Table E10Summary tables of the effects of therapies for CHB in patient subpopulations by baseline status of chronic hepatitis B

OutcomeComparisonWeeks of Treatments/Followup off the TreatmentN Studies/EnrolledAuthorRelative Risk or Odds ratios (95% CI)Comments
Baseline histology, outcomes at the end of the treatment
Overall disease progression - an increase of at least 2 points in the Child-Pugh score (5 indicates good and 15 -poor liver function) Lamivudine vs. placebo 130/0 1/651 Liaw, 2004510.44 (0.23; 0.84)disease progression was lowered among patients with baseline Child-Pugh score=5
0.37 (0.16; 0.86)disease progression was lowered among patients with baseline Child-Pugh score=6
0.37 (0.19; 0.71)disease progression was lowered among patients with baseline Ishak fibrosis score=6
Random differences among patients with baseline Child-Pugh score >7 and Ishak fibrosis score <4 or 5
Adjusted for treatment OR of HBeAg LossLamivudine vs. placebo52/01/602Perrillo, 20021041.17 (1.10; 1.24)HBeAg loss was higher per 1 unit increase in baseline HAI score
HBeAg loss irrespective of HBV-DNA status at baseline or week 56 Lamivudine vs. placebo 52/0 1/602 Perrillo, 20021041.45 (0.40; 5.29) HBeAg loss did not differ after lamivudine vs. placebo among the patients with pretreatment HAI Score 0–4
4.02 (1.23; 13.16)HBeAg loss was higher among the patients with baseline HAI Score 5–9
2.27 (1.28; 4.02)HBeAg loss was higher among the patients with baseline HAI Score >10
Worsening of Knodell necroinflammatory scoreLamivudine vs. placebo48/01/216Lai, 1998500.11 (0.03; 0.51)Worsening of Knodell necroinflammatory score after lamivudine vs. placebo was less frequent among patients with moderate or severe hepatitis
Histological response - reduction of 2 or more points in the Knodell necroinflammatory score between baseline and week 52 Lamivudine vs. placebo 48/0 1/216 Lai, 1998502.30 (1.39; 3.81)Lamivudine improved histology compared to placebo among the patients with moderate or severe hepatitis
2.17 (0.76; 6.21)Lamivudine did not improve histology compared to placebo among the patients with mild hepatitis
Baseline viral load, outcomes at the end of the treatment
HBeAg loss, loss of detectable HBV DNA, and seroconversion to antiHBeAg Interferon Alfa 2b+lamivudine vs. lamivudine 52/0 1/75 Sarin, 2005692.92 (0.63; 13.56) Random differences among the patients with baseline HBV DNA >107 copies/mL
HBeAg loss 1.62 (0.66; 4.01) Random differences among patients with baseline HBV DNA >107 copies/mL
HBeAg loss with antiHBeAg appearance2.92 (0.63; 13.56)Random differences among patients with baseline HBV DNA >107 copies/mL
HBeAg loss Interferon Alfa 2b vs. no treatment 32/0 1/118 Janssen, 1999834.20 (0.95; 18.64) Random differences among the patients with baseline HBV DNA <10pg/ml
0.19 (0.01; 3.82)Random differences among patients with baseline HBV DNA >10pg/ml
OR of hepatic decompensation: change in the Child-Turcotte-Pugh score of 2 or more points adjusted for treatments, ALT, HBV DNA, sex, YMDD variant, platelet, bilirubin, albuminLamivudine vs. no treatment80/01/74Kim, 200654Random association with baseline HBV DNA
OR of flare - elevation of ALT activity to >10 times the ULN and to > twice the baseline value with detectable HBV DNA- adjusted for treatments, ALT, HBV DNA, sex, YMDD variant, platelet, bilirubin, albuminLamivudine vs. no treatment80/01/74Kim, 200654Random association with baseline HBV DNA
Overall disease progression - an increase of at least 2 points in the Child-Pugh score Lamivudine vs. placebo 130/0 1/651 Liaw, 2004510.22 (0.07; 0.70)Disease progression was lower among the patients with baseline HBV DNA below the lower limit of quantitation
0.77 (0.34; 1.74) Disease progression was not lower among the patients with baseline HBV DNA 0.7–10 meq/ml
0.37 (0.13; 1.05) Disease progression was lower among the patients with baseline HBV DNA >10–100 meq/ml
0.41 (0.18; 0.94)Disease progression was lower among the patients with baseline HBV DNA >100 meq/ml
Adjusted for treatments odds ratio of HBeAg lossLamivudine vs. placebo52/01/602Perrillo, 20021040.99 (0.97; 1.00)HBeAg loss was not associated with baseline HBV-DNA level (per 10-unit increase)
HBV DNA lossLamivudine vs. placebo12/01/429Yao, 19991126.41 (3.92; 10.47)HBV DNA loss among patients with baseline HBV DNA >1.6pg/ml
Adjusted OR of sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/mlPeginterferon alfa-2a vs. lamivudine48/01/1036Bonino, 20071141.28 (1.10; 1.40)Sustained combined response was increased by 1 log 10 unit (copies/ml) decrease in baseline HBV DNA
Baseline HBeAg status, outcomes at the end of the treatment
Overall disease progression - an increase of at least 2 points in the Child-Pugh score Lamivudine vs. placebo 130/0 1/651 Liaw, 2004510.72 (0.36; 1.43) lamivudine did not decrease compared to placebo disease progression among HBeAg- at baseline patients
0.30 (0.16; 0.55)lamivudine decreased compared to placebo disease progression among HBeAg+ at baseline patients
Undetectable HBV DNA level by bDNA assay and normal ALT levelEntecavir (dose)48/01/182Change, 200576No dose response association among patients with baseline HBeAg + or HBeAg - status
Undetectable HBV DNA level by bDNA assay and normal ALT level Entecavir vs. lamivudine 48/0 1/182 Change, 20057618.38
(1.18; 285.96)
entecavir in dose 1 mg/day vs. lamivudine resulted in higher rates of undetectable HBV DNA level by bDNA assay and normal ALT level among the patients with HBeAg- baseline status
Entecavir in doses 0.5 or 0.1mg/day did not result in significant differences compared to lamivudine
1.19 (0.18; 7.86)entecavir in dose 1, 0.5, or 0.1 mg/day vs. lamivudine did not result in higher rates of undetectable HBV DNA level by bDNA assay and normal ALT level among the patients with HBeAg+ baseline status
HBV DNA >4 log 10 copies/ml Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.55 (0.27; 1.13) No differences between telbivudine vs. lamivudine among patients with HBeAg- status at baseline
0.67 (0.54; 0.82)telbivudine vs. lamivudine reduced the rates of detectable HBV DNA among the patients with HBeAg+ baseline status
ALT normalization Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.94 (0.84; 1.04) No differences between telbivudine vs. lamivudine among patients with HBeAg- status at baseline
1.03 (0.96; 1.11)No differences between telbivudine vs. lamivudine among patients with HBeAg+ status at baseline
HBV DNA <3 log 10 copies/ml Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.91 (0.49; 1.67) No differences between telbivudine vs. lamivudine among patients with HBeAg- status at baseline
0.93 (0.67; 1.29)No differences between telbivudine vs. lamivudine among patients with HBeAg+ status at baseline
Ishak fibrosis scores improved Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007711.28 (1.07; 1.54)telbivudine vs. lamivudine improved fibrosis scores among patients with HBeAg - status at baseline
1.11 (1.01; 1.23)RR, telbivudine vs. lamivudine improved fibrosis scores among patients with HBeAg+ status at baseline
Primary treatment failure -serum HBV DNA levels remained above 5 log 10 copies per milliliter Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.17 (0.02; 1.39) No differences between telbivudine vs. lamivudine among patients with HBeAg-status at baseline
0.36 (0.22; 0.57)telbivudine vs. lamivudine reduced the rates of treatment failure among patients with HBeAg + at baseline
Reduction of at least 2 points in the Knodell necroinflammatory score, with no worsening in the fibrosis score Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007711.01 (0.88; 1.15) no differences between telbivudine vs. lamivudine among patients with HBeAg- status at baseline
1.15 (1.03; 1.27)telbivudine vs. lamivudine improved necroinflammatory score, with no worsening in the Knodell fibrosis score among patients with HBeAg +status at baseline
Serum HBV DNA undetectable by PCR Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007711.24 (1.12; 1.36)telbivudine vs. lamivudine increased HBV DNA loss among patients with HBeAg -status at baseline
1.49 (1.30; 1.70)telbivudine vs. lamivudine increased HBV DNA loss among patients with HBeAg + status at baseline
Viral breakthrough - at least 2 consecutive determinations of an increase in HBV DNA by at least 1 log10 copy per milliliter from nadir Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.18 (0.07; 0.46)telbivudine vs. lamivudine reduced the rates of viral breakthrough among patients with HBeAg -status at baseline
0.38 (0.25; 0.59)telbivudine vs. lamivudine reduced the rates of viral breakthrough among patients with HBeAg + status at baseline
Viral breakthrough - at least 2 consecutive determinations of an increase in HBV DNA by at least 1 log10 copy per milliliter from nadir with treatment-emergent resistance mutations Telbivudine vs. lamivudine 52/0 1/1367 Lai, 2007710.21 (0.08; 0.54)telbivudine vs. lamivudine reduced the rates of viral breakthrough among patients with HBeAg -status at baseline
0.46 (0.28; 0.73)telbivudine vs. lamivudine reduced the rates of viral breakthrough among patients with HBeAg + status at baseline
Genotype, outcomes at the end of the treatment
Adjusted OR of sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a vs. lamivudine 48/0 1/1036 Bonino, 20071140.42 (0.10; 1.20) No differences in sustained response between genotype A vs. B
0.33 (0.10; 0.90)Patients with genotype A vs. C had lower adjusted rates of sustained response
0.97 (0.30; 2.70) No differences in sustained response between genotype A vs. D
0.79 (0.50; 1.30) No differences in sustained response between genotype B vs. C
2.31 (1.30; 4.20)Patients with genotype B vs. D had higher adjusted rates of sustained response
2.90 (1.70; 5.00)Patients with genotype C vs. D had higher adjusted rates of sustained response
YMDD mutation, outcomes at the end of the treatment
OR of flare - elevation of ALT activity to >10 times the ULN and to > twice the baseline value with detectable HBV DNA-adjusted for treatments, ALT, HBV DNA, sex, YMDD variant, platelet, bilirubin, albuminLamivudine vs. no treatment80/01/74Kim, 200654Random association with YMDD mutation
OR of hepatic decompensation change in the Child-Turcotte-Pugh score of 2 or more points adjusted for treatments, ALT, HBV DNA, sex, YMDD variant, platelet, bilirubin, albuminLamivudine vs. no treatment80/01/74Kim, 200654Random association with YMDD mutation
Change in necroinflammation: worsening Lamivudine vs. placebo 48/0 1/85 Yuen, 20051110.15 (0.04; 0.54)Lamivudine vs. placebo reduced the rates of worsened histology among patients without YMDD mutation
0.18 (0.01; 2.87)Lamivudine vs. placebo did not reduce the rates of worsened histology among patients with YMDD mutation
Change in fibrosis: worsening Lamivudine vs. placebo 48/0 1/85 Yuen, 20051110.90 (0.27; 2.98) Lamivudine vs. placebo did not reduce the rates of worsened histology among patients without YMDD mutation
0.86 (0.11; 6.92)Lamivudine vs. placebo did not reduce the rates of worsened histology among patients with YMDD mutation
Change in necroinflammation: Improvement Lamivudine vs. Placebo 48/0 1/85 Yuen, 20051113.30 (1.15; 9.51)Lamivudine vs. placebo improved histology among patients without YMDD mutation
3.43 (1.02; 11.57)Lamivudine vs. placebo improved histology among patients with YMDD mutation
Change in fibrosis: Improvement Lamivudine vs. placebo 48/0 1/85 Yuen, 20051110.30 (0.02; 4.56) Lamivudine vs. placebo did not improve fibrosis scores among patients without YMDD mutation
0.79 (0.04; 17.44)Lamivudine vs. placebo did not improve fibrosis scores among patients with YMDD mutation
Baseline ALT, at followup off the treatment
Active hepatitisInterferon Alfa 2b+corticosteroid vs. interferon Alfa 2b24/241/56Zarski, 1994910.81 (0.22; 2.91)random differences among patients with baseline ALT <3ULN
CirrhosisInterferon Alfa 2b+corticosteroid vs. interferon Alfa 2b24/241/56Zarski, 1994910.40 (0.04; 4.19)random differences among patients with baseline ALT <3ULN
HBV DNA loss Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b 24/24 1/115 Wai, 20021021.22 (1.05; 1.42)HBV DNA loss was more frequent among patients with elevated baseline ALT
1/56Zarski, 1994912.42 (0.27; 21.86)random differences among patients with baseline ALT <3ULN
Loss of HBV DNA + HBeAg seroconversion Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b 24/24 2/95 Zarski, 199491Random changes in both studies among elevated ALT
Lok, 199293
Loss of HBV DNA and HBeAgInterferon Alfa 2b+corticosteroid vs. interferon Alfa 2b24/241/85Perrillo, 199096Random changes in all groups with elevated ALT level
Loss of HBV DNA, HBeAg, and HBsAgInterferon Alfa 2b+corticosteroid vs. interferon Alfa 2b24/241/39Lok, 1992930.29 (0.01; 6.66)random differences among patients with elevated baseline ALT
HBsAg lossInterferon Alfa 2b+corticosteroid vs. interferon Alfa 2b24/241/56Zarski, 1994913.23 (0.38; 27.06)random differences among patients with baseline ALT <3ULN
Loss of HBV DNA + HBeAg seroconversionInterferon Alfa 2b+corticosteroid vs. no treatment24/241/37Lok, 1992932.29 (0.74; 7.10)random differences among patients with elevated baseline ALT
Loss of HBV DNA, HBeAg, and HBsAgInterferon Alfa 2b+corticosteroid vs. no treatment24/241/37Lok, 1992930 events in both treatment groups
Loss of HBV DNA and HBeAgInterferon Alfa 2b+corticosteroid vs. no treatment24/241/43Perrillo, 1990967.82 (1.02; 59.88)Loss of HBV DNA and HBeAg was greater among patients with baseline ALT <100U/L with random differences among those with baseline ALT100–200 and >200U/L
HBeAg lossInterferon Alfa 2b+lamivudine vs. interferon Alfa 2b24/281/203Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
HBeAg seroconversion Interferon Alfa 2b+lamivudine vs. interferon Alfa 2b 24/28 2/347 Schalm, 200067Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
Perrillo, 2002104
Odds ratio of sustained virologic response (sustained suppression of serum levels of HBeAg and HBV DNA) in those with baseline ALT levels of 150 or more independent of gender and ageInterferon Alfa 2b+lamivudine vs. lamivudine24/481/150Barbaro, 2001663.12 (1.43; 6.82)Adjusted odds of virologic response were higher in patients with baseline ALT >150UL
HBeAg lossInterferon Alfa 2b+lamivudine vs. lamivudine24/281/541Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
HBeAg seroconversion Interferon Alfa 2b+lamivudine vs. lamivudine 24/28 2/698 Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
Schalm, 200067
HBeAg lossInterferon Alfa 2b+lamivudine vs. placebo24/281/331Perrillo, 20021042.90 (1.35; 6.27)HBeAg loss was higher among patients with ALT >2 but <5ULN with random differences among those with <1ULN or 1–2ULN
HBeAg seroconversion Interferon Alfa 2b+lamivudine vs. placebo 24/28 1/331 Perrillo, 20021042.70 (1.10; 6.58)HBeAg seroconversion was greater among patients with >2-<5 ULN
3.27 (1.03; 10.39)HBeAg seroconversion was greater among patients with ALT >5 ULN with random differences among those with baseline ALT<1ULN or 1–2ULN
HBeAg seroconversionInterferon Alfa 2b+placebo vs. lamivudine24/281/151Schalm, 200067Random differences among patients with baseline ALT <2, 2–5, or >5ULN
Partial antiviral response: sustained clearance of serum HBV DNA by direct spot hybridization (lower limit of detection of 10 pg/mL) and clearance of HBeAg but not HBsAgInterferon Alfa 2b+placebo vs. no treatment24/241/34Lok, 1992931.48 (0.42; 5.24)Random differences in patients with elevated ALT
Complete antiviral response: sustained clearance of serum HBV DNA by direct spot hybridization (lower limit of detection of 10 pg/mL) and clearance of HBeAg and HBsAg24/241/34Lok, 1992932.68 (0.12; 61.58)Random differences in patients with elevated ALT
HBeAg lossInterferon Alfa 2b vs. lamivudine24/281/474Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
HBeAg seroconversionInterferon Alfa 2b vs. lamivudine24/281/474Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
Loss of HBV DNA and HBeAgInterferon Alfa 2b vs. no treatment24/241/84Perrillo, 199096Random differences among patients with baseline ALT <100, 100–200, and >200U/L
HBeAg lossInterferon Alfa 2b vs. placebo24/280/264Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
HBeAg seroconversion24/280/264Perrillo, 2002104Random differences among patients with baseline ALT <1ULN, 2–5ULN, and >5 ULN
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/mlPeginterferon alfa-2a+lamivudine vs. lamivudine48/241/202Bonino, 2007114Random differences among patients with baseline ALT 2–5 and >5 ULN
Adjusted for treatment status odds ratio of sustained response: HBeAg seroconversion, HBV DNA loss and ALT normalization in HBeAg (+) patients. In HBeAg (-) patients: loss of HBV DNA+ALT normalizationpeginterferon alfa-2a+lamivudine vs. lamivudine9/241/140Cindoruk, 200711510.32 (9.71; 10.97)Sustained response was greater per increase in 1unit (U/L) in baseline ALT
HBeAg seroconversionPeginterferon alfa-2a+lamivudine vs. lamivudine48/241/542Lau, 2005561.93 (1.01; 3.69)Response was greater among patients with baseline ALT >5ULN, random differences among those with baseline ALT <2 or 2–5ULN
HBeAg seroconversionPeginterferon alfa-2a+lamivudine vs. peginterferon alfa-2a48/241/542Lau, 200556Random differences among patients with baseline ALT <2, 2–5, and >5 ULN
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/mlPeginterferon alfa-2a+placebo vs. lamivudine48/241/202Bonino, 2007114Random differences among patients with baseline ALT <2, 2–5, and >5 ULN
HBeAg seroconversionPeginterferon alfa-2a+placebo vs. lamivudine48/241/542Lau, 2005561.81 (1.07; 3.04)HBeAg seroconversion was greater in patients with baseline ALT >2 but <5ULN. Random differences among those with baseline ALT <2 or >5ULN
Adjusted odds ratios of sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/mlPeginterferon alfa-2a vs. lamivudine48/241/1036Bonino, 2007114Random association per 1 U/L increase in baseline ALT
Adjusted for treatment allocation, hepatitis B virus (HBV) genotype and log HBV DNA odds ratio of persistent HBeAg loss at any time up to week 76 of post-treatment followupPeginterferon alfa-2b+lamivudine vs. lamivudine60/241/100Chan, 2006118Random association per 1 U/L increase in baseline ALT
Adjusted for treatment allocation, HBV DNA genotype, IL-1b-511 polymorphism, baseline log HBV DNA odds ratio of persistent HBeAg loss and at any time up to week 76 of post-treatment followupPeginterferon alfa-2b+lamivudine vs. lamivudine60/241/100Chan, 2006118Random association per 1 U/L increase in baseline ALT
Adjusted odds ratio of sustained HBeAg lossPeginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b52/261/310Janssen, 200578Random differences among patients with elevated vs. normal baseline ALT
Multivariate adjusted odds ratio of sustained combined response: HBeAg negative, HBV DNA <5 log10 copies/mL, and normal ALT levelPeginterferon alfa-2b+vs. interferon Alfa 2b24/241/230Zhao, 2007811.23 (0.51; 2.92)RR, random differences between patients with baseline ALT level >3.4 vs. <3.4 ULN
Baseline histology at followup off the treatment
HBeAg loss Interferon Alfa 2b vs. placebo 24/28 1/264 Perrillo, 20021043.84 (0.88; 16.74) Interferon Alfa 2b vs. placebo did not increase HBeAg loss among patients with pretreatment HAI score 0–4
5.76 (1.48; 22.42)Interferon Alfa 2b vs. placebo increased HBeAg loss among patients with pretreatment HAI score 5–9
1.11 (0.41; 2.99)Interferon Alfa 2b vs. placebo did not increase HBeAg loss among patients with pretreatment HAI score >10
HBeAg loss Interferon Alfa 2b+lamivudine vs. placebo 24/28 1/331 Perrillo, 20021043.39 (0.89; 12.87) Interferon Alfa 2b+lamivudine vs. placebo did not increase HBeAg loss in patients with pretreatment HAI Score 0–4
5.32 (1.51; 18.72)Interferon Alfa 2b+lamivudine vs. placebo increased HBeAg loss in patients with pretreatment HAI Score 5–9
1.79 (0.89; 3.59)Interferon Alfa 2b+lamivudine vs. placebo did not increase HBeAg loss in patients with pretreatment HAI Score >10
HBeAg loss Interferon Alfa 2b vs. lamivudine 24/28 1/331 Perrillo, 20021042.65 (0.84; 8.38) Interferon Alfa 2b vs. lamivudine did not increase HBeAg loss in patients with pretreatment HAI Score 0–4
1.43 (0.61; 3.36) Interferon Alfa 2b vs. lamivudine did not increase HBeAg loss in patients with pretreatment HAI Score 5–9
0.49 (0.20; 1.17)Interferon Alfa 2b vs. lamivudine did not increase HBeAg loss in patients with pretreatment HAI score >10
Odds ratio of sustained virologic response (sustained suppression of serum levels of HBeAg and HBV DNA) in those with a baseline inflammation score of 7 or more independent on gender and age Interferon Alfa 2b+ lamivudine vs. lamivudine 24/48 1/151 Barbaro, 2001662.91 (1.04; 8.22)The rate of sustained response after interferon Alfa 2b+ lamivudine vs. lamivudine was increased by an increase in baseline inflammation scores
2.58 (0.88; 7.60)The rate of sustained response after interferon Alfa 2b+ lamivudine vs. lamivudine was not increased by an increase in baseline fibrosis scores
HBeAg loss Interferon Alfa 2b+ lamivudine vs. lamivudine 24/28 1/541 Perrillo, 20021042.34 (0.89; 6.16) The rate of HBeAg loss after interferon Alfa 2b+ lamivudine vs. lamivudine was not different among patients with baseline HAI scores 0–4
1.32 (0.67; 2.62) The rate of HBeAg loss after interferon Alfa 2b+ lamivudine vs. lamivudine was not different among patients with baseline HAI scores 5–9
0.79 (0.47; 1.32)The rate of HBeAg loss after interferon Alfa 2b+ lamivudine vs. lamivudine was not different among patients with baseline HAI scores >10
HBeAg loss Interferon Alfa 2b+lamivudine vs. interferon Alfa 2b 24/52 1/203 Perrillo, 20021040.88 (0.27; 2.91) No differences between interferon Alfa 2b+lamivudine vs. interferon Alfa 2b among patients with baseline HAI scores 0–4
0.92 (0.36; 2.39) No differences between interferon Alfa 2b+lamivudine vs. interferon Alfa 2b among patients with baseline HAI scores 5–9
1.61 (0.62; 4.21)No differences between interferon Alfa 2b+lamivudine vs. interferon Alfa 2b among patients with baseline HAI scores >10
Adjusted for treatment status odds ratio of sustained response: HBeAg seroconversion, HBV DNA disappearance and ALT normalization in HBeAg (+) patients. In HBeAg (-) patients: loss of HBV DNA, ALT normalization Peginterferon alfa-2a+lamivudine vs. lamivudine 9/15 1/160 Cindoruk, 2007115Presence of steatosis did not modify the effect of peginterferon alfa-2a + lamivudine vs. lamivudine on sustained response
14.97 (2.43; 92.28)The adjusted rates of sustained response were increased per increase in baseline Knodell HAI
Adjusted relative risk of flares defined as an increase in serum ALT to at least 3 times the baseline levelPeginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b52/781/310Flink, 20051202.00 (1.00; 4.00)Preexisting cirrhosis increased adjusted relative risk of flares
Adjusted relative risk of HBeAg seroconversion and HBV DNA 10,000 copies/mlPeginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b52/781/310Buster, 20071240.98 (0.17; 5.23)Presence of advanced fibrosis- fibrosis score of 4–6 (HAI) did not change adjusted relative risk of HBV DAN loss and HBeAg seroconversion
Baseline viral load at followup off the treatment
Negative HBV DNA with persistent HBeAgInterferon Alfa 2b vs. no treatment32/20–52w1/118Janssen, 1999831.87 (0.59; 5.87)no association between baseline positive HBV DNA (per 1 unit increase) and the effects of interferon Alfa 2b vs. no treatment
Loss of HBV DNA and HBeAg Interferon Alfa 2b vs. no treatment 24/24 1/169 Perrillo, 1990965.24 (1.22; 22.50)interferon Alfa 2b, 5MU/day vs. no treatment increased rates of HBV DNA and HBeAg loss among patients with baseline HBV DNA 2-99pg/ml. Random differences after interferon 1MU/day.
RR, random differences after interferon 1 or 5 MU/day among the patients with baseline HBV DNA 100–200 pg/ml or >200 pg/ml
HBeAg lossInterferon Alfa 2b vs. No treatment32/201/118Janssen, 1999833.18 (1.25; 8.05)RR, Interferon Alfa 2b, 10 MU three times per week vs. no treatments increased rates of HBeAg loss among the patients with baseline HBV DNA <10pg/ml. Random differences among the patients with baseline HBV DNA >10pg/ml
Loss of HBV DNA and HBeAg Interferon Alfa 2b+corticosteroid vs. no treatment 24/24 1/169 Perrillo, 1990965.38 (1.26; 22.84)interferon Alfa 2b+corticosteroid vs. no treatment increased rates of HBV and HBeAg loss among patients with baseline HBV DNA 2-99pg/ml
8.80 (0.49; 158.66) interferon Alfa 2b+corticosteroid vs. no treatment did not increase the rates of HBV DNA and HBeAg loss among patients with baseline HBV DNA 100–200 pg/ml
0.98 (0.06; 15.13)interferon Alfa 2b+corticosteroid vs. no treatment did not increase the rates of HBV DNA and HBeAg loss among patients with baseline HBV DNA >200 pg/ml
Loss of HBV DNA and HBeAgInterferon Alfa 2b+Corticosteroid vs. Interferon Alfa 2b24/241/169Perrillo, 199096Random differences after interferon Alfa 2b+Corticosteroid vs. interferon Alfa 2b in patients with baseline HBV DNA 2-99pg/ml, 100–200 pg/ml, or >200 pg/ml
HBeAg loss Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b 24/24 1/183 Wai, 20021021.10 (1.03; 1.17)Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b increased the rates of HBeAg loss in patients with low baseline HBV-DNA level
1.10 (1.01; 1.21)Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b increased the rates of HBeAg loss in patients with low baseline HBV-DNA and elevated baseline ALT
Odds ratio of sustained virologic responseInterferon Alfa 2b+lamivudine vs. lamivudine24/481/151Barbaro, 2001667.23 (2.71; 19.57)Odds of sustained suppression of serum levels of HBeAg and HBV DNA was significant in those with baseline viral load of 200 pg/ml or less independent of gender and age
HBeAg lossInterferon Alfa 2b+lamivudine vs. lamivudine52/241/75Sarin, 2005693.89 (1.20; 12.69)Interferon Alfa 2b+lamivudine vs. lamivudine resulted in increase rates of HBeAg loss in patients with baseline HBV DNA >107 copies/mL
HBeAg loss, HBeAg seroconversionInterferon Alfa 2b+lamivudine vs. lamivudine52/241/75Sarin, 2005694.87 (1.14; 20.74)Interferon Alfa 2b+lamivudine vs. lamivudine resulted in increase rates of HBeAg seroconversion and HBV DNA loss in patients with baseline HBV DNA >107 copies/mL
Viral breakthrough as the reappearance of serum HBV-DNA by solution hybridization assay in at least 2 consecutive tests during lamivudine therapy following the disappearance of the serum HBV DNAInterferon Alfa 2b+lamivudine vs. lamivudine176/1921/83Jang, 200465Random association with baseline HBV DNA levels (1 unit increase)
Adjusted for treatment status odds ratio of sustained response: HBeAg seroconversion, HBV DNA disappearance and ALT normalization in HBeAg (+) patients. In HBeAg (-) patients: loss of HBV DNA, ALT normalizationPeginterferon alfa-2a+lamivudine vs. lamivudine9/61/140Cindoruk, 20071151.05 (0.13; 8.14)Baseline mean viral load (copy/mL) was not associated with sustained response to the therapy
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a+lamivudine vs. lamivudine 48/24 1/76 Bonino, 20071142.24 (1.31; 3.83)Peginterferon alfa-2a+lamivudine vs. lamivudine increased sustained response among patients with baseline HBV DNA <6.12 log10 copies/ml
1.78 (1.11; 2.84)Peginterferon alfa-2a+lamivudine vs. lamivudine increased sustained response among patients with baseline HBV DNA >6.12–8.42 log 10 copies/ml
1.37 (0.67; 2.80)Peginterferon alfa-2a+lamivudine vs. lamivudine did not increase sustained response among patients with baseline HBV DNA >8.42 log 10 copies/ml
HBeAg seroconversion Peginterferon alfa-2a+lamivudine vs. lamivudine 48/24 1/543 Lau, 2005560.84 (0.47; 1.48) Peginterferon alfa-2a+lamivudine vs. lamivudine did not increase HBeAg seroconversion among patients with baseline HBV DNA levels ≤9.07 (log copies/ml)
1.91 (1.16; 3.15)Peginterferon alfa-2a+lamivudine vs. lamivudine increased HBeAg seroconversion among patients baseline HBV DNA levels >9.07–10.26 (log copies/ml)
2.01 (0.82; 4.90)Peginterferon alfa-2a+lamivudine vs. lamivudine did not increase HBeAg seroconversion among patients with baseline HBV DNA levels >10.26 (log copies/ml)
HBeAg seroconversion Peginterferon alfa-2a+lamivudine vs. peginterferon alfa-2a 48/24 1/542 Lau, 2005560.54 (0.32; 0.91) The rates of HBeAg seroconversion were lower after peginterferon alfa-2a+lamivudine vs. peginterferon alfa-2a among the patients with baseline HBV DNA levels ≤9.07 (log copies/ml)
1.03 (0.68; 1.54) Random differences among patients with baseline HBV DNA levels >9.07–10.26 (log copies/ml)
1.27 (0.59; 2.75)Random differences among patients with baseline HBV DNA levels>10.26 (log copies/ml)
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a+placebo vs. lamivudine 48/24 1/96 Bonino, 20071141.27 (0.71; 2.30) Random differences among patients with baseline HBV DNA <6.12 log10 copies/ml
3.87 (2.55; 5.88)Peginterferon alfa-2a+ placebo vs. lamivudine increased the rates of sustained response among patients with baseline HBV DNA >6.12–8.42 log 10 copies/ml
1.80 (0.91; 3.57)Random differences among patients with baseline HBV DNA >8.42 log 10 copies/ml
HBeAg seroconversion Peginterferon alfa-2a+placebo vs. lamivudine 48/24 1/543 Lau, 2005561.55 (0.95; 2.51) Random differences among patients with baseline HBV DNA levels ≤9.07 (log copies/ml)
1.86 (1.13; 3.08)Peginterferon alfa-2a+placebo vs. lamivudine increased rates of HBeAg seroconversion among patients with baseline HBV DNA levels >9.07–10.26 (log copies/ml)
1.58 (0.62; 4.01)Random differences among patients with baseline HBV DNA levels >10.26 (log copies/ml)
Adjusted odds ratios of sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/mlPeginterferon alfa-2a vs. lamivudine48/241/1036Bonino, 20071141.06 (0.93; 1.21)Baseline HBV DNA (Log10) was not associated with sustained response to therapy
Adjusted for treatment allocation, hepatitis B virus (HBV) genotype, baseline ALT odds ratio of persistent HBeAg loss at any time up to week 76 of post-treatment followupPeginterferon alfa-2b+lamivudine vs. lamivudine60/01/100Chan, 20061180.70 (0.38; 1.30)Baseline HBV DNA (log10) was not associated with sustained response to therapy
Adjusted for treatment allocation, HBV DNA genotype, IL-1b-511 polymorphism, baseline ALT odds ratio of persistent HBeAg loss and had less than 2 occasions with HBV DNA <100,000 copies/mL at any time up to week 76 of post-treatmentPeginterferon alfa-2b+lamivudine vs. lamivudine60/01/100Chan, 20061180.65 (0.35; 1.20)Baseline HBV DNA (log10) was not associated with sustained response to therapy
Adjusted odds ratio of sustained HBeAg lossPeginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b52/01/307Janssen, 2005781.60 (1.30; 1.80)Peginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b increased the rates of HBeAg loss among patients with low baseline viral load
Multivariate adjusted odds ratio of sustained combined response: HBeAg negative, HBV DNA <5 log10 copies/mL, and normal ALT levelPeginterferon alfa-2b vs. interferon Alfa 2b24/01/230Zhao, 2007810.53 (0.22; 1.28)Random difference among patients with baseline HBV DNA >8.1 vs. <8.1 log 10 copies/mL
Genotype, the outcomes at followup off the treatment
Adjusted for age, gender, baseline ALT, HBV DNA, and histology, precore G1896A mutation, core promoter A1762T, G1764A, and treatment with interferon with and without prednisone pretreatment odds ratios of antiviral response: as sustained clearance of serum HBV DNA Interferon Alfa 2b+corticosteroid vs. interferon Alfa 2b 24/0 1/115 Wai, 20021021.28 (1.06; 1.42)Patients with HBV genotype B vs. C had better sustained response to the therapy
1/68Wai, 20021021.47 (1.18; 1.82)Patients with HBV genotype B vs. C and elevated baseline ALT had better sustained response to the therapy
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a+lamivudine vs. lamivudine 48/24 1/126 Bonino, 20071142.09 (1.29; 3.40)Peginterferon alfa-2a+lamivudine vs. lamivudine increased the rates of sustained response among patients with genotype C
3.33 (1.53; 7.27)Peginterferon alfa-2a+lamivudine vs. lamivudine increased the rates of sustained response among patients with genotype D
HBeAg seroconversion Peginterferon alfa-2a+lamivudine vs. lamivudine 48/24 1/543 Lau, 2005561.34 (0.30; 5.92) Random difference among patients with HBV genotype A
1.42 (0.78; 2.58) Random difference among patients with HBV genotype B
1.49 (0.96; 2.31) Random difference among patients with HBV genotype C
0.67 (0.11; 3.97)Random difference among patients with HBV genotype D
HBeAg seroconversion Peginterferon alfa-2a+lamivudine vs. peginterferon alfa-2a 48/24 1/542 Lau, 2005560.33 (0.11; 1.02) Random difference among patients with HBV genotype A
1.04 (0.60; 1.80) Random difference among patients with HBV genotype B
0.86 (0.59; 1.25) Random difference among patients with HBV genotype C
1.00 (0.14; 7.05)Random difference among patients with HBV genotype D
Sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a+placebo vs. lamivudine 48/24 1/19 Bonino, 20071142.18 (0.27; 17.32) Random differences among patients with genotype A
1.14 (0.70; 1.85) Random differences among patients with genotype B
2.22 (1.36; 3.63)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of sustained response among patients with genotype C
1.47 (0.59; 3.69)Random differences among patients with genotype D
HBeAg seroconversion Peginterferon alfa-2a+placebo vs. lamivudine 48/24 1/543 Lau, 2005564.01 (1.15; 14.07)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with HBV genotype A
1.36 (0.74; 2.48) Random differences among patients with HBV genotype B
1.73 (1.13; 2.65)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with HBV genotype C
0.67 (0.11; 3.97)Random differences among patients with HBV genotype D
Adjusted odds ratios of sustained combined response: ALT normalization and an HBV DNA level of <20,000 copies/ml Peginterferon alfa-2a vs. lamivudine 48/24 1/1036 Bonino, 20071142.58 (0.73; 9.20) Random difference between genotypes (A vs. D)
3.69 (1.54; 8.79)Rates of sustained response were higher among patients with genotype B vs. D
5.46 (2.46; 12.10)Rates of sustained response were higher among patients with genotype C vs. D
Adjusted for treatment allocation, hepatitis B virus (HBV) genotype, baseline alanine aminotransferase and log HBV DNA odds ratio of persistent HBeAg loss at any time up to week 76 of post-treatment Peginterferon alfa-2b+lamivudine vs. lamivudine 60/24 1/100 Chan, 200611810.37 (1.11; 96.96)Rates of response were higher among patients with interleukin (IL)-1b-511 baseline genotype C/T vs. C/C
Random differences in patients with genotype C vs. B
Random differences in patients with Haplotype -511/-31 of interleukin (IL)-1b C-T vs. T-C
Random differences in patients with interleukin (IL)-1b-511 baseline genotype T/T vs. C/C
Random differences in patients with interleukin (IL)-1b-31 baseline genotype C/T vs. T/T or C/C vs. T/T
Random differences in patients with IL-1 receptor antagonist genotype IL-1RN 1/2 vs. 1/1
Random differences in patients with interleukin (IL)-1b-511 baseline genotype C/T and T/T vs. C/C
Random differences in patients with interleukin (IL)-1b-31 baseline genotype C/T and C/C vs. T/T
Adjusted relative risk of HBeAg seroconversion and HBV DNA 10,000 copies/ml. Peginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b 52/26 1/307 Buster, 200712411.30 (1.38; 92.57)adjusted rates of sustained response were higher among patients with genotype A vs. C
4.28 (1.39; 13.21)Adjusted rates of sustained response were higher among patients with genotype A vs. D
12.13 (1.24; 118.30) Adjusted rates of sustained response were higher among patients with genotype B vs. C
4.59 (1.14; 18.43)Adjusted rates of sustained response were higher among patients with genotype B vs. D
Adjusted odds ratio of sustained HBeAg loss Peginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b 52/26 1/307 Janssen, 2005782.40 (1.30; 4.60)Adjusted rates of sustained response were higher among patients with HBV genotype A vs. D
3.60 (1.40; 8.90)Adjusted rates of sustained response were higher among patients with HBV genotype A vs. C
2.20 (0.70; 7.00)Random difference among patients with HBV genotype B vs. C
Multivariate adjusted odds ratio of sustained combined response: HBeAg negative, HBV DNA <5 log 10 copies/mL, and normal ALT levelPeginterferon alfa-2b vs. interferon Alfa 2b24/240/250Zhao, 2007810.19 (0.08; 0.46)RR, genotype C vs. B
Previous treatment, outcomes at followup off the treatment
HBeAg seroconversion Peginterferon alfa-2a+lamivudine vs. lamivudine 48/24 1/543 Lau, 2005561.52 (1.08; 2.12)Rates of HBeAg seroconversion were higher among patients with no previous exposure to lamivudine
Random differences among those with previous LAM or Interferon therapy
HBeAg seroconversionPeginterferon alfa-2a + lamivudine vs. peginterferon alfa-2a48/241/542Lau, 200556Random differences among all patients with and without previous treatment
HBeAg seroconversion Peginterferon alfa-2a+placebo vs. lamivudine 48/24 1/543 Lau, 2005561.58 (1.11; 2.23)peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with no previous anti-HBV therapy
1.43 (0.55; 3.71) Random differences among patients with previous treatment: LAM
1.72 (1.24; 2.38)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with no previous exposure to lamivudine
3.26 (1.08; 9.88)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with previous treatment: IFN
1.55 (1.12; 2.14)Peginterferon alfa-2a+placebo vs. lamivudine increased the rates of HBeAg seroconversion among patients with no previous exposure to conventional interferon
HBeAg loss Peginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b 52/26 2/307 Janssen, 2005782.20 (1.10; 4.50)Peginterferon alfa-2b+lamivudine vs. peginterferon alfa-2b increased the rates of HBeAg loss among patients without previous interferon therapy
Flink, 20061210.94 (0.63; 1.40) Random differences among naïve to any treatments patients
1/307Flink, 2006121Random differences among patients with previous IFN, LAM, and combined therapy
HBV DNA loss, normalization of ALTRandom differences among patients naïve to any antiviral treatment

From: Appendix E Tables and Figures

Cover of Management of Chronic Hepatitis B
Management of Chronic Hepatitis B.
Evidence Reports/Technology Assessments, No. 174.
Wilt TJ, Shamliyan T, Shaukat A, et al.

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