Appendix 1: Pooled analysis used to calculate number needed to treat (1/pooled absolute risk difference) and number of attributable per 1000 events (1000*pooled absolute risk difference)
Comparison / Author, year / Activen/N / Control
n/N / Active
weeks of treatment/ followup / Control
weeks of treatment/
followup / RR (95% CI) / Absolute Risk Difference
95% CI / Weight, % /
HBeAg loss
Adefovir 10 vs. placebo / Marcellin, 2003 (1) / 41/171 / 17/167 / 48/0 / 48/0 / 2.4(1.4;4.0) / 0.14 / 0.06 / 0.22 / 24.44
Zeng, 2006 (2) / 24/120 / 10/120 / 52/0 / 52/0 / 2.4(1.2;4.8) / 0.12 / 0.03 / 0.20 / 21.87
Zeng, 2006 (2) / 30/240 / 10/120 / 52/0 / 52/0 / 1.5(0.8;3.0) / 0.04 / -0.02 / 0.11 / 29.49
Adefovir 30 vs. placebo / Marcellin, 2003 (1) / 44/173 / 17/167 / 48/0 / 48/0 / 2.5(1.5;4.2) / 0.15 / 0.07 / 0.23 / 24.2
Pooled / 0.11 / 0.06 / 0.16 / 100
Heterogeneity / p = 0.122 / I-squared / 0.48
Adefovir + vs. lamivudine / Perrillo, 2004 (3) / 6/46 / 1/49 / 52/0 / 52/0 / 6.4(0.8;51.1) / 0.11 / 0.01 / 0.22 / 73.16
Peters, 2004 (4) / 3/20 / 0/19 / 48/0 / 48/0 / 6.7(0.4;121.1) / 0.15 / -0.02 / 0.32 / 26.84
Pooled / 0.12 / 0.03 / 0.21 / 100
Heterogeneity / p = 0.699 / I-squared / 0.00
Lamivudine vs. placebo / Dienstag, 1999 (5) / 21/71 / 8/72 / 52/0 / 52/0 / 2.7(1.3;5.6) / 0.19 / 0.06 / 0.31 / 19.85
Yao, 1999 (6) / 23/322 / 5/107 / 12/0 / 12/0 / 1.5(0.6;3.9) / 0.03 / -0.02 / 0.07 / 30.27
Perrillo, 2002 (7) / 102/406 / 20/196 / 52/0 / 52/0 / 2.5(1.6;3.9) / 0.15 / 0.09 / 0.21 / 29
Schiff, 2003 (8) / 38/119 / 7/56 / 52/0 / 52/0 / 2.6(1.2;5.4) / 0.19 / 0.07 / 0.32 / 20.88
Pooled / 0.13 / 0.04 / 0.22 / 100
Heterogeneity / p = 0.001 / I-squared / 0.81
Interferon Alfa 2b vs. no treatment / Di Bisceglie, 1993 (9) / 11/25 / 1/22 / 16/8 / 16/8 / 9.7(1.4;69.1) / 0.40 / 0.18 / 0.61 / 32.1
Waked, 1990 (10) / 13/20 / 5/20 / 16/48 / 16/64 / 2.6(1.1;5.9) / 0.40 / 0.12 / 0.68 / 25.94
Perrillo, 2002 (7) / 15/68 / 20/196 / 24/28 / 52/0 / 2.2(1.2;4.0) / 0.12 / 0.01 / 0.23 / 41.96
Pooled / 0.28 / 0.07 / 0.50 / 100
Heterogeneity / p = 0.025 / I-squared / 0.73
Lamivudine vs. placebo / Dienstag, 1999 (5) / 19/71 / 11/72 / 52/16 / 52/16 / 1.8(0.9;3.4) / 0.12 / -0.02 / 0.25 / 48.45
Schiff, 2003 (8) / 40/119 / 9/56 / 52/16 / 52/16 / 2.1(1.1;4.0) / 0.18 / 0.05 / 0.30 / 51.55
Pooled / 0.15 / 0.05 / 0.24 / 100
Heterogeneity / p = 0.519 / I-squared / 0.00
HBeAg seroconversion
Adefovir 10 vs. placebo / Marcellin, 2003 (1) / 20/171 / 9/167 / 48/0 / 48/0 / 2.2(1.0;4.6) / 0.06 / 0.00 / 0.12 / 33.03
Adefovir 30 vs. placebo / Marcellin, 2003 (1) / 23/173 / 9/167 / 48/0 / 48/0 / 2.5(1.2;5.2) / 0.08 / 0.02 / 0.14 / 31.47
Adefovir 10 vs. placebo / Zeng, 2006 (2) / 19/240 / 8/120 / 52/0 / 52/0 / 1.2(0.5;2.6) / 0.01 / -0.04 / 0.07 / 35.5
Pooled / 0.05 / 0.01 / 0.09 / 100
Heterogeneity / p = 0.251 / I-squared / 0.28
Lamivudine vs. placebo / Dienstag, 1999 (5) / 11/71 / 4/72 / 52/0 / 52/0 / 2.8(0.9;8.3) / 0.10 / 0.00 / 0.20 / 13.82
Yao, 1999 (6) / 17/322 / 5/107 / 12/0 / 12/0 / 1.1(0.4;3.0) / 0.01 / -0.04 / 0.05 / 24.06
Perrillo, 2002 (7) / 66/406 / 14/196 / 52/0 / 52/0 / 2.3(1.3;3.9) / 0.09 / 0.04 / 0.14 / 23.18
Schiff, 2003 (8) / 19/119 / 7/56 / 52/0 / 52/0 / 1.3(0.6;2.9) / 0.04 / -0.07 / 0.14 / 12.47
Kim, 2006 (11) / 3/37 / 6/37 / 80/0 / 80/0 / 0.5(0.1;1.9) / -0.08 / -0.23 / 0.07 / 8.31
Lai, 1998 (12) / 22/143 / 3/73 / 48/0 / 48/0 / 3.7(1.2;12.1) / 0.11 / 0.04 / 0.19 / 18.15
Pooled / 0.05 / 0.00 / 0.10 / 100
Heterogeneity / p = 0.028 / I-squared / 0.60
Interferon alfa 2b vs.
placebo / Perrillo, 2002 (7) / 12/68 / 14/196 / 24/28 / 52/0 / 2.5(1.2;5.1) / 0.11 / 0.01 / 0.20 / 89.83
Waked, 1990 (10) / 10/20 / 5/20 / 16/48 / 16/64 / 2.0(0.8;4.8) / 0.25 / -0.04 / 0.54 / 10.17
Pooled / 0.12 / 0.03 / 0.21 / 100
Heterogeneity / p = 0.353 / 0.00
H BsAg loss
Interferon alfa 2b+corticosteroid vs.
no treatment / Perrillo, 1990 (13) / 5/44 / 0/43 / 24/0 / 24/0 / 10.8(0.6;188.8) / 0.11 / 0.01 / 0.21 / 84.73
Robson, 1992 (14) / 1/10 / 0/10 / 24/0 / 24/0 / 3.0(0.1;65.9) / 0.10 / -0.14 / 0.34 / 15.27
Pooled / 0.11 / 0.02 / 0.20 / 100
Heterogeneity / p = 0.917 / 0.00
Improved fibrosis scores
Adefovir 10 vs. placebo / Hadziyannis, 2003 (15) / 59/123 / 15/61 / 48/0 / 48/0 / 2.0(1.2;3.1) / 0.23 / 0.09 / 0.37 / 19.03
Marcellin, 2003 (1) / 62/171 / 35/167 / 48/0 / 48/0 / 1.7(1.2;2.5) / 0.15 / 0.06 / 0.25 / 41.16
Adefovir 30 vs. placebo / Marcellin, 2003 (1) / 78/173 / 35/167 / 48/0 / 48/0 / 2.2(1.5;3.0) / 0.24 / 0.15 / 0.34 / 39.81
Pooled / 0.20 / 0.14 / 0.26 / 100
Heterogeneity / p = 0.395 / 0.00
Improved necroinflammatory scores
Adefovir 10 vs. placebo / Hadziyannis, 2003 (15) / 77/123 / 19/61 / 48/0 / 48/0 / 2.0(1.4;3.0) / 0.32 / 0.17 / 0.46 / 20.07
Hadziyannis, 2005 (16) / 17/80 / 4/40 / 96/0 / 96/0 / 2.1(0.8;5.9) / 0.11 / -0.02 / 0.24 / 22.62
Marcellin, 2003 (1) / 89/171 / 41/167 / 48/0 / 48/0 / 2.1(1.6;2.9) / 0.28 / 0.18 / 0.37 / 28.59
Adefovir 30 vs. placebo / Marcellin, 2003 (1) / 96/173 / 41/167 / 48/0 / 48/0 / 2.3(1.7;3.0) / 0.31 / 0.21 / 0.41 / 28.72
Pooled / 0.26 / 0.17 / 0.34 / 100
Heterogeneity / p = 0.086 / 0.55
Lamivudine vs. placebo / Hadziyannis, 2005 (16) / 37/67 / 3/18 / 48/0 / 48/0 / 3.3(1.2;9.5) / 0.39 / 0.18 / 0.60 / 18.26
Lai, 1998 (12) / 80/143 / 18/73 / 48/0 / 48/0 / 2.3(1.5;3.5) / 0.31 / 0.19 / 0.44 / 27.09
Dienstag, 1999 (5) / 42/71 / 24/72 / 52/0 / 52/0 / 1.8(1.2;2.6) / 0.26 / 0.10 / 0.42 / 23.54
Chan, 2007 (17) / 14/89 / 2/47 / 96/0 / 96/0 / 3.7(0.9;15.6) / 0.12 / 0.02 / 0.21 / 31.12
Pooled / 0.25 / 0.13 / 0.38 / 100
Heterogeneity / p = 0.025 / 0.68
Entecavir vs. lamivudine / Lai, 2006 (18) / 208/325 / 174/313 / 52/0 / 52/0 / 1.2(1.0;1.3) / 0.08 / 0.01 / 0.16 / 35.06
Chang, 2006 (19) / 226/354 / 195/355 / 52/0 / 52/0 / 1.2(1.0;1.3) / 0.09 / 0.02 / 0.16 / 35.79
Sherman, 2006 (20) / 68/141 / 32/145 / 63/0 / 52/0 / 2.2(1.5;3.1) / 0.26 / 0.16 / 0.37 / 29.15
Pooled / 0.14 / 0.04 / 0.24 / 100
Heterogeneity / p = 0.015 / 0.76
HBV DNA undetectable
Adefovir +lamivudine
vs. lamivudine / Perrillo, 2004 (3) / 9/46 / 0/49 / 52/0 / 52/0 / 20.2(1.2;337.7) / 0.20 / 0.08 / 0.31 / 67.89
Peters, 2004 (4) / 7/20 / 0/19 / 48/0 / 48/0 / 14.3(0.9;234.1) / 0.35 / 0.13 / 0.57 / 32.11
Pooled / 0.25 / 0.10 / 0.39 / 100
Heterogeneity / p = 0.219 / 0.34
Adefovir vs. placebo / Hadziyannis, 2003 (15) / 63/123 / 0/61 / 48/0 / 48/0 / 63.5(4.0;1009.3) / 0.51 / 0.42 / 0.60 / 24.93
Hadziyannis, 2005 (16) / 50/80 / 3/40 / 96/0 / 96/0 / 8.3(2.8;25.1) / 0.55 / 0.42 / 0.68 / 22.5
Marcellin, 2003 (1) / 36/171 / 0/167 / 48/0 / 48/0 / 71.3(4.4;1152.3) / 0.21 / 0.15 / 0.27 / 26.24
Zeng, 2006 (2) / 67/240 / 1/120 / 52/0 / 52/0 / 33.5(4.7;238.4) / 0.27 / 0.21 / 0.33 / 26.33
Pooled / 0.38 / 0.23 / 0.53 / 100
Heterogeneity / p = 0.000 / 0.93
Entecavir 0.5 vs. lamivudine / Lai, 2006 (18) / 293/325 / 225/313 / 52/0 / 52/0 / 1.3(1.2;1.4) / 0.18 / 0.12 / 0.24 / 23.17
Chang, 2006 (19) / 236/354 / 129/355 / 52/0 / 52/0 / 1.8(1.6;2.1) / 0.30 / 0.23 / 0.37 / 22.66
Lai, 2002 (21) / 11/43 / 7/40 / 24/0 / 24/0 / 1.5(0.6;3.4) / 0.08 / -0.10 / 0.26 / 16.06
Gish, 2007 (22) / 284/354 / 137/355 / 96/0 / 96/0 / 2.1(1.8;2.4) / 0.42 / 0.35 / 0.48 / 22.89
Entecavir 0.1 vs. lamivudine / Lai, 2002 (21) / 9/34 / 7/40 / 24/0 / 24/0 / 1.5(0.6;3.6) / 0.09 / -0.10 / 0.28 / 15.21
Pooled / 0.23 / 0.11 / 0.35 / 100
Heterogeneity / p = 0.000 / 0.89
Lamivudine vs. placebo / Schiff, 2003 (8) / 34/119 / 8/56 / 52/0 / 52/0 / 2.0(1.0;4.0) / 0.14 / 0.02 / 0.27 / 14.31
Lai, 1998 (12) / 128.7/143 / 16.79/73 / 48/0 / 48/0 / 3.9(2.5;5.9) / 0.67 / 0.56 / 0.78 / 14.51
Liaw, 2000 (23) / 47/93 / 2/41 / 104/0 / 52/52 / 10.4(2.6;40.6) / 0.46 / 0.34 / 0.58 / 14.33
Dienstag, 1999 (5) / 62/71 / 23/72 / 52/0 / 52/0 / 2.7(1.9;3.9) / 0.55 / 0.42 / 0.69 / 14.14
Yao, 2000 (24) / 269/322 / 14/107 / 12/0 / 12/0 / 6.4(3.9;10.4) / 0.71 / 0.63 / 0.78 / 14.92
Chan, 2007 (17) / 23/89 / 3/47 / 96/0 / 96/0 / 4.0(1.3;12.8) / 0.20 / 0.08 / 0.31 / 14.42
Ke, 2006 (25) / 38/42 / 7/30 / 48/0 / 48/0 / 3.9(2.0;7.5) / 0.67 / 0.50 / 0.85 / 13.36
Pooled / 0.48 / 0.31 / 0.66 / 100
Heterogeneity / p = 0.000 / 0.94
Normalization ALT
Adefovir+lamivudine
vs. lamivudine / Perrillo, 2004 (3) / 14/46 / 3/49 / 52/0 / 52/0 / 5.0(1.5;16.2) / 0.24 / 0.09 / 0.39 / 61.21
Peters, 2004 (4) / 10/20 / 1/19 / 48/0 / 48/0 / 9.5(1.3;67.3) / 0.45 / 0.21 / 0.69 / 38.79
Pooled / 0.32 / 0.13 / 0.52 / 100
Heterogeneity / p = 0.158 / 0.50
Adefovir 10 vs. placebo / Hadziyannis, 2003 (15) / 84/123 / 17/61 / 48/0 / 48/0 / 2.5(1.6;3.7) / 0.40 / 0.27 / 0.54 / 17.69
Hadziyannis 2005 (16) / 47/80 / 12/40 / 96/0 / 96/0 / 2.0(1.2;3.3) / 0.29 / 0.11 / 0.47 / 14.16
Marcellin, 2003 (1) / 81/171 / 26/167 / 48/0 / 48/0 / 3.0(2.1;4.5) / 0.32 / 0.23 / 0.41 / 22.6
Zeng, 2006 (2) / 176/240 / 23/120 / 52/0 / 52/0 / 3.8(2.6;5.6) / 0.54 / 0.45 / 0.63 / 22.91
Adefovir 30 vs. placebo / Marcellin, 2003 (1) / 93/173 / 26/167 / 48/0 / 48/0 / 3.5(2.4;5.0) / 0.38 / 0.29 / 0.47 / 22.64
Pooled / 0.40 / 0.30 / 0.49 / 100
Heterogeneity / p = 0.007 / 0.72
Entecavir 1 vs. lamivudine / Chang, 2005 (26) / 19/42 / 2/45 / 48/0 / 48/0 / 10.2(2.5;41.1) / 0.41 / 0.25 / 0.57 / 10.32
Sherman, 2006 (20) / 86/141 / 22/145 / 63/0 / 52/0 / 4.0(2.7;6.0) / 0.46 / 0.36 / 0.56 / 12.22
Entecavir 0.5 vs. lamivudine / Lai, 2002 (21) / 20/43 / 13/40 / 24/0 / 24/0 / 1.4(0.8;2.5) / 0.14 / -0.07 / 0.35 / 8.89
Chang, 2005 (26) / 17/47 / 2/45 / 48/0 / 48/0 / 8.1(2.0;33.2) / 0.32 / 0.17 / 0.47 / 10.71
Lai, 2006 (18) / 253/325 / 222/313 / 52/0 / 52/0 / 1.1(1.0;1.2) / 0.07 / 0.00 / 0.14 / 13
Chang, 2006 (19) / 242/354 / 213/355 / 52/0 / 52/0 / 1.1(1.0;1.3) / 0.08 / 0.01 / 0.15 / 12.94
Gish, 2007 (22) / 193/243 / 112/165 / 96/0 / 96/0 / 1.2(1.0;1.3) / 0.12 / 0.03 / 0.20 / 12.54
Entecavir 0.1 vs. lamivudine / Chang, 2005 (26) / 14/47 / 2/45 / 48/0 / 48/0 / 6.7(1.6;27.8) / 0.25 / 0.11 / 0.40 / 10.9
Pooled / 0.22 / 0.11 / 0.32 / 100
Heterogeneity / p = 0.000 / 0.87
Lamivudine vs. placebo / Kim, 2006 (11) / 2/37 / 2/37 / 80/0 / 80/0 / 1.0(0.1;6.7) / 0.00 / -0.10 / 0.10 / 14.95
Schiff, 2003 (8) / 51/119 / 8/56 / 52/0 / 52/0 / 3.0(1.5;5.9) / 0.29 / 0.16 / 0.41 / 13.56
Lai, 1998 (12) / 68/143 / 12/73 / 48/0 / 48/0 / 2.9(1.7;5.0) / 0.31 / 0.19 / 0.43 / 14.11
Dienstag, 1999 (5) / 27/71 / 5/72 / 52/0 / 52/0 / 5.5(2.2;13.4) / 0.31 / 0.18 / 0.44 / 13.58
Yao, 2000 (24) / 91/322 / 14/107 / 12/0 / 12/0 / 2.2(1.3;3.6) / 0.15 / 0.07 / 0.23 / 16.14
Chan 2007 (17) / 66/89 / 17/47 / 96/0 / 96/0 / 2.1(1.4;3.1) / 0.38 / 0.22 / 0.55 / 11.53
Yao, 1999 (6) / 91/322 / 14/107 / 12/0 / 12/0 / 2.2(1.3;3.6) / 0.15 / 0.07 / 0.23 / 16.14
Pooled / 0.22 / 0.13 / 0.31 / 100
Heterogeneity / p = 0.000 / 0.80
Peginterferon alfa-2a+lamivudine
vs. lamivudine / Marcellin 2004 (27) / 87/181 / 132/181 / 48/0 / 48/0 / 0.7(0.6;0.8) / -0.25 / -0.35 / -0.15 / 46.28
Lau 2005 (28) / 126/271 / 168/272 / 48/0 / 48/0 / 0.8(0.6;0.9) / -0.15 / -0.24 / -0.07 / 53.72
Pooled / -0.20 / -0.29 / -0.10 / 100
Heterogeneity / p = 0.141 / 0.54
Peginterferon alfa-2a+ placebo vs. lamivudine / Marcellin 2004 (27) / 67/181 / 132/181 / 48/0 / 48/0 / 0.5(0.4;0.6) / -0.36 / -0.46 / -0.26 / 48.09
Lau, 2005 (28) / 105/271 / 168/272 / 48/0 / 48/0 / 0.6(0.5;0.7) / -0.23 / -0.31 / -0.15 / 51.91
Pooled / -0.29 / -0.42 / -0.17 / 100
Heterogeneity / p = 0.045 / 0.75
Adefovir vs. placebo / Hadziyannis, 200 (16) / 43/80 / 12/40 / 96/18 / 96/0 / 1.8(1.1;3.0) / 0.24 / 0.06 / 0.42 / 15.83
Zeng, 2006 (2) / 140/360 / 15/120 / 12/40 / 12/40 / 3.1(1.9;5.1) / 0.26 / 0.19 / 0.34 / 84.17
Pooled / 0.26 / 0.19 / 0.33 / 100
Heterogeneity / p = 0.791 / 0.00
Interferon Alfa 2b vs.
no treatment / Di Bisceglie, 1993 (9) / 9/25 / 0/22 / 16/8 / 16/8 / 16.8(1.0;273.1) / 0.36 / 0.17 / 0.55 / 49.19
Perrillo, 1990 (13) / 18/41 / 8/43 / 24/24 / 24/24 / 2.4(1.2;4.8) / 0.25 / 0.06 / 0.44 / 50.81
Pooled / 0.31 / 0.17 / 0.44 / 100
Heterogeneity / p = 0.442 / 0.00
Peginterferon alfa-2a+lamivudine vs. lamivudine / Marcellin, 2004 (27) / 107/181 / 80/181 / 48/24 / 48/24 / 1.3(1.1;1.6) / 0.15 / 0.05 / 0.25 / 37.5
Lau, 2005 (28) / 106/271 / 76/272 / 48/24 / 48/24 / 1.4(1.1;1.8) / 0.11 / 0.03 / 0.19 / 62.5
Pooled / 0.13 / 0.06 / 0.19 / 100
Heterogeneity / p = 0.569 / 0.00
Peginterferon alfa-2a+placebo vs. lamivudine / Marcellin, 2004 (27) / 105/181 / 80/181 / 48/24 / 48/24 / 1.3(1.1;1.6) / 0.14 / 0.04 / 0.24 / 37.61
Lau, 2005 (28) / 111/271 / 76/272 / 48/24 / 48/24 / 1.5(1.2;1.9) / 0.13 / 0.05 / 0.21 / 62.39
Pooled / 0.13 / 0.07 / 0.20 / 100
Heterogeneity / p = 0.904 / 0.00
Interferon alfa-2b+lamivudine vs. lamivudine / Barbaro. 2001 (29) / 9/76 / 11/75 / 24/0 / 52/0 / 0.8(0.4;1.8) / -0.03 / -0.14 / 0.08 / 18.21
Schiff, 2003 (8) / 0/63 / 52/119 / 52/0 / 52/0 / 0.0(0.0;0.3) / -0.44 / -0.53 / -0.35 / 18.59
Sarin, 2005 (30) / 6/38 / 3/37 / 52/0 / 52/0 / 2.0(0.5;7.2) / 0.08 / -0.07 / 0.22 / 17.2
Shi, 2006 (31) / 0/64 / 22/98 / 48/0 / 48/0 / 0.0(0.0;0.6) / -0.22 / -0.31 / -0.14 / 18.72
Akyuz, 2007 (32) / 10/21 / 13/24 / 96/0 / 96/0 / 0.9(0.5;1.6) / -0.07 / -0.36 / 0.23 / 12.49
Economou, 2005 (33) / 2/24 / 12/26 / 96/0 / 96/0 / 0.2(0.0;0.7) / -0.38 / -0.60 / -0.16 / 14.79
Pooled / -0.18 / -0.35 / -0.01 / 100
Heterogeneity / p = 0.000 / 0.91
Lamivudine vs. placebo / Schiff, 2003 (8) / 52/119 / 0/56 / 52/0 / 52/0 / 49.9(3.1;793.6) / 0.44 / 0.35 / 0.53 / 26.59
Liaw, 2004 (34) / 209/436 / 11/215 / 130/0 / 130/0 / 9.4(5.2;16.8) / 0.43 / 0.37 / 0.48 / 73.41
Pooled / 0.43 / 0.38 / 0.48 / 100
Heterogeneity / p = 0.873 / 0.00
References: