Immunoglobulins for preventing hepatitis A

  • Review
  • Intervention




Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.


To assess the beneficial and harmful effects of the pre- and post-exposure prophylaxis with immunoglobulins for preventing hepatitis A.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, The Chinese Biomedical Database, and Science Citation Index Expanded for trials until October 2008. In addition, we read through reference lists of the identified publications and handsearched three journals.

Selection criteria

Randomised clinical trials on immunoglobulin prophylaxis for preventing hepatitis A, irrespective of blinding, publication status, or language.

Data collection and analysis

Data were extracted by two authors and verified by a third author. Results were presented as relative risks (RR) with 95% confidence intervals (CI). The primary outcome was occurrence of hepatitis A (infectious hepatitis).

Main results

We included 13 trials with 567,476 participants randomised to pre- or post-exposure prophylaxis. The trials had high risk of bias. The trials were heterogeneous in terms of study setting, participants, interventions, and outcome measures. Our meta-analysis with six randomised trials showed that immunoglobulins, when used for pre-exposure prophylaxis, significantly reduced the number of adult patients with hepatitis A at 6 to 12 months (1020/286503 versus 761/134529; RR 0.53; 95% CI 0.40 to 0.70; random-effects model) in comparison with no intervention or inactive control. Four trials showed a similar effect in children aged 3 to 17 at 6 to 12 months follow-up (917/210822 versus 677/78960; RR 0.45; 95% CI 0.34 to 0.59). Comparing different doses of immunoglobulins, higher dosage was generally more effective than lower dosage (1.5 ml better than 0.75 ml and 0.75 ml better than 0.1 ml) in preventing hepatitis A. No significant systemic adverse events were reported. One trial showed that immunoglobulin was more effective than placebo for post-exposure prophylaxis. It appeared that there was no significant difference between immunoglobulins and inactivated hepatitis A vaccine in seroconversion to hepatitis A vaccine antibodies at four weeks (RR 1.16; 95% CI 0.98 to 1.38), but immunoglobulins were significantly less effective than vaccine regarding antibody levels at 8, 12, or 24 weeks.

Authors' conclusions

Immunoglobulins seem to be effective for pre-exposure and post-exposure prophylaxis of hepatitis A. However, caution is warranted for the positive findings due to the limited number of trials, year of conductance, and risk of bias. Conductance of rigorous trials will be justifiable.




甲型肝炎 (傳染性肝炎) 是一種常見的區域性流行病。使用被動免疫方法中的免疫球蛋白作為進行預防的方法。




我們搜尋截至2008年10月的The Cochrane HepatoBiliary Group Controlled Trials Register, Cochrane library的The Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、 EMBASE、 The Chinese Biomedical Database和Science Citation Index Expanded。 此外我們閱覽了已找出的發表刊物的參考文獻清單,並且手動搜索三份期刊。




兩位作者提取資料,第3位作者驗證資料。結果表示為相對風險 (RR) ,95% 信賴區間 (CI)。主要結果是指甲型肝炎的發病率 (傳染性肝炎)。


我們收錄了13個隨機試驗,共有567,476位受試者隨機參加暴露前或暴露後預防。 試驗具有較高的誤差風險。 從研究背景、受試者、介入和結果測量值方面來看,研究具有異質性。我們對6個隨機試驗實施 metaanalysis, 指出和無干預法或無活性控制組相比,如果甲型肝炎暴露前使用免疫球蛋白預防,在6 – 12個月期間可以明顯降低甲型肝炎的成年人病人的比例(1020/286503 對照761/134529; RR 0.53; 95% CI 0.40 0.70; 隨機效果模式) 。4個試驗在3 – 17歲的兒童以及6 – 12個月的追蹤方面得到類似的結果(917/210822 對照677/78960; RR 0.45;95% CI 0.34 0.59)。比較不同劑量的免疫球蛋白,高劑量比低劑量更有效預防甲型肝炎(1.5 ml 比0.75 ml 更有效,0.75 ml 比0.1 ml 更有效)。沒有報導有顯著的系統性不良反應。1個試驗指出,免疫球蛋白比安慰劑更能有效使用於暴露後預防。4周內,似乎免疫球蛋白,以及經過血清轉化成甲型肝炎疫苗抗體的無活性甲型肝炎疫苗並沒有顯著差異 (RR 1.16; 95% CI 0.98 1.38), 但是第8周,12周,24周,在抗體濃度方面,免疫球蛋白明顯不如疫苗有效。


免疫球蛋白似乎能夠有效的在暴露前後預防甲型肝炎。 但是,必須謹慎對待這些正面的發現,因為試驗的人數和進行年數有限,存在偏誤風險。未來應進行較嚴謹的試驗以茲證明。


此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


甲型肝炎是常發生在低收入國家的一種傳染性病毒疾病。甲型肝炎主要由糞口傳染依賴手足口在人們之間傳播。 在沒有研發出甲型肝炎疫苗(主動免疫)之前,使用被動免疫方法中的免疫球蛋白配方治療甲型肝炎是一種重要的預防措施。本次回顧總結免疫球蛋白似乎在兒童和成年人中間有效預防甲型肝炎。但是,此結論的依據並不如包含的試驗那麼具有可信度,因為試驗存在誤差風險,而且數量不足。因為,免疫球蛋白配方潛在具有引起血液傳染疾病的風險,例如,人類免疫缺乏病毒, 而且,因為使用甲型肝炎疫苗的關係,人們較少使用免疫球蛋白。但是,某些特殊族群還是需要使用免疫球蛋白,例如,免疫系統較弱的人群、一歲以內的兒童、對疫苗免疫沒有做出完整回應的人群等。未來需要實施臨床試驗來說明免疫球蛋白在這些人群中使用的利弊。

Plain language summary

Immunoglobulins (human serum immune gamma globulins) seem effective for prevention of hepatitis A

Hepatitis A is a common, contagious viral disease in low-income countries. Hepatitis A is transmitted primarily by faecal-oral spread from person to person. Passive immunoprophylaxis for hepatitis A using immunoglobulin preparations were essential for prevention before development of specific hepatitis A vaccine (active immunisation). This review concludes that immunoglobulins seem effective for preventing hepatitis A in both children and adults. However, the evidence, on which the conclusion is based, is not strong as the included trials appear to have risk of bias and their number is insufficient. Because there is a potential risk of blood-borne diseases from immunoglobulins preparations, such as human immunodeficiency virus, and because of the availability of hepatitis A vaccine, the use of immunoglobulins has become limited. However, their use is still required in some specific populations, such as persons with compromised immune function, children under one year of age, or persons who have not developed a full response to vaccine immunisation. Future clinical trials should address the benefit and harm of immunoglobulins in these populations.