国产聚乙二醇化干扰素α治疗HBeAg阳性慢性乙型肝炎患者疗效研究
|
摘要
目的观察国产聚乙二醇化干扰素α-2b(peg-IFN-α-2b)治疗血清HBe Ag阳性的慢性乙型肝炎(CHB)患者的效果。方法 2015年1月～2017年12月纳入血清HBe Ag阳性的CHB患者500例,被分为A组150例,给予国产peg-IFN-α-2b治疗,和B组350例,给予peg-IFN-α-2a治疗。两组均治疗24～48 w。在治疗结束后,随访24 w。结果治疗前,A组血清HBV DNA定量为(6.1±0.7) lg cps/ml、谷丙转氨酶(ALT)为(81.1±29.8)u/l、体质指数为(22.1±2.9)、血清HBe Ag定量为(3.1±0.6) lg s/co和HBs A定量为(4.4±0.6) IU/ml,与B组的(6.2±0.67) lg cps/ml、(80.7±27.9) U/L、(21.9±2.9)、(3.1±0.1) lg s/co和(4.4±0.5) IU/ml比,差异均无统计学意义(P>0.05);在随访24 w结束时,A组血清ALT复常率为64.0%,血清HBV DNA阴转率为60.0%,与B组的66.9%和62.9%比,差异均无统计学意义(P>0.05);两组不良反应发生率也无显著性相差(P>0.05)。结论应用国产peg-IFN-α-2b治疗血清HBe Ag阳性的CHB患者能获得与peg-IFN-α-2a治疗相似的疗效,但价格便宜,具有临床应用价值。
Objectives To investigate the efficacy of domestic pegylated interferonα-2 b(peg-IFN-α-2 b) in treatment of patients with serum HBeAg positive chronic hepatitis B(CHB). Methods 500 patients with serum HBeAg positive CHB were recruited in this study between January 2015 and December 2017,and 150 patients in group A were treated by domestic peg-IFN-α-2 b,and 350 patients in group B received peg-IFN-α-2 a. The regimen lasted for 24 to 48 weeks,and all patients with CHB were followed-up for 24 weeks. Results At presentation,serum HBV DNA loads,serum alanine aminotransferase(ALT) level,body mass index,serum HBeAg and HBsAg levels in group A were(6.1±0.7) lg cps/ml,(81.1±29.8) U/L,(22.1±2.9),(3.1±0.6) lg s/co and(4.4±0.6) IU/ml,without significantly different as compared to(6.2±0.67) lg cps/ml,(80.7±27.9) u/l,(21.9±2.9),(3.1±0.1) lg s/co and(4.4±0.5) IU/ml in group B(P>0.05);at the end of 24 week follow-up,serum ALT normalization rate and serum HBV DNA loss in group A were 64.0% and 60.0%,also no significantly different as compared to66.9% and 62.9% in group B(P>0.05);the side effects during the antiviral treatment in the two groups were not significantly different(P>0.05). Conclusion The application of domestic peg-IFN-α-2 b in treatment of patients with serum HBeAg-positive CHB might get the same viralogic and biochemical responses,and the regimen is safe and cheap,which warrants further clinical investigation.
Objectives To investigate the efficacy of domestic pegylated interferonα-2 b(peg-IFN-α-2 b) in treatment of patients with serum HBeAg positive chronic hepatitis B(CHB). Methods 500 patients with serum HBeAg positive CHB were recruited in this study between January 2015 and December 2017,and 150 patients in group A were treated by domestic peg-IFN-α-2 b,and 350 patients in group B received peg-IFN-α-2 a. The regimen lasted for 24 to 48 weeks,and all patients with CHB were followed-up for 24 weeks. Results At presentation,serum HBV DNA loads,serum alanine aminotransferase(ALT) level,body mass index,serum HBeAg and HBsAg levels in group A were(6.1±0.7) lg cps/ml,(81.1±29.8) U/L,(22.1±2.9),(3.1±0.6) lg s/co and(4.4±0.6) IU/ml,without significantly different as compared to(6.2±0.67) lg cps/ml,(80.7±27.9) u/l,(21.9±2.9),(3.1±0.1) lg s/co and(4.4±0.5) IU/ml in group B(P>0.05);at the end of 24 week follow-up,serum ALT normalization rate and serum HBV DNA loss in group A were 64.0% and 60.0%,also no significantly different as compared to66.9% and 62.9% in group B(P>0.05);the side effects during the antiviral treatment in the two groups were not significantly different(P>0.05). Conclusion The application of domestic peg-IFN-α-2 b in treatment of patients with serum HBeAg-positive CHB might get the same viralogic and biochemical responses,and the regimen is safe and cheap,which warrants further clinical investigation.
引文
[1]Feng H,Yin J,Han Y P,et al.Sustained changes of Treg and Th17 cells during interferon-αtherapy in patients with chronic hepatitis B.Viral Immunol,2015,28(8):412-417.
[2]Zhao XL,Yang JR,Lin SZ,et al.Serum viral duplex-linear DNAproportion increases with the progression of liver disease in patients infected with HBV.Gut,2016,65(3):502-511.
[3]Yang L,Lu M.Small molecule inhibitors of hepatitis B virus nucleocapsid assembly:a new approach to treat chronic HBVinfection.Curr Medl Chem,2017,24(7)802-813.
[4]丁振苗,吴茂盛,叶泽兵,等.Peg-IFN-α-2b联合阿德福韦酯治疗HBe Ag阳性慢性乙型肝炎疗效分析.实用肝脏病杂志,2012,15(5):442-443.
[5]Suh DJ,Lee HC,Byun KS,et al.Efficacy and safety of pegylated interferon-α2a in patients with lamivudine-resistant HBe Ag-positive chronic hepatitis B.Antivi Ther,2013,18(6):765-773.
[6]封波,尚佳,武淑环,等.Y型聚乙二醇干扰素α-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究.实用肝脏病杂志,2017,20(3):284-289.
[7]Turnes J,Romero-Gómez M,Planas R,et al.Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain.Gastroenterol Hepatol,2013,36(9):555-564.
[8]中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[9]Suh DJ,Lee HC,Byun KS,et al.Efficacy and safety of pegylated interferon-α2a in patients with lamivudine-resistant HBe Agpositive chronic hepatitis B.Antivir Ther,2013,18(6):765-773.
[10]Ning Q,Han M,Sun Y,et al.Switching from entecavir to Peg IFNalfa-2a in patients with HBe Ag-positive chronic hepatitis B:Arandomi sed open-label trial(OSST trial).J Hepatol,2014,61(4):777-784.
[11]Jie Y,Li X,Lin G,et al.Real-life practice of antiviral therapy and disease patterns of patients with chronic hepatitis B:a single-center retrospective observation study.Hepatol Int,2014,8(4):501-507.
[12]Wong GLH,Yiu KKL,Wong VWS,et al.Meta-analysis:reduction in hepatic events following interferon-alfa therapy of chronic hepatitis B.Aliment Pharmacol Ther,2010,32(9):1059-1068.
[13]贾妮娜,林兰意,郭斯敏,等.长效干扰素α-2a治疗慢性乙型肝炎过程中外周血浆样树突状细胞的变化及其与疗效的关系.中华肝脏病杂志,2015,23(1):34-39.
[14]封波,尚佳,武淑环,等.聚乙二醇干扰素α-2b(Y型,40k D)注射液治疗基因1/6型慢性丙型肝炎患者的疗效和安全性分析.中华肝脏病杂志,2017,25(3):187-194.
[15]Miyase S,Morishita Y,Haraoka K,et al.1142 Peg-IFNα-2a plus ribavirin shows higher SVR rate compare with pegIFNa-2b plus ribavirin in elder patients with chronic hepatitis C specially in IL-28B major allele.J Hepatol,2012,56(Suppl 2):S451-S451.
[16]Karabay O,Tuna N,Esen S,et al.Comparative efficacy of pegylated interferonsα-2a and 2b in the treatment of HBe Agnegative chronic hepatitis B infection.Eur J Gastroenterol Hepatol,2012,24(11):1296-1301.
[17]Dogan UB,Golge N,Akin MS.The comparison of the efficacy of pegylated interferonα-2a andα-2b in chronic hepatitis Bpatient].Eur J Gastroenterol Hepatol,2013,25(9):1312-1316.
[18]Thompson AJ,Colledge D,Rodgers S,et al.Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro.Antivir Ther,2009,14(6):797-808.
[19]Ferns RB,Naoumov NV,Gilson RJ,et al.Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBe Ag loss.J Clini Virol,2007,39(3):199-204.
[20]侯凤琴,尹亚琳,曾玲英,等.聚乙二醇干扰素α-2b(Y型,40k D)注射液治疗HBe Ag阳性慢性乙型肝炎患者的疗效和安全性分析.中华肝脏病杂志,2017,25(8)589-596.
[2]Zhao XL,Yang JR,Lin SZ,et al.Serum viral duplex-linear DNAproportion increases with the progression of liver disease in patients infected with HBV.Gut,2016,65(3):502-511.
[3]Yang L,Lu M.Small molecule inhibitors of hepatitis B virus nucleocapsid assembly:a new approach to treat chronic HBVinfection.Curr Medl Chem,2017,24(7)802-813.
[4]丁振苗,吴茂盛,叶泽兵,等.Peg-IFN-α-2b联合阿德福韦酯治疗HBe Ag阳性慢性乙型肝炎疗效分析.实用肝脏病杂志,2012,15(5):442-443.
[5]Suh DJ,Lee HC,Byun KS,et al.Efficacy and safety of pegylated interferon-α2a in patients with lamivudine-resistant HBe Ag-positive chronic hepatitis B.Antivi Ther,2013,18(6):765-773.
[6]封波,尚佳,武淑环,等.Y型聚乙二醇干扰素α-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究.实用肝脏病杂志,2017,20(3):284-289.
[7]Turnes J,Romero-Gómez M,Planas R,et al.Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain.Gastroenterol Hepatol,2013,36(9):555-564.
[8]中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[9]Suh DJ,Lee HC,Byun KS,et al.Efficacy and safety of pegylated interferon-α2a in patients with lamivudine-resistant HBe Agpositive chronic hepatitis B.Antivir Ther,2013,18(6):765-773.
[10]Ning Q,Han M,Sun Y,et al.Switching from entecavir to Peg IFNalfa-2a in patients with HBe Ag-positive chronic hepatitis B:Arandomi sed open-label trial(OSST trial).J Hepatol,2014,61(4):777-784.
[11]Jie Y,Li X,Lin G,et al.Real-life practice of antiviral therapy and disease patterns of patients with chronic hepatitis B:a single-center retrospective observation study.Hepatol Int,2014,8(4):501-507.
[12]Wong GLH,Yiu KKL,Wong VWS,et al.Meta-analysis:reduction in hepatic events following interferon-alfa therapy of chronic hepatitis B.Aliment Pharmacol Ther,2010,32(9):1059-1068.
[13]贾妮娜,林兰意,郭斯敏,等.长效干扰素α-2a治疗慢性乙型肝炎过程中外周血浆样树突状细胞的变化及其与疗效的关系.中华肝脏病杂志,2015,23(1):34-39.
[14]封波,尚佳,武淑环,等.聚乙二醇干扰素α-2b(Y型,40k D)注射液治疗基因1/6型慢性丙型肝炎患者的疗效和安全性分析.中华肝脏病杂志,2017,25(3):187-194.
[15]Miyase S,Morishita Y,Haraoka K,et al.1142 Peg-IFNα-2a plus ribavirin shows higher SVR rate compare with pegIFNa-2b plus ribavirin in elder patients with chronic hepatitis C specially in IL-28B major allele.J Hepatol,2012,56(Suppl 2):S451-S451.
[16]Karabay O,Tuna N,Esen S,et al.Comparative efficacy of pegylated interferonsα-2a and 2b in the treatment of HBe Agnegative chronic hepatitis B infection.Eur J Gastroenterol Hepatol,2012,24(11):1296-1301.
[17]Dogan UB,Golge N,Akin MS.The comparison of the efficacy of pegylated interferonα-2a andα-2b in chronic hepatitis Bpatient].Eur J Gastroenterol Hepatol,2013,25(9):1312-1316.
[18]Thompson AJ,Colledge D,Rodgers S,et al.Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro.Antivir Ther,2009,14(6):797-808.
[19]Ferns RB,Naoumov NV,Gilson RJ,et al.Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBe Ag loss.J Clini Virol,2007,39(3):199-204.
[20]侯凤琴,尹亚琳,曾玲英,等.聚乙二醇干扰素α-2b(Y型,40k D)注射液治疗HBe Ag阳性慢性乙型肝炎患者的疗效和安全性分析.中华肝脏病杂志,2017,25(8)589-596.