.001

Week 96

37/63 (58.73%)

71/78 (91.03%)

< 0.001

HBeAg seroconversion, n/total (%)

Week 12

6/63 (9.52%)

6/78 (7.69%)

0.698

Week 24

8/63 (12.70%)

14/78 (17.95%)

0.393

Week 36

10/63 (15.87%)

16/78 (20.51%)

0.480

Week 48

26/63 (41.27%)

24/78 (30.77%)

0.195

Week 72

29/63 (46.03%)

27/78 (34.62%)

0.168

Week 96

30/63 (47.62%)

30/78 (38.46%)

0.274

HBsAg loss, n/total (%)

Week 12

0/63 (0.00%)

0/78 (0.00%)

Week 24

0/63 (0.00%)

1/78 (1.28%)

1.000

Week 36

1/63 (1.59%)

1/78 (1.28%)

1.000

Week 48

5/63 (7.94%)

1/78 (1.28%)

0.089

Week 72

7/63 (11.11%)

1/78 (1.28%)

0.022

Week 96

9/63 (14.29%)

1/78 (1.28%)

0.005

HBsAg seroconversion, n/total (%)

Week 12

0/63 (0.00%)

None

Week 24

0/63 (0.00%)

Week 36

1/63 (1.59%)

0.447

Week 48

2/63 (3.17%)

0.198

Week 72

3/63 (4.76%)

0.087

Week 96

3/63 (4.76%)

0.087

**Table 4.** The Baseline Characteristics and Outcomes of Acute Exacerbation Patients With ETV or LDT Treatment
	ETV (n = 38)	LDT (n = 40)	P value
HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; ALT: alanine aminotransferase. *Expressed as median (interquartile range).
Baseline
Age (years)*	35 (20 - 39)	27 (24 - 32)	< 0.001
Male sex, n (%)	32/38 (84.21%)	35/40 (87.50%)	0.677
Genotype (B/C)	15:07	12:05	0.872
Biopsy
G*	3 (2 - 3)	3 (2 - 3)	0.719
S*	3 (2 - 3)	3 (2 - 3)	0.509
Duration of pretreatment (days)*	5 (2 - 8)	4 (2 - 7)	0.360
ALT (IU/L)*
Highest	756 (555 - 1,248)	757 (531 - 1,021)	0.803
TBIL (μmol/L)
Highest	19.07 ± 6.13	19.12 ± 5.80	0.972
PT(s)*	11.90 (11.50 - 12.50)	11.60 (11.30 - 12.38)	0.278
HBV DNA (log10 IU/mL)	6.54 ± 0.98	6.85 ± 0.99	0.168
HBsAg (log IU/mL)	4.11 ± 0.66	4.25 ± 0.75	0.454
HBeAg (s/co)	537.49 (116.81 - 1,071.12)	741.59 (184.91 - 1,102.27)	0.470
Results
ALT normalization, n/total (%)
Week 12	19/38 (50.00%)	25/40 (62.50%)	0.266
Week 24	24/38 (63.16%)	36/40 (90.00%)	0.005
Week 36	25/38 (65.79%)	35/40 (87.50%)	0.023
Week 48	33/38 (86.84%)	36/40 (90.00%)	0.734
Week 72	33/38 (86.84(%)	36/40 (90.00%)	0.734
Week 96	32/38 (84.21%)	36/40 (90.00%)	0.670
HBV DNA negative, n/total (%)
Week 12	16/38 (42.11%)	10/40 (25.00%)	0.109
Week 24	24/38 (63.16%)	23/40 (57.50%)	0.610
Week 36	27/38 (71.05%)	28/40 (70.00%)	0.919
Week 48	37/38 (97.37%)	33/40 (82.50%)	0.057
Week 72	36/38 (94.74%)	35/40 (87.50%)	0.432
Week 96	36/38 (94.74%)	35/40 (87.50%)
HBeAg seroconversion, n/total (%)
Week 12	3/38 (7.89%)	3/40 (7.50%)	1.000
Week 24	7/38 (1.84%)	7/40 (1.75%)	0.916
Week 36	7/38 (1.84%)	9/40 (22.50%)	0.656
Week 48	10/38 (26.32%)	14/40 (35.00%)	0.406
Week 72	13/38 (34.21%)	14/40 (35.00%)	0.942
Week 96	14/38 (36.84%)	16/40 (40.00%)	0.774
HBsAg loss, n/total (%)
Week 12	0/38 (0.00%)	0/40 (0.00%)
Week 24	1/38 (2.63%)	0/40 (0.00%)	0.487
Week 36	1/38 (2.63%)	0/40 (0.00%)	0.487
Week 48	1/38 (2.63%)	0/40 (0.00%)	0.487
Week 72	1/38 (2.63%)	0/40 (0.00%)	0.487
Week 96	1/38 (2.63%)	0/40 (0.00%)	0.487
HBsAg seroconversion, n/total (%)
Week 12	None	None
Week 24
Week 36
Week 48
Week 72
Week 96

Table 4. The Baseline Characteristics and Outcomes of Acute Exacerbation Patients With ETV or LDT Treatment

ETV (n = 38)

LDT (n = 40)

P value

HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B envelope antigen; ALT: alanine aminotransferase. *Expressed as median (interquartile range).

Baseline

Age (years)*

35 (20 - 39)

27 (24 - 32)

< 0.001

Male sex, n (%)

32/38 (84.21%)

35/40 (87.50%)

0.677

Genotype (B/C)

15:07

12:05

0.872

Biopsy

3 (2 - 3)

0.719

3 (2 - 3)

0.509

Duration of pretreatment (days)*

5 (2 - 8)

4 (2 - 7)

0.360

ALT (IU/L)*

Highest

756 (555 - 1,248)

757 (531 - 1,021)

0.803

TBIL (μmol/L)

Highest

19.07 ± 6.13

19.12 ± 5.80

0.972

PT(s)*

11.90 (11.50 - 12.50)

11.60 (11.30 - 12.38)

0.278

HBV DNA (log10 IU/mL)

6.54 ± 0.98

6.85 ± 0.99

0.168

HBsAg (log IU/mL)

4.11 ± 0.66

4.25 ± 0.75

0.454

HBeAg (s/co)

537.49 (116.81 - 1,071.12)

741.59 (184.91 - 1,102.27)

0.470

Results

ALT normalization, n/total (%)

Week 12

19/38 (50.00%)

25/40 (62.50%)

0.266

Week 24

24/38 (63.16%)

36/40 (90.00%)

0.005

Week 36

25/38 (65.79%)

35/40 (87.50%)

0.023

Week 48

33/38 (86.84%)

36/40 (90.00%)

0.734

Week 72

33/38 (86.84(%)

36/40 (90.00%)

0.734

Week 96

32/38 (84.21%)

36/40 (90.00%)

0.670

HBV DNA negative, n/total (%)

Week 12

16/38 (42.11%)

10/40 (25.00%)

0.109

Week 24

24/38 (63.16%)

23/40 (57.50%)

0.610

Week 36

27/38 (71.05%)

28/40 (70.00%)

0.919

Week 48

37/38 (97.37%)

33/40 (82.50%)

0.057

Week 72

36/38 (94.74%)

35/40 (87.50%)

0.432

Week 96

36/38 (94.74%)

35/40 (87.50%)

HBeAg seroconversion, n/total (%)

Week 12

3/38 (7.89%)

3/40 (7.50%)

1.000

Week 24

7/38 (1.84%)

7/40 (1.75%)

0.916

Week 36

7/38 (1.84%)

9/40 (22.50%)

0.656

Week 48

10/38 (26.32%)

14/40 (35.00%)

0.406

Week 72

13/38 (34.21%)

14/40 (35.00%)

0.942

Week 96

14/38 (36.84%)

16/40 (40.00%)

0.774

HBsAg loss, n/total (%)

Week 12

0/38 (0.00%)

0/40 (0.00%)

Week 24

1/38 (2.63%)

0/40 (0.00%)

0.487

Week 36

1/38 (2.63%)

0/40 (0.00%)

0.487

Week 48

1/38 (2.63%)

0/40 (0.00%)

0.487

Week 72

1/38 (2.63%)

0/40 (0.00%)

0.487

Week 96

1/38 (2.63%)

0/40 (0.00%)

0.487

HBsAg seroconversion, n/total (%)

Week 12

None

Week 24

Week 36

Week 48

Week 72

Week 96