低复制期慢乙肝药物治疗现状及中医药治疗前景
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摘要
从目前国内外药物治疗慢性乙型肝炎(以下简称慢乙肝)的现状出发,指出低复制期慢乙肝患者的药物治疗存在乙肝表面抗原(HBsAg)清除率低、安全停药难、应答率低、药物不良反应较多等不足。中药复方具有较好的抗HBV作用,在提高免疫力、综合改善临床症状方面具有显著效果。今后当着眼于慢乙肝低复制期中医病因病机、证候分型、体质的研究及其辨证组方与现代中药药理相结合的研究,以期为低复制期慢乙肝患者寻找到降低血清HBsAg滴度,提高HBsAg阴转率,减少患者因高水平HBsAg所带来疾病进展风险的中医药治疗新途径。
In the aspect of research status of western medicine therapy for chronic hepatitis B at low replication stage,this article pointed out that there exist certain disadvantages of low clearance rate for hepatitis B surface antigen,being difficult in drug suspension,high incidence of adverse reaction,etc. Chinese medicine compound formulas exert satisfactory anti-hepatitis B virus actions, and have certain effects on increasing immunity and relieving clinical symptoms. It is indicated that the future research should be focused on the study of etiology and pathogenesis,syndrome patterns and constitution distribution of chronic hepatitis B at low replication stage in the field of traditional Chinese medicine,and the methods of syndrome-differentiation prescription combined modern pharmacological study,thus to find out a approach to decrease hepatitis B surface antigen titer,increase the rate for hepatitis B surface antigen turning negative,and reduce the risk of deterioration of chronic hepatitis B induced by high hepatitis B surface antigen level.
In the aspect of research status of western medicine therapy for chronic hepatitis B at low replication stage,this article pointed out that there exist certain disadvantages of low clearance rate for hepatitis B surface antigen,being difficult in drug suspension,high incidence of adverse reaction,etc. Chinese medicine compound formulas exert satisfactory anti-hepatitis B virus actions, and have certain effects on increasing immunity and relieving clinical symptoms. It is indicated that the future research should be focused on the study of etiology and pathogenesis,syndrome patterns and constitution distribution of chronic hepatitis B at low replication stage in the field of traditional Chinese medicine,and the methods of syndrome-differentiation prescription combined modern pharmacological study,thus to find out a approach to decrease hepatitis B surface antigen titer,increase the rate for hepatitis B surface antigen turning negative,and reduce the risk of deterioration of chronic hepatitis B induced by high hepatitis B surface antigen level.
引文
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[18]Huang G,Yang Y,Shen F,et al.Early viral suppression predicts good postoperative survivals in patients with hepatocellular carcinoma with a high baseline HBV-DNA load[J].Ann Surg Oncol,2013,20(5):1482.
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[20]Chen C H,Lu S N,Hung C H,et al.The role of hepatitis Bsurface antigen quantification in predicting HBsAg loss and HBVrelapse after discontinuation of lamivudine treatment[J].JHepatol,2014,61(3):515.
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[22]Moucar I R,Boyer N,Ripault M P,et al.Sequential therapy with adefovir dipivoxil and pegylated interferon alfa-2a for HBeAg-negative patients[J].J Viral Hepat,2011,18(8):580.
[23]Kittner J M,Sprinzl M F,Grambihler A,et al.Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B[J].J Clin Virol,2012,54(1):93.
[24]Ning Q,Han M,Sun Y,et al.Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B:a randomised open-label trial(OSST trial)[J].JHepatol,2014,61(4):777.
[25]鲁艳平,周大桥,熊益群,等.凉血滋肾益气法对慢性乙肝患者树突状细胞和HBV-DNA的影响[J].中国实验方剂学杂志,2015,21(13):160.
[26]张传涛,扈晓宇,周道杰,等.基于“肾虚伏邪”理论论治HBeAg阳性慢性无症状乙型肝炎病毒携带者的临床观察[J].中国实验方剂学杂志,2014,20(3):175.
[27]贺劲松,周大桥,童光东,等.补肾健脾胶囊治疗慢性乙肝病毒携带者的随机双盲实验[J].中国实验方剂学杂志,2010,16(6):246.
[28]邵发助,江新荣.中西医结合治疗无症状乙肝病毒表面抗原携带者30例临床观察[J].实用中西医结合临床,2015(12):27.
[2]Feng-Min L U,Zhuang H.Management of hepatitis B in China[J].Chin Med J(Engl),2009,122(1):3.
[3]European Association for the Study of the Liver.EASL 2017Clinical Practice Guidelines on the management of hepatitis Bvirus infection[J].J Hepat,2017,67(2):370.
[4]Liaw Y F,Kao J H,Piratvisuth T,et al.Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2012update[J].Hepatol Int,2008,2(3):263.
[5]Terrault N A,Bzowej N H,Chang K M,et al.AASLDguidelines for treatment of chronic hepatitis B[J].Hepatology,2016,63(1):261.
[6]王贵强,王福生,成军,等.慢性乙型肝炎防治指南(2015年版)[J].中华实验和临床感染病杂志:电子版,2015,19(5):1.
[7]Dienstag J.Benefits and risks of nucleoside analog therapy for hepatitis B[J].Hepatology,2009,49(S5):S112.
[8]李海军,康富标,杨新英,等.干扰素及其治疗慢性乙型肝炎的研究进展[J].国际流行病学传染病学杂志,2010,37(2):133.
[9]WHO.Guidelines for the prevention,care and treatment of persons with chronic hepatitis B infection[EB/OL].http://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/.
[10]王晶晶,陈国凤,廖家杰.慢性乙型病毒性肝炎治疗现状和展望[J].传染病信息,2017,30(2):65.
[11]Chan H L,Wong V W,Wong G L,et al.A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B[J].Hepatology,2010,52(4):1232.
[12]Marcellin P,Heathcote E J,Buti M,et al.Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B[J].NEngl J Med,2008,359(23):2442.
[13]Gish R G,Lok A S,Chang T T,et al.Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B[J].Gastroenterology,2007,133(5):1437.
[14]Marcellin P,Lau G K,Bonino F,et al.Peginterferon alfa-2a alone,lamivudine alone,and the two in combination in patients with HBeAg-negative chronic hepatitis B[J].N Engl J Med,2004,351(12):1206.
[15]Marcellin P,Bonino F,Lau G K,et al.Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with Peg-interferon alpha-2a[J].Gastroenterology,2009,136(7):2169.
[16]Tseng T C,Liu C J,Su T H,et al.Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters[J].Gastroenterology,2011,141(2):517.
[17]Tseng T C,Liu C J,Yang H C,et al.High levels of hepatitis Bsurface antigen increase risk of hepatocellular carcinoma in patients with low HBV load[J].Gastroenterology,2012,142(5):1140.
[18]Huang G,Yang Y,Shen F,et al.Early viral suppression predicts good postoperative survivals in patients with hepatocellular carcinoma with a high baseline HBV-DNA load[J].Ann Surg Oncol,2013,20(5):1482.
[19]Liu W R,Tian M X,Jin L,et al.High levels of hepatitis B surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis B viral loads[J].Ann Surg Oncol,2015,22(3):843.
[20]Chen C H,Lu S N,Hung C H,et al.The role of hepatitis Bsurface antigen quantification in predicting HBsAg loss and HBVrelapse after discontinuation of lamivudine treatment[J].JHepatol,2014,61(3):515.
[21]Chen C H,Hung C H,Hu T H,et al.Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic hepatitis B virus infection[J].Clin Gastroenterol Hepatol,2015,13(11):1984.
[22]Moucar I R,Boyer N,Ripault M P,et al.Sequential therapy with adefovir dipivoxil and pegylated interferon alfa-2a for HBeAg-negative patients[J].J Viral Hepat,2011,18(8):580.
[23]Kittner J M,Sprinzl M F,Grambihler A,et al.Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B[J].J Clin Virol,2012,54(1):93.
[24]Ning Q,Han M,Sun Y,et al.Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B:a randomised open-label trial(OSST trial)[J].JHepatol,2014,61(4):777.
[25]鲁艳平,周大桥,熊益群,等.凉血滋肾益气法对慢性乙肝患者树突状细胞和HBV-DNA的影响[J].中国实验方剂学杂志,2015,21(13):160.
[26]张传涛,扈晓宇,周道杰,等.基于“肾虚伏邪”理论论治HBeAg阳性慢性无症状乙型肝炎病毒携带者的临床观察[J].中国实验方剂学杂志,2014,20(3):175.
[27]贺劲松,周大桥,童光东,等.补肾健脾胶囊治疗慢性乙肝病毒携带者的随机双盲实验[J].中国实验方剂学杂志,2010,16(6):246.
[28]邵发助,江新荣.中西医结合治疗无症状乙肝病毒表面抗原携带者30例临床观察[J].实用中西医结合临床,2015(12):27.