成人乙肝病毒相关性膜性肾病免疫抑制治疗疗效回顾性分析
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摘要
目的:探讨成人乙肝病毒相关性膜性肾病(hepatitis B virus-associated membranous nephritis,HBV-MN)患者能否参考特发性膜性肾病(idiopathic membranous nephritis,IMN)给予免疫抑制治疗,以及联合抗病毒治疗在HBV-MN患者肝、肾保护方面的价值。方法:回顾性收集HBV-MN患者及IMN患者临床随访资料,对比两组患者在接受免疫抑制治疗后肾脏病缓解和肝损伤发生情况,并进一步对比联合抗病毒治疗HBV-MN患者与未抗病毒治疗HBV-MN患者肾脏病缓解和肝损伤发生情况。结果:在免疫抑制治疗方案相当的情况下,48周时,HBV-MN组与IMN组完全缓解率分别为60.7%及51.9%,两组差异无统计学意义(P>0.05),但HBV-MN组肝损伤发生率高于IMN组(P<0.001),分别为42.9%及7.7%;接受抗病毒治疗HBV-MN患者与未接受抗病毒治疗HBV-MN患者肾病完全缓解率分别为43.8%及83.3%,差异有统计学意义(P<0.001),而两组肝损伤发生率分别为18.8%与50.0%,差异无统计学意义(P>0.05)。结论:在综合考虑肝、肾获益的基础上,对于临床表现为肾病综合征的成人HBV-MN患者,可在抗病毒治疗的基础上,参照IMN的方案进行免疫抑制治疗。
Objective: To investigate whether adult patients with hepatitis B virus associated membranous nephropathy( HBV-MN) can receive immunosuppressive therapy imitating the regimens of idiopathic membranous nephritis( IMN) and the roles of combined therapy with nucleoside antiviral drugs on kidney and liver protection. Methods: Clinical follow-up data of patients with IMN and patients with HBV-MN having received immunosuppressive therapy were collected retrospectively. The rate of nephrotic syndrome remission and incidence of liver injury were compared between the patients with HBV-MN and the patients with IMN,as well as the HBV-MN patients with or without combining nucleoside antiviral therapy. Results: After receiving 48 weeks treatment of similar immunosuppressive regimens,complete remission rate of nephrotic syndrome was 60. 7% in HBV-MN group and 51. 9% in IMN group,which was not significantly different between the two groups. Incidence of liver injury was 42. 9% in HBV-MN group,which was much higher than 7. 7% of IMN group( P < 0. 001). Furthermore,among the patients with HBV-MN,complete remission rate of nephrotic syndrome was 43. 8% and 83. 3% respectively in HBV-MN patients with or without combined therapy with antiviral drugs( P < 0. 001),but the incidence of liver injury was not significantly different between the two groups( 18. 8% vs 50. 0%,P > 0. 05). Conclusion: When considering the benefit of liver and kidney,HBV-MN patients with nephritic-range proteinuria can be treated with immunosuppressive therapy imitating the regimens of IMN,and combination with nucleoside antiviral drugs to prevent immunosuppressant-induced hepatitis activation.
Objective: To investigate whether adult patients with hepatitis B virus associated membranous nephropathy( HBV-MN) can receive immunosuppressive therapy imitating the regimens of idiopathic membranous nephritis( IMN) and the roles of combined therapy with nucleoside antiviral drugs on kidney and liver protection. Methods: Clinical follow-up data of patients with IMN and patients with HBV-MN having received immunosuppressive therapy were collected retrospectively. The rate of nephrotic syndrome remission and incidence of liver injury were compared between the patients with HBV-MN and the patients with IMN,as well as the HBV-MN patients with or without combining nucleoside antiviral therapy. Results: After receiving 48 weeks treatment of similar immunosuppressive regimens,complete remission rate of nephrotic syndrome was 60. 7% in HBV-MN group and 51. 9% in IMN group,which was not significantly different between the two groups. Incidence of liver injury was 42. 9% in HBV-MN group,which was much higher than 7. 7% of IMN group( P < 0. 001). Furthermore,among the patients with HBV-MN,complete remission rate of nephrotic syndrome was 43. 8% and 83. 3% respectively in HBV-MN patients with or without combined therapy with antiviral drugs( P < 0. 001),but the incidence of liver injury was not significantly different between the two groups( 18. 8% vs 50. 0%,P > 0. 05). Conclusion: When considering the benefit of liver and kidney,HBV-MN patients with nephritic-range proteinuria can be treated with immunosuppressive therapy imitating the regimens of IMN,and combination with nucleoside antiviral drugs to prevent immunosuppressant-induced hepatitis activation.
引文
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12 .Chen Y,Schieppati A,Chen X,et al.Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.Cochrane Database Syst Rev,2014.
13 .刘威,刘昊虹,周兵,等.钙调神经磷酸酶抑制剂与环磷酰胺治疗特发性膜性肾病的疗效分析.中国中西医结合肾病杂志,2017,18(4):338-339.
14 .黄少珍,唐德燊,刘华锋.膜性肾病的治疗研究进展.广东医学院学报,2008,26:316-318.
15 .Lai FM,Tam JS,Li PK,et al.Replication of hepatitis B virus with corticosteroid therapy in hepatitis B virus related membranous nephropathy.Virchows Arch A Pathol Anat Histopathol,1989,414(3):279-284.
16 .Lai KN,Tam JS,Lin HJ,et al.The therapeutic dilemma of the usage of corticosteroid in patients with membranous nephropathy and persistent hepatitis B virus surface antigenanemia.Nephron,1990,54(1):12-17.
17 .Akimoto T,Otake T,Tanaka A,et al.Steroid treatment in patients with membranous nephropathy and hepatitis B virus surface antigenemia:a report of two cases.Clin Exp Nephrol,2011,15(2):289-293.
18 .Zheng XY,Wei RB,Tang L,et al.Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis.World J Gastroenterol,2012,18(8):821-832.
19 .Ochi A,Ishimura E,Ichii M,et al.Successful Treatment of Hepatitis B Virus-associated Membranous Nephropathy with Entecavir and Immunosuppressive Agents.Nephrology(Carlton),2014,19(9):595-596.
20 .孙玲,邹陆曦,陈茂杰.抗乙肝病毒联合免疫抑制治疗成人乙肝相关性肾炎Meta分析.中国中西医结合肾病杂志,2015,16(3):237-241.
21 .Tang S,Lai KN.Hepatitis B-related membranous nephropathy should be treated with a specific anti-viral agent.Kidney Int,2006,70(4):818.
22 .Das P,Vivek V,Ford M,et al.Hepatitis B virus related membranous glomerulonephritis and proteinuria treated with lamivudine and tenofovir.BMJ Case Reports,2011,31:2011.
23 .Yang YF,Xiong QF,Zhao W,et al.Complete remission of hepatitis B virus-related membranous nephropathy after entecavir monotherapy.Clin Res Hepatol Gastroenterol,2012,36(5):e89-e92.
24 .Xiong QF,Zhong YD,Hu ZL,et al.Successful treatment of occult hepatitis B virus infection related membranous nephropathy after entecavir therapy.Acta Clin Belg,2014,19(9):595-596.
25 .王淑君,姚翠微,陈锐鸿,等.合并HBV感染肾炎患者免疫抑制治疗的肝脏安全性.中华肾病研究电子杂志,2017,6(3):114-119.
2 .Zhang X,Liu S,Tang L,et al.Analysis of pathological data of renal biopsy at one single center in China from 1987 to 2012.Chin Med J,2014,127(9):1715-1720.
3 .魏日胞,李平,吴杰,等.205例乙型肝炎病毒相关性肾炎的临床及病理研究.中华实验和临床病毒学杂志,2010,24(6):464-467.
4 .Lai KN,Li PK,Lui SF,et al.Membranous nephropathy related to hepatitis B virus in adults.N Engl J Med,1991,324(21):1457-1463.
5 .Kleinknecht C,Levy M,Peix A,et al.Membranous glomerulonephritisand hepatitis B surface antigen in children.J Pediatrics,1979,95(6):946-952.
6 .Hofstra JM,Fervenza FC,Wetzels JF.Treatment of idiopathic membranous nephropathy.Nat Rev Nephrol,2013,9(8):443-458.
7 .田沂,龚国忠.乙型肝炎病毒再激活致肝衰竭病例及其机制分析.中华肝脏病杂志,2014,22(4):272-276.
8 .Kong D,Wu D,Wang T,et al.Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection.Int J Infect Dis,2013,17(7):e535-e538.
9 .Ehrenrich T,Churg J.Pathology of membranous nephropathy.In:Sommers SC(ed)pathology annual.Appleton-CenturyCrofts,New York,1968.145-186.
10 .Seetharam A,Perrillo R,Gish R.Immunosuppression in Patients with Chronic Hepatitis B.Curr Hepatol Rep,2014,13(3):235
11 .Schieppati A,Perna A,Zamora J,et al.Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.Cochrane Database Syst Rev,2004,18(4):CD004293.
12 .Chen Y,Schieppati A,Chen X,et al.Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.Cochrane Database Syst Rev,2014.
13 .刘威,刘昊虹,周兵,等.钙调神经磷酸酶抑制剂与环磷酰胺治疗特发性膜性肾病的疗效分析.中国中西医结合肾病杂志,2017,18(4):338-339.
14 .黄少珍,唐德燊,刘华锋.膜性肾病的治疗研究进展.广东医学院学报,2008,26:316-318.
15 .Lai FM,Tam JS,Li PK,et al.Replication of hepatitis B virus with corticosteroid therapy in hepatitis B virus related membranous nephropathy.Virchows Arch A Pathol Anat Histopathol,1989,414(3):279-284.
16 .Lai KN,Tam JS,Lin HJ,et al.The therapeutic dilemma of the usage of corticosteroid in patients with membranous nephropathy and persistent hepatitis B virus surface antigenanemia.Nephron,1990,54(1):12-17.
17 .Akimoto T,Otake T,Tanaka A,et al.Steroid treatment in patients with membranous nephropathy and hepatitis B virus surface antigenemia:a report of two cases.Clin Exp Nephrol,2011,15(2):289-293.
18 .Zheng XY,Wei RB,Tang L,et al.Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis.World J Gastroenterol,2012,18(8):821-832.
19 .Ochi A,Ishimura E,Ichii M,et al.Successful Treatment of Hepatitis B Virus-associated Membranous Nephropathy with Entecavir and Immunosuppressive Agents.Nephrology(Carlton),2014,19(9):595-596.
20 .孙玲,邹陆曦,陈茂杰.抗乙肝病毒联合免疫抑制治疗成人乙肝相关性肾炎Meta分析.中国中西医结合肾病杂志,2015,16(3):237-241.
21 .Tang S,Lai KN.Hepatitis B-related membranous nephropathy should be treated with a specific anti-viral agent.Kidney Int,2006,70(4):818.
22 .Das P,Vivek V,Ford M,et al.Hepatitis B virus related membranous glomerulonephritis and proteinuria treated with lamivudine and tenofovir.BMJ Case Reports,2011,31:2011.
23 .Yang YF,Xiong QF,Zhao W,et al.Complete remission of hepatitis B virus-related membranous nephropathy after entecavir monotherapy.Clin Res Hepatol Gastroenterol,2012,36(5):e89-e92.
24 .Xiong QF,Zhong YD,Hu ZL,et al.Successful treatment of occult hepatitis B virus infection related membranous nephropathy after entecavir therapy.Acta Clin Belg,2014,19(9):595-596.
25 .王淑君,姚翠微,陈锐鸿,等.合并HBV感染肾炎患者免疫抑制治疗的肝脏安全性.中华肾病研究电子杂志,2017,6(3):114-119.