Table 1.
Absolute Risk Difference in Tested Intermediate Outcomes After Antiviral Drugs for Chronic Hepatitis B in Adults
| Comparison | HBsAg [RCTs/patients] | HBeAg [RCTs/patients] | HBV DNA clearance [RCTs/patients] | Histology improved [RCTs/patients] | ALT normal [RCTs/patients] | Relapse/Mutation [RCTs/patients] |
|---|---|---|---|---|---|---|
| Adefovir vs. placebo | SC: NS [1/120] L | Loss: 0.11 (0.06; 0.16) [2/995] M | 0.38 (0.23; 0.53) [4/1002] H | Fibrosis: 0.20 (0.14; 0.26) [2/699] M | 0.40 (0.30; 0.49) [5/1342] | NS [2/1055] L |
| SC: 0.05 (0.01; 0.09) | 20.41 (6.79; 61.32) [4/1002] | Necroinflammation scores: | 2.97 (2.38; 3.69) H | NS* [1/140] L | ||
| [2/700] H | 0.59 (0.46; 0.72)* [1/120] L | 0.26 (0.17; 0.34) [3/819] H | 0.26 (0.19; 0.33)* [2/600] M | |||
| LAM vs. placebo | Loss: NS [1/175] L | Loss: 0.13 (0.04; 0.22) [4/1349] M | 0.48 (0.31; 0.66) [7/1305]H | Necroinflammation: | 0.22 (0.13; 0.31) [7/1602]M | YMDD mutation: 0.43 (0.38; 0.48) [2/826] H |
| NS* [3/1068] L | 0.15 (0.05; 0.24)* [2/318] M | 3.79 (2.71; 5.30) H | 2.09 (1.60; 2.74) M | 2.42 (1.94; 3.01) M | ||
| SC: 0.05 (0.001; 0.10) [6/1638] H | 0.08 (0.00; 0.15)* [1/136] L | 0.25 (0.13; 0.38) [4/580] M | 0.21 (0.04; 0.38)* [1/136] L | |||
| 1.70 (1.05; 2.74) | ||||||
| NS * [2/318] L | ||||||
| Adefovir + LAM vs. LAM | Loss: NS [1/39] L | Loss: 0.12 (0.03; 0.21) [2/134] M | 0.25 (0.10; 0.39) | 0.32 (0.13; 0.52) [2/13] M | YMDD:-0.33 (-0.50; -0.17) [1/95] L | |
| SC: NS [2/134] L | [2/134] L | Wild type mutation: NS [1/95] L | ||||
| Adefovir + LAM vs. adefovir | Loss: NS [1/39] L | Loss: NS [1/39] L | NS:[1/39] L | NS [1/39] L | ||
| SC: NS[1/39] L | ||||||
| Entecavir vs. LAM | Loss: NS [2/1117] M | Loss: NS [3/1112] L | 0.23 (0.11; 0.35) [4/1636] | Necroinflammation: 0.14 (0.04; 0.24) [3/1633] M | 0.22 (0.11; 0.32) [6/2423] | NS [0/1347] L |
| SC: NS [1/408] L | SC: NS [3/1185] M | 1.64 (1.22; 2.22) | Fibrosis: NS [2/995] M | 1.62 (1.28; 2.06) H | -0.16 (-0.20; -0.12)* [1/709] L | |
| L/M NS*1/709] L | ||||||
| LAM vs. adefovir | Loss: NS [1/38] L | -0.26 (-0.47; -0.06) [1/38] L | -0.42 (-0.67; -0.18) [1/38] L | |||
| SC:NS [1/38] L | ||||||
| LAM vs. telbivudine | Loss: NS [1/63] L | -0.30 (-0.55; -0.04) [1/63] L | NS [1/85] L | NS [1/63] L | ||
| SC: NS [1/63] L | ||||||
| Telbivudine vs. adefovir | Loss: NS [1/135] L | 0.28 (0.12; 0.44) | NS [1/135] L | |||
| SC: 6.03 (2.20; 16.52) [1/136] L | [1/136] L | |||||
| Telbivudine + LAM vs. LAM | Loss: NS[1/60] L | NS [1/60] L | NS [1/101] L | NS [1/60] L | ||
| SC: NS [1/60] L | ||||||
| Telbivudine + LAM vs. telbivudine | Loss: NS [1/85] L | NS [1/85] L | NS [1/101] L | NS [1/85] L | ||
| SC: NS [1/85] L | ||||||
| Interferon alfa-2b vs. placebo | Loss: NS [3/166] M | Loss: 0.55 (0.29; 0.81) | 0.45 (0.22; 0.68) | Total scores: NS* [1/40] L | 0.31 (0.17; 0.44)* [2/131] M | Relapse: NS* [5/378] H |
| NS* [4/247] L | [1/40] L | [1/34] L | HAI scores:0.24 (0.00; 0.48) [1/72] L | |||
| SC: NS* [2/82] L | 2.52 (1.55; 4.10) | 0.44 (0.27; 0.60)* [3/168] L | ||||
| 0.28 (0.07; 0.50)* [3/351] M | ||||||
| SC:NS [1/40] L | ||||||
| 0.12 (0.03; 0.21) * [2/304] M | ||||||
| Interferon alfa-2b + lamivudine vs. placebo | Loss: 0.06 (0.00; 0.13) [1/119] L | Loss: NS [1/118] L | 0.48 (0.33; 0.63) [1/119] L | HAI scores | NS [1/119] L | YMDD mutation |
| NS* [1/119] L | NS* [2/450] M | NS* [1/119] L | NS [1/119] L | NS [1/118] L | ||
| SC: NS [1/119] L | ||||||
| NS* [2/450] L | ||||||
| Interferon alfa-2b + corticosteroid vs. no treatment | Loss: 0.11 (0.02; 0.20) [2/103] M | 0.25 (0.04; 0.46) [1/34] L | 0.25 (0.06; 0.43)* [1/87] L | Relapse | ||
| NS* [2/121] M | NS* [1/87] L | |||||
| Interferon alfa-2b vs. LAM | Loss: NS [1/151] L | NS [1/76] L | Knodell scores: NS* [1/151] L | NS [1/151] L | YMDD mutation | |
| NS* [2/625] M | NS* [1/151] L | NS* [2/151] L | -0.23 (-0.33; -0.14)* [1/151] L | |||
| SC: NS[1/151] L | ||||||
| NS* [3/776] M | ||||||
| Interferon Alfa 2b + LAM vs. interferon alfa-2b | Loss: NS [1/144] L | NS [1/144] L | HAI scores | NS [1/144] L | YMDD mutation | |
| NS* [2/347] M | NS* [2/278] L | 0.54 (0.28; 0.79) [1/48] L | NS* [2/192] L | NS* [1/144] L | ||
| SC: NS [1/144] L | Knodell scores | |||||
| NS* [3/482] L | NS* [1/144] L | |||||
| Interferon alfa-2b + LAM vs. LAM | Loss: | Loss: NS [3/414] M | NS [7/786] H | HAI scores | NS [5/626] M | Relapse: NS [4/326] H |
| NS [2/262] L | NS* [5/1167] M | NS* [4/365] M | NS [3/327] M | NS* [6/751] M | NS* [2/158] L | |
| NS* [3/495] L | SC: NS [4/565] H | necroinflammation NS [2/389] L | YMDD mutation: | |||
| NS* [3/490] M | Knodell scores | -0.18 (-0.35; -0.01) [6/721] M | ||||
| NS* [1/157] L | 0.42 (0.16; 1.09) M | |||||
| -0.23 (-0.32; -0.14)* [1/157] L | ||||||
| Interferon alfa-2b + corticosteroid vs. IFN alfa-2b | Loss: NS [2/125] M | Loss: NS [2/77] L | NS [2/77] L | NS* [3/170] M | Relapse: NS* [2/141] L | |
| NS* [3/141] L | NS* [3/122] L | NS* [6/322] H | ||||
| SC: NS* [2/85] L | ||||||
| Peginterferon alfa-2a vs. LAM | Loss: 0.08 (0.01; 0.16) M | -0.15 (-0.22; -0.07) [1/543] M | Necroinflammation | -0.29 (-0.42; -0.17) [2/905] | YMDD mutation | |
| 0.13 (0.05; 0.20)* [1/543] M | 0.12 (0.02; 0.22) [1/552]* L | 0.57 (0.46; 0.70) [2/905] M | -0.25 (-0.31; -0.20) [1/543] L | |||
| SC: NS [1/543] L | 0.09 (0.04; 0.14) [1/543]* L | Fibrosis: NS* [1/552] L | 0.13 (0.07; 0.20)* [2/905] H | |||
| 0.13 (0.06; 0.20) [1/814]* M | HAI: NS [2/1366]* M | |||||
| Peginterferon alfa-2a + LAM vs. LAM | Loss: NS [1/543] L | 0.29 (0.21; 0.37) [1/543] M | Total scores: NS [2/1366]* H | -0.20 (-0.29; -0.10) [2/905] H | YMDD mutation | |
| 0.07 (0.00; 0.15)* [1/543] M | 0.09 (0.04; 0.13) [1/543]* L | 0.13 (0.06; 0.19) [2/905]* H | -0.22 (-0.28; -0.16) [1/543] L | |||
| SC: NS [1/543] L | ||||||
| 0.08 (0.01; 0.15) *[1/814] L | ||||||
| Peginterferon alfa-2a + LAM vs. peginterferon alfa-2a | Loss: NS [1/542] L | 0.44 (0.36; 0.51) [1/542] M | Total scores: NS [1/96]* L | NS [1/542] L | YMDD mutation: 0.03 (0.01; 0.06) [1/542] L | |
| NS [1/542]* M | NS[1/542]* L | NS [1/542]* L | ||||
| SC: NS [1/542] L | ||||||
| NS [1/814]* L | ||||||
| Peginterferon alfa-2b vs. interferon alfa-2b | SC: NS* [1/230] | Loss: 0.10 (0.00; 0.21) [1/230]* L | NS [1/230]* L | |||
| Peginterferon alfa-2b + LAM vs. LAM | Negative HBVDNA + HBsAg SC | Loss: 0.34 (0.16; 0.52) [1/100] M | NS [1/100] L | HAI scores | NS [1/100] L | NS: [1/100]* L |
| 0.32 (0.14; 0.50) [1/100] | SC: 0.32 (0.14; 0.50) | NS [1/100]* L | NS: [1/100] L | YMDD mutation: NS [1/100] L | ||
| [1/100] L | ||||||
| NS: [1/100]* L | ||||||
| Peginterferon alfa-2b + LAM vs. peginterferon alfa-2b | Loss: NS [1/307] | Loss: 0.12 (0.01; 0.22) [1/307] M | fibrosis scores: NS [1/307]* L | 0.14 (0.03; 0.24) [1/307] L | YMDD mutation: 0.09 (0.04; 0.14) [1/307] L | |
| NS [2/614]* M | necroinflammation scores: NS [1/307] L | NS [1/307]* L | ||||
| SC: NS [1/307]L | ||||||
| NS: [1/307]* L |
SC = seroconversion; NS = not significant; italic = relative risk; * = outcomes off treatments; LAM = lamivudine
Level of evidence: L = low; M = moderate; H = high