Efficacy and safety of interferon based antiviral therapy for children with hepatitis B: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHENG Daxin ^1,2 , LIU Yi ^2,3 , XU Liran ² , YU Qingqing ² ,  ZHAO Sihai ²

1. Division of Neonatology, Shanxi Provincial People’s Hospital, Xi’an, 710068, P.R.China;
2. Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, Xi’an Jiaotong University, Xi’an, 710061, P.R.China;
3. Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, P.R.China;

Corresponding author：

ZHAO Sihai, Email: sihaizhao@xjtu.edu.cn

Keywords：

Children; Hepatitis B; Efficacy; Safety; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.201704051

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Objective To systematically review the efficacy and safety of interferon based antiviral therapy for children with hepatitis B. Methods PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials (RCTs) of interferon based antiviral therapy for children with hepatitis B from inception to December 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 studies involving 723 patients were included. The results of meta-analysis showed that: follow-up <12 months, the virological response rate (RR=2.82, 95%CI 1.98 to 4.02, P<0.000 01), serum HBeAg clearance rate (RR=3.02, 95%CI 1.95 to 4.67,P<0.000 01) and ALT normalization rate (RR=1.42, 95%CI 1.19 to 1.70,P=0.000 1) were significantly higher in the interferon group than the control group. Follow-up >12 months, the virological response rate (RR=1.75, 95%CI 1.18 to 2.60, P=0.006) and serum HBeAg clearance rate (RR=2.17, 95%CI 1.28 to 3.65, P=0.004) were also significantly higher in the interferon group. Severe adverse effects were not reported in included studies. Conclusion Current evidence shows that higher virological response is found in HBV infected children with interferon treatment. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

Citation： CHENG Daxin, LIU Yi, XU Liran, YU Qingqing, ZHAO Sihai. Efficacy and safety of interferon based antiviral therapy for children with hepatitis B: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(11): 1298-1304. doi: 10.7507/1672-2531.201704051 Copy

1.	Lok AS, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children. Hepatology, 1988, 8(5): 1130-1133.
2.	Jonas MM, Lok AS, McMahon BJ, et al. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis. Hepatology, 2016, 63(1): 307-318.
3.	Livingston SE, Simonetti JP, McMahon BJ, et al. Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis, 2007, 195(1): 5-11.
4.	Yao GB. Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China. Gut, 1996, 38(Suppl 2): 39-42.
5.	Zhang HW, Yin JH, Li YT, et al. Risk factors for acute hepatitis B and its progression to chronic hepatitis in Shanghai, China. Gut, 2008, 57(12): 1713-1720.
6.	Barbera C, Bortolotti F, Crivellaro C, et al. Recombinant interferon-alpha 2a hastens the rate of HBeAg clearance in children with chronic hepatitis B. Hepatology, 1994, 20(2): 287-290.
7.	陈益平, 张桂莲, 陈一华, 等. 重组 α-2b 干扰素治疗儿童慢性乙型肝炎疗效观察. 中国实用儿科杂志, 2000, 15(1): 43-44.
8.	Gregorio GV, Jara P, Hierro L, et al. Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. Hepatology, 1996, 23(4): 700-707.
9.	Lai CL, Lok AS, Lin HJ, et al. Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children. Lancet, 1987, 2(8564): 877-880.
10.	Lai CL, Lin HJ, Lau JN, et al. Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children. Q J Med, 1991, 78(286): 155-163.
11.	陆坚, 杨山麦, 敖飞健, 等. 干扰素治疗慢性乙型肝炎 43 例. 实用儿科临床杂志, 1999, 14(1): 3-4.
12.	Ruiz Moreno M, Jimenez J, Porres JC, et al. A controlled trial of recombinant interferon-alpha in Caucasian children with chronic hepatitis B. Digestion, 1990, 45(1): 26-33.
13.	Ruiz Moreno M, Rua MJ, Molina J, et al. Prospective, randomized controlled trial of interferon-alpha in children with chronic hepatitis B. Hepatology, 1991, 13(6): 1035-1039.
14.	Sokal EM, Conjeevaram HS, Roberts EA, et al. Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial. Gastroenterology, 1998, 114(5): 988-995.
15.	Utili R, Sagnelli E, Galanti B, et al. Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study. Am J Gastroenterol, 1991, 86(3): 327-330.
16.	Vajro P, Tedesco M, Fontanella A, et al. Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection. Pediatr Infect Dis J, 1996, 15(3): 223-231.
17.	张静. 重组人干扰素 α-2b 注射液治疗儿童慢性乙型肝炎疗效分析. 中国实用医药, 2015, 10(2): 118-119.
18.	Yu HB, Liu EQ, Lu SM, et al. Treatment with peginterferon versus interferon in Chinese patients with hepatitis B. Biomed Pharmacother, 2010, 64(8): 559-564.

1. Lok AS, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children. Hepatology, 1988, 8(5): 1130-1133.
2. Jonas MM, Lok AS, McMahon BJ, et al. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis. Hepatology, 2016, 63(1): 307-318.
3. Livingston SE, Simonetti JP, McMahon BJ, et al. Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis, 2007, 195(1): 5-11.
4. Yao GB. Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China. Gut, 1996, 38(Suppl 2): 39-42.
5. Zhang HW, Yin JH, Li YT, et al. Risk factors for acute hepatitis B and its progression to chronic hepatitis in Shanghai, China. Gut, 2008, 57(12): 1713-1720.
6. Barbera C, Bortolotti F, Crivellaro C, et al. Recombinant interferon-alpha 2a hastens the rate of HBeAg clearance in children with chronic hepatitis B. Hepatology, 1994, 20(2): 287-290.
7. 陈益平, 张桂莲, 陈一华, 等. 重组 α-2b 干扰素治疗儿童慢性乙型肝炎疗效观察. 中国实用儿科杂志, 2000, 15(1): 43-44.
8. Gregorio GV, Jara P, Hierro L, et al. Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. Hepatology, 1996, 23(4): 700-707.
9. Lai CL, Lok AS, Lin HJ, et al. Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children. Lancet, 1987, 2(8564): 877-880.
10. Lai CL, Lin HJ, Lau JN, et al. Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children. Q J Med, 1991, 78(286): 155-163.
11. 陆坚, 杨山麦, 敖飞健, 等. 干扰素治疗慢性乙型肝炎 43 例. 实用儿科临床杂志, 1999, 14(1): 3-4.
12. Ruiz Moreno M, Jimenez J, Porres JC, et al. A controlled trial of recombinant interferon-alpha in Caucasian children with chronic hepatitis B. Digestion, 1990, 45(1): 26-33.
13. Ruiz Moreno M, Rua MJ, Molina J, et al. Prospective, randomized controlled trial of interferon-alpha in children with chronic hepatitis B. Hepatology, 1991, 13(6): 1035-1039.
14. Sokal EM, Conjeevaram HS, Roberts EA, et al. Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial. Gastroenterology, 1998, 114(5): 988-995.
15. Utili R, Sagnelli E, Galanti B, et al. Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study. Am J Gastroenterol, 1991, 86(3): 327-330.
16. Vajro P, Tedesco M, Fontanella A, et al. Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection. Pediatr Infect Dis J, 1996, 15(3): 223-231.
17. 张静. 重组人干扰素 α-2b 注射液治疗儿童慢性乙型肝炎疗效分析. 中国实用医药, 2015, 10(2): 118-119.
18. Yu HB, Liu EQ, Lu SM, et al. Treatment with peginterferon versus interferon in Chinese patients with hepatitis B. Biomed Pharmacother, 2010, 64(8): 559-564.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of interferon based antiviral therapy for children with hepatitis B: a meta-analysis

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