Summary of findings for the main comparison.
Hepatitis A vaccines for preventing clinical hepatitis A in those not previously exposed
| Hepatitis A vaccines for preventing hepatitis A in those not previously exposed | ||||||
| Patient or population: patients with preventing hepatitis A. Settings: pre‐exposure. Intervention: hepatitis A vaccines. | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | Number of participants (trials) | Quality of the evidence (GRADE) | Comment | |
| Assumed risk | Corresponding risk | |||||
| Control | Hepatitis A vaccines | |||||
| Clinically apparent hepatitis A (low risk of bias trials) Dienstag 1999 Follow‐up: 12 to 17 months | 4 per 1000 | 4 per 1000 (0 to 1) | RR 0.09 (0.03 to 0.30) | 41430 (3 studies) | ⊕⊕⊕⊕ high | |
| Clinically apparent hepatitis A (all included trials) Dienstag 1999 Follow‐up: 1 to 60 months | 1 per 1000 | 0 per 1000 (0 to 0) | RR 0.09 (0.05 to 0.17) | 732380 (9 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (inactivated HAV vaccines) low risk of bias trials Dienstag 1999 Follow‐up: 12 to 17 months | 4 per 1000 | 0 per 1000 (0 to 1) | RR 0.09 (0.03 to 0.30) | 41430 (3 studies) | ⊕⊕⊕⊕ high | |
| Clinically apparent hepatitis A (inactivated HAV vaccines) all included trials Dienstag 1999 Follow‐up: 12 to 17 months | 5 per 1000 | 1 per 1000 (0 to 1) | RR 0.12 (0.05 to 0.31) | 41690 (4 studies) | ⊕⊕⊝⊝ low | |
| Clinically apparent hepatitis A (live attenuated HAV vaccines) low risk of bias Dienstag 1999 | See comments | See comments | No included inactivated HAV vaccine study was at low risk of bias. | |||
| Clinically apparent hepatitis A (live attenuated HAV vaccines) all included trials Dienstag 1999 Follow‐up: 1 to 60 months | 1 per 1000 | 0 per 1000 (0 to 0) | RR 0.07 (0.03 to 0.17) | 690690 (5 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (Dose of live attenuated HAV vaccine, titre >= TCID50 ) low risk of bias Dienstag 1999 | See comment | See comment | No included inactivated HAV vaccine study was at low risk of bias. | |||
| Clinically apparent hepatitis A (Dose of live attenuated HAV vaccine, titre >= TCID50 ) all included trials Dienstag 1999 Follow‐up: 24 to 60 months | 9 per 1000 | 0 per 1000 (0 to 1) | RR 0.03 (0.02 to 0.06) | 62270 (2 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (Dose of live attenuated HAV vaccine, titre < TCID50 ) low risk of bias Dienstag 1999 | See comment | See comment | No included inactivated HAV vaccine study was at low risk of bias. | |||
| Clinically apparent hepatitis A (Dose of live attenuated HAV vaccine, titre < TCID50 ) all included trials Dienstag 1999 Follow‐up: 1 to 36 months | 0 per 1000 | 0 per 1000 (0 to 0) | RR 0.11 (0.05 to 0.26) | 628420 (3 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (low endemicity) low risk of bias Dienstag 1999 Follow‐up: 12 months | 71 per 1000 | 14 per 1000 (6 to 31) | RR 0.19 (0.08 to 0.42) | 1037 (1 study) | ⊕⊕⊕⊕ high | |
| Clinically apparent hepatitis A (low endemicity) all included trials Dienstag 1999 Follow‐up: 12 months | 71 per 1000 | 14 per 1000 (6 to 30) | RR 0.19 (0.08 to 0.42) | 1037 (1 study) | ⊕⊕⊕⊕ high | |
| Clinically apparent hepatitis A (high endemicity) low risk of bias Dienstag 1999 Follow‐up: 15 to 17 months | 3 per 1000 | 0 per 1000 (0 to 0) | RR 0.05 (0.01 to 0.17) | 40393 (2 studies) | ⊕⊕⊕⊕ high | |
| Clinically apparent hepatitis A (high endemicity) all included trials Dienstag 1999 Follow‐up: 1 to 60 months | 1 per 1000 | 1 per 1000 (0 to 0) | RR 0.08 (0.04 to 0.15) | 731343 (8 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (single dose regimen) low risk of bias Dienstag 1999 Follow‐up: 15 months | 124 per 1000 | 4 per 1000 (0 to 58) | RR 0.03 (0 to 0.47) | 274 (1 study) | ⊕⊕⊕⊕ high | |
|
Clinically apparent hepatitis A (single dose regimen) all included studies Dienstag 1999 Follow‐up: 1 to 60 months |
1 per 1000 | 0 per 1000 (0 to 0) | RR 0.07 (0.03 to 0.15) | 690707 (6 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (multiple doses) low risk of bias Dienstag 1999 Follow‐up: 12 to 17 months | 4 per 1000 | 0 per 1000 (0 to 1) | RR 0.11 (0.03 to 0.40) | 41156 (2 studies) | ⊕⊕⊕⊕ high | |
|
Clinically apparent hepatitis A (multiple doses) all included trials Dienstag 1999 Follow‐up: 12 to 17 months |
4 per 1000 | 1 per 1000 (0 to 1) | RR 0.14 (0.05 to 0.37) | 41416 (3 studies) | ⊕⊕⊕⊝ moderate | |
| Clinically apparent hepatitis A (follow‐up duration 1 to 12 months) low risk of bias Dienstag 1999 Follow‐up: 12 months | 71 per 1000 | 14 per 1000 (6 to 30) | RR 0.19 (0.08 to 0.42) | 1037 (1 study) | ⊕⊕⊕⊕ high | |
|
Clinically apparent hepatitis A (follow‐up duration 1 to 12 months) all included trials Dienstag 1999 Follow‐up: 1 to 12 months |
47 per 1000 | 9 per 1000 (5 to 17) | RR 0.20 (0.1 to 0.37) | 2377 (3 studies) | ⊕⊝⊝⊝ very low | |
|
Clinically apparent hepatitis A (follow‐up duration 13 to 24 months) low risk of bias Dienstag 1999 Follow‐up: 15 to 17 months |
3 per 1000 | 0 per 1000 (0 to 0) | RR 0.05 (0.01 to 0.17) | 40393 (2 studies) | ⊕⊕⊕⊕ high | |
|
Clinicially apparent hepatitis A (follow‐up duration 13 to 24 months) all included trials Dienstag 1999 Follow‐up: 15 to 24 months |
4 per 1000 | 0 per 1000 (0 to 1) | RR 0.06 (0.02 to 0.17) | 164776 (4 studies) | ⊕⊝⊝⊝ very low | |
| Clinically apparent hepatitis A (follow‐up duration 25 to 48 months) low risk of bias | See comments | See comments | Insufficients evidence | |||
|
Clinicially apparent hepatitis A (follow‐up duration 25 to 48 months) all included trials Dienstag 1999 Follow‐up: 36 months |
0 per 1000 (0 to 0) | RR 0.05 (0.02 to 0.13) | 564642 (1 study) | ⊕⊕⊝⊝ low | ||
| Clinically apparent hepatitis A (follow‐up duration 49 to 60 months) low risk of bias | See comments | See comments | Insufficient evidence | |||
|
Clinically apparent hepatitis A (follow‐up duration 49 to 60 months) all included trials Dienstag 1999 Follow‐up: 60 months |
67 per 1000 | 4 per 1000 (1 to 27) | RR 0.06 (0.01 to 0.41) | 585 (1 study) | ⊕⊕⊝⊝ low | |
|
All‐cause mortality low risk of bias Mortality Follow‐up: 17 months |
0 per 1000 (0 to 2) | RR 1.40 (0.62 to 3.16) | 585 (1 study) | ⊕⊕⊕⊕ high | ||
|
All‐cause mortality all included trials Mortality Follow‐up: 17 months |
0 per 1000 (0 to 2) | RR 1.40 (0.62 to 3.16) | 585 (1 study) | ⊕⊕⊕⊕ high | ||
| Hepatitis A‐related mortality | See comment | See comment | No trial directly addressed this as an outcome. | |||
| Lack of sero‐protection, (anti HAV IgG < 10mIU/L) (low risk of bias) Maiwald 1997 Follow‐up: 12 to 17 months | See comment | See comment | No study included this outcome. | |||
| Lack of sero‐protection, (anti HAV IgG < 10mIU/L) (all included trials) Maiwald 1997 Follow‐up: 12 to 17 months | See comment | See comment | No study included this outcome. | |||
| Lack of sero‐protection, (anti HAV IgG < 20mIU/L) (low risk of bias ) Maiwald 1997 Follow‐up: 17 months | 972 per 1000 | 10 per 1000 (0 to 29) | RR 0.01 (0.00 to 0.03) | 486 (1 study) | ⊕⊕⊕⊕ high | |
| Lack of sero‐protection, (anti HAV IgG < 20mIU/L) (all included trials) Maiwald 1997 Follow‐up: 12 to 17 months | 973 per 1000 | 10 per 1000 (0 to 29) | RR 0.01 (0 to 0.03) | 739 (2 studies) | ⊕⊕⊝⊝ low | |
| Non‐serious local adverse events (low risk of bias) inactivated HAV vaccine ICH‐GCP 1997 Follow‐up: 12 to 15 months | 85 per 1000 | 101 per 1000 (57 to 179) | RR 1.19 (0.67 to 2.11) | 1299 (2 studies) | ⊕⊕⊕⊕ high | |
| Non‐serious local adverse events (all included trials) ICH‐GCP 1997 Follow‐up: 12 to 15 months | 98 per 1000 | 118 per 1000 (84 to 166) | RR 1.21 (0.86 to 1.70) | 1559 (4 studies) | ⊕⊕⊝⊝ low | |
| Non‐serious systemic adverse events (low risk of bias) inactivated HAV vaccine ICH‐GCP 1997 Follow‐up: 12 to 15 months | 42 per 1000 | 45 per 1000 (28 to 74) | RR 1.09 (0.67 to 1.78) | 1299 (3 studies) | ⊕⊕⊕⊕ high | |
|
Non‐serious systemic adverse events (all included studies) inactivated HAV vaccine
ICH‐GCP 1997 Follow‐up: 12 to 15 months |
65 per 1000 | 64 per 1000 (45 to 92) | RR 0.98 (0.68 to 1.41) | 1599 (4 studies) | ⊕⊕⊝⊝ low | |
| Non‐serious local adverse events (low risk of bias) live attenuated HAV vaccine ICH‐GCP 1997 | See comment | See comment | Insufficient evidence | |||
| Non‐serious local adverse events (all included studies) live attenuated HAV vaccine ICH‐GCP 1997 | See comment | See comment | Insufficient evidence | |||
| Non‐serious systemic adverse events (low risk of bias) live attenuated HAV vaccine ICH‐GCP 1997 Follow‐up: 12 to 17 months | See comment | See comment | Insufficient evidence | |||
| Non‐serious systemic adverse events (all included studies) live attenuated HAV vaccine ICH‐GCP 1997 | See comment | See comment | Insufficient evidence | |||
| *The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||