题名

B型肝炎和新發糖尿病對腎移植患者的影響:台灣健保資料庫研究

并列篇名

The Impact of HBV and New Onset Diabetes in Renal Transplant Recipients:A Nationwide Cohort Study in Taiwan

作者

魏漢源

关键词

臺灣健保險資料庫之特殊重大傷病醫療資源使用族群(LHID-CIP) ; 移植術後的新發糖尿病 ; B型肝炎 ; 肝癌 ; 腎臟移植 ; Longitudinal Health Insurance Database for catastrophic illness patients(LHID-CIP) ; New-onset diabetes after transplantation(NODAT) ; hepatitis B virus(HBV) ; hepatocellular carcinoma(HCC) ; Kidney transplantation

期刊名称

中山醫學大學醫學研究所學位論文

卷期/出版年月

2017年

学位类别

碩士

导师

張浤榮

内容语文

繁體中文

中文摘要

研究目的: 本研究的目的是探討B型肝炎與移植後新發糖尿病之間的關聯,了解這些對腎移植受者的影響,並為醫療服務及預防醫學提供參考。 研究資料及方法: 使用臺灣健保險資料庫之特殊重大傷病醫療資源使用族群(LHID-CIP)建立世代研究。其中新發糖尿病(NODAT)定義為腎臟移植後之新診斷,慢性B型肝炎(HBV)則設定為移植前已有之感染狀態。藉由此二變量,將腎移植受者構建成四組:1)A組具有NODAT(-)/ HBV(-)2,341人的世代;2)B組具有NODAT(+)/ HBV(-)432人的世代;3)C組具有NODAT(-)/ HBV(+)204人的世代;4)D組具有NODAT(+)/ HBV(+)34人的世代。所有腎移植受者總共3,011人均自2000年開始追蹤,終點評估(end point)則以發生透析依賴(dialysis dependent)失償性肝硬化或肝癌(cirrhosis, decompensation, or hepatocellular carcinoma)、病患死亡(death)或直至2011年底為止,以先到者為準。 研究結果: 在各組當中以多變量Cox模型分析,C組具有相對略高的透析依賴性風險(aHR = 1.43, 95% CI = 1.01-2.03);肝損害風險分別在D組為8.77倍,B組為5.66倍,C組為2.17倍(95% CI = 2.71-28.4, 3.34-9.58 和1.21-3.89);而較高的死亡風險呈現在C組和B組(aHR = 1.90和1.96, 95% CI = 1.39-2.59和1.29-2.99)。 結論與建議: 腎臟移植術後的新發糖尿病為失償性肝功能惡化、肝硬化或肝癌之風險因素,而慢性B型肝炎明顯會加重此危害;除追蹤移植腎患者之腎臟功能外,定期肝臟檢查應當作為腎移植患者之定期評估。而盡量減少新發糖尿病之形成與B型肝炎之防治,也應該是預防的一部份,將有助於提升腎臟移植術後的長期存活率。

英文摘要

Objective: The objective of this study is to explore the connection between the hepatitis B carrier and new onset diabetes after kidney transplantation and to understand those influences on renal transplant recipients, designing and conduct with other dimensions to provide references for medical care. Materials and Methods: We conducted a nationwide cohort study by using Longitudinal Health Insurance Database for catastrophic illness patients(LHID-CIP). New-onset diabetes was defined by the diagnosis after kidney transplantation, and chronic hepatitis B was described as pre-transplantation infection status. Four cohorts were constructed from the renal transplant recipients by variables: 1)A cohort(n = 2,341), with NODAT(-)/ HBV(-); 2)B cohort(n = 432), with NODAT(+)/ HBV(-); 3)C cohort(n = 204), with NODAT(-)/ HBV(+); 4)D cohort(n = 34), with NODAT(+)/ HBV(+). All renal transplant recipients(n = 3,011)were followed up from the inception point of 2000 until the development of dialysis-dependent, cirrhosis, liver decompensation, hepatocellular carcinoma(HCC), withdrawal from insurance or December 2011. Results: Among the subgroups, the C cohort had a slightly higher risk with dialysis-dependent(aHR = 1.43, 95% CI = 1.01-2.03)compared to A cohort in multivariable Cox model. The risk of liver disease with cirrhosis, decompensation, or HCC respectively were 8.77-fold in D cohort, 5.66-fold in B cohort, and 2.17-fold in C cohort than A cohort(95% CI = 2.71-28.4, 3.34-9.58 and 1.21-3.89, separately). Contrast with A cohort, C and B cohorts had a significantly higher mortality risk(aHR = 1.90 and 1.96, 95% CI = 1.39-2.59 and 1.29-2.99, respectively). Conclusions: New-onset diabetic after renal transplantation is the risk factor for liver decompensation, cirrhosis or hepatocellular carcinoma. The chronic hepatitis B can exacerbate the above hazard risk. Regular liver examinations should be therefore considered on the renal transplant recipients. The approach to minimize the development of new-onset diabetes and the prevention of hepatitis B infection should be parts of the treatment and that will improve the long-term survival after renal transplantation.

主题分类 醫藥衛生 > 醫藥總論
醫學院 > 醫學研究所
参考文献
  1. 李幸玲(2005).以大愛布施-由《華嚴經》內財布施論「器 官捐贈」. 玄奘佛學研究 ,3,31–53。
    連結:
  2. 王家良, 楊得政, 王守玠, 張淑鈺. (2016). 換腎洗腎存活率比一比 Comparison of Survival between Patients of Renal Transplant and Hemodialysis. 腎臟與透析 Kidney and Dialysis, 28, 1–4. https://doi.org/10.6340/KD.2016.28(1).01
    連結:
  3. 吳泰德張志宗. (2016). 老年末期腎臟病與腎臟替代療法 Renal Replacement Therapy in Geriatric End Stage Renal Disease Patients. 腎臟與透析 Kidney and Dialysis, 28, 130–133. https://doi.org/10.6340/KD.2016.28(3).06
    連結:
  4. 林秋菊. (2016). 活體腎臟移植之推動 Promoting living kidney transplantation. 護理雜誌 The Journal of Nursing, 63, 33–38. https://doi.org/10.6224/JN.63.2.33
    連結:
  5. 陳致中, 游棟閔, 吳明儒, 徐國雄, 鄭志雄. (2016). B型肝炎與腎臟移植. 腎臟與透析 Kidney and Dialysis, 28, 22–26. https://doi.org/10.6340/KD.2016.28(1).06
    連結:
  6. 蔡秉諺. (2010). 台灣慢性腎臟疾病患者盛行率與醫療利用分析 - 以健保資料庫為例 Prevalence and Health Service Utilization of Chronic Kidney Disease in Taiwan - A Population-based Study.
    連結:
  7. Burroughs, T. E., Swindle, J., Takemoto, S., Lentine, K. L., Machnicki, G., Irish, W. D., Schnitzler, M. A. (2007). Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients. Transplantation, 83, 1027–34. https://doi.org/10.1097/01.tp.0000259617.21741.95
    連結:
  8. Chakkera, H. A., Weil, E. J., Swanson, C. M., Dueck, A. C., Heilman, R. L., Reddy, K. S., Knowler, W. C. (2011). Pretransplant risk score for new-onset diabetes after kidney transplantation. Diabetes Care, 34, 2141–2145. https://doi.org/10.2337/dc11-0752
    連結:
  9. Chen, Y. C., Su, Y. C., Li, C. Y., &Hung, S. K. (2015). 13-year nationwide cohort study of chronic kidney disease risk among treatment-naive patients with chronic hepatitis B in Taiwan. BMC Nephrol, 16, 110. https://doi.org/10.1186/s12882-015-0106-5
    連結:
  10. Chen, Y.-C., Su, Y.-C., Li, C.-Y., Wu, C.-P., &Lee, M.-S. (2015). A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan. Kidney International, 87, 1030–1038. https://doi.org/10.1038/ki.2014.363
    連結:
  11. Cole, E. H., Johnston, O., Rose, C. L., &Gill, J. S. (2008). Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clinical Journal of the American Society of Nephrology, 3, 814–821. https://doi.org/10.2215/CJN.04681107
    連結:
  12. Cosio, F. G., Kudva, Y., van derVelde, M., Larson, T. S., Textor, S. C., Griffin, M. D., &Stegall, M. D. (2005). New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney International, 67, 2415–21. https://doi.org/10.1111/j.1523-1755.2005.00349.x
    連結:
  13. Cosio, F. G., Pesavento, T. E., Kim, S., Osei, K., Henry, M., &Ferguson, R. M. (2002). Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney International, 62, 1440–6. https://doi.org/10.1111/j.1523-1755.2002.kid582.x
    連結:
  14. Duhart, B. T., Honaker, M. R., Shokouh-Amiri, M. H., Riely, C. A., Vera, S. R., Taylor, S. L., Gaber, A. O. (2003). Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation. Transplant Infectious Disease : An Official Journal of the Transplantation Society, 5, 126–31.
    連結:
  15. Fabrizi, F., Martin, P., Dixit, V., Kanwal, F., &Dulai, G. (2005). HBsAg seropositive status and survival after renal transplantation: Meta-analysis of observational studies. American Journal of Transplantation, 5, 2913–2921. https://doi.org/10.1111/j.1600-6143.2005.01113.x
    連結:
  16. Fu, S.-C., Huang, Y.-W., Wang, T.-C., Hu, J.-T., Chen, D.-S., &Yang, S.-S. (2015). Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with new onset diabetes: a nationwide cohort study. Alimentary Pharmacology & Therapeutics, 41, 1200–1209. https://doi.org/10.1111/apt.13191
    連結:
  17. Guillevin, L., Lhote, F., Cohen, P., Sauvaget, F., Jarrousse, B., Lortholary, O., Trépo, C. (1995). Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine, 74, 238–53.
    連結:
  18. Hjelmesaeth, J., Hartmann, A., Kofstad, J., Stenstr?m, J., Leivestad, T., Egeland, T., &Fauchald, P. (1997). Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation, 64, 979–83.
    連結:
  19. Huang, Y.-W., Wang, T.-C., Lin, S.-C., Chang, H.-Y., Chen, D.-S., Hu, J.-T., Kao, J.-H. (2013). Increased Risk of Cirrhosis and Its Decompensation in Chronic Hepatitis B Patients With Newly Diagnosed Diabetes: A Nationwide Cohort Study. Clinical Infectious Diseases, 57, 1695–1702. https://doi.org/10.1093/cid/cit603
    連結:
  20. Jindal, R. M., &Hjelmesaeth, J. (2000). Impact and management of posttransplant diabetes mellitus. Transplantation, 70(11 Suppl), SS58-63.
    連結:
  21. Johnson, R. J., &Couser, W. G. (1990). Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney International, 37, 663–76.
    連結:
  22. Kanaan, N., Kabamba, B., Mar?chal, C., Pirson, Y., Beguin, C., Goffin, E., &Hassoun, Z. (2012). Significant rate of hepatitis B reactivation following kidney transplantation in patients with resolved infection. Journal of Clinical Virology, 55, 233–238. https://doi.org/10.1016/j.jcv.2012.07.015
    連結:
  23. Kotton, C. N., &Fishman, J. A. (2005). Viral infection in the renal transplant recipient. Journal of the American Society of Nephrology : JASN, 16, 1758–74. https://doi.org/10.1681/ASN.2004121113
    連結:
  24. Kuo, H. T., Sampaio, M. S., Vincenti, F., &Bunnapradist, S. (2010). Associations of pretransplant diabetes mellitus, new-onset diabetes after transplant, and acute rejection with transplant outcomes: An analysis of the organ procurement and transplant network/united network for organ sharing (OPTN/UNOS) database. American Journal of Kidney Diseases, 56, 1127–1139. https://doi.org/10.1053/j.ajkd.2010.06.027
    連結:
  25. Lai, K. N., Ho, R. T., Tam, J. S., &Lai, F. M. (1996). Detection of hepatitis B virus DNA and RNA in kidneys of HBV related glomerulonephritis. Kidney International, 50, 1965–77.
    連結:
  26. Lee, J., Cho, J.-H., Lee, J. S., Ahn, D.-W., Kim, C.-D., Ahn, C., Lee, J. P. (2016). Pretransplant Hepatitis B Viral Infection Increases Risk of Death After Kidney Transplantation. Medicine, 95, e3671. https://doi.org/10.1097/MD.0000000000003671
    連結:
  27. Li, P., Wei, R.-B., Tang, L., Wu, J., Zhang, X.-G., &Chen, X.-M. (2012). Clinical and pathological analysis of hepatitis B virus-related membranous nephropathy and idiopathic membranous nephropathy. Clinical Nephrology, 78, 456–64.
    連結:
  28. Li, W. H., Chen, Y. J., Tseng, W. C., Lin, M. W., Chen, T. J., Chu, S. Y., Liu, H. N. (2012). Malignancies after renal transplantation in Taiwan: A nationwide population-based study. Nephrology Dialysis Transplantation, 27, 833–839. https://doi.org/10.1093/ndt/gfr277
    連結:
  29. Locatelli, F., Pozzoni, P., &Vecchio, L.del. (2004). Renal Replacement Therapy in Patients with Diabetes and End-Stage Renal Disease. Journal of the American Society of Nephrology, 15, S25–S29. https://doi.org/10.1097/01.ASN.0000093239.32602.04
    連結:
  30. Luan, F. L., Steffick, D. E., &Ojo, A. O. (2011). New-onset diabetes mellitus in kidney transplant recipients discharged on steroid-free immunosuppression. Transplantation, 91, 334–41. https://doi.org/10.1097/TP.0b013e318203c25f
    連結:
  31. Mohan, S., &Hirsch, J. (2013). Risk of Malignancy After Renal Transplantation. Transplantation Journal, 95, 17–18. https://doi.org/10.1097/TP.0b013e31827b3d70
    連結:
  32. Owda, A. K., Abdallah, A. H., Haleem, A., Hawas, F. A., Mousa, D., Fedail, H., Al-Khader, A. A. (1999). De novo diabetes mellitus in kidney allografts: Nodular sclerosis and diffuse glomerulosclerosis leading to graft failure. Nephrology Dialysis Transplantation, 14, 2004–2007. https://doi.org/10.1093/ndt/14.8.2004
    連結:
  33. Reddy, P. N., Sampaio, M. S., Kuo, H. T., Martin, P., &Bunnapradist, S. (2011). Impact of pre-existing hepatitis B infection on the outcomes of kidney transplant recipients in the united states. Clinical Journal of the American Society of Nephrology, 6, 1481–1487. https://doi.org/10.2215/CJN.09201010
    連結:
  34. Revanur, V. K., Jardine, A. G., Kingsmore, D. B., Jaques, B. C., Hamilton, D. H., &Jindal, R. M. (2001). Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clinical Transplantation, 15, 89–94.
    連結:
  35. Sarno, G., Muscogiuri, G., &DeRosa, P. (2012). New-Onset Diabetes After Kidney Transplantation. Transplantation Journal, 93, 1189–1195. https://doi.org/10.1097/TP.0b013e31824db97d
    連結:
  36. Schnitzler, M. (2003). Diabetes Mellitus After Kidney Transplantation in the United States. American Journal of Transplantation, 3, 1318–1318. https://doi.org/10.1046/j.1600-6143.2003.00228.x
    連結:
  37. Shah, T., Kasravi, A., Huang, E., Hayashi, R., Young, B., Cho, Y. W., &Bunnapradist, S. (2006). Risk factors for development of new-onset diabetes mellitus after kidney transplantation. Transplantation, 82, 1673–6. https://doi.org/10.1097/01.tp.0000250756.66348.9a
    連結:
  38. Wachs, M. E., Amend, W. J., Ascher, N. L., Bretan, P. N., Emond, J., Lake, J. R., Vincenti, F. (1995). The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors. Transplantation, 59, 230–4.
    連結:
  39. Wang, J. P., Kao, F. Y., Wu, C. Y., Hung, Y. P., Chao, Y., Chou, Y. J., &Li, C. P. (2015). Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients: A population-based cohort study. Cancer, 121, 1446–1455. https://doi.org/10.1002/cncr.29159
    連結:
  40. Wauters, R. P., Cosio, F. G., Suarez Fernandez, M. L., Kudva, Y., Shah, P., &Torres, V. E. (2012). Cardiovascular consequences of new-onset hyperglycemia after kidney transplantation. Transplantation, 94, 377–82. https://doi.org/10.1097/TP.0b013e3182584831
    連結:
  41. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, P. F. (1999). Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. The New England Journal of Medicine, 341, 1725–1730. https://doi.org/10.1056/NEJM199912023412303
    連結:
  42. Woodle, E. S., First, M. R., Pirsch, J., Shihab, F., Gaber, A. O., VanVeldhuisen, P., &Astellas Corticosteroid Withdrawal Study Group. (2008). A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Annals of Surgery, 248, 564–77. https://doi.org/10.1097/SLA.0b013e318187d1da
    連結:
  43. Yap, D. Y. H., Yung, S., Tang, C. S. O., Seto, W. K., Ma, M. K. M., Mok, M. M. Y., Chan, T. M. (2014). Entecavir treatment in kidney transplant recipients infected with hepatitis B. Clinical Transplantation, 28, 1010–1015. https://doi.org/10.1111/ctr.12410
    連結:
  44. Yap, D. Y. H., Tang, C. S. O., Yung, S., Choy, B. Y., Yuen, M. F., &Chan, T. M. (2010). Long-Term Outcome of Renal Transplant Recipients With Chronic Hepatitis B Infection—Impact of Antiviral Treatments. Transplantation, 90, 325–330. https://doi.org/10.1097/TP.0b013e3181e5b811
    連結:
  45. Lee, W. C., Wu, M. J., Cheng, C. H., Chen, C. H., Shu, K. H., &Lian, J. D. (2001). Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. American Journal of Kidney Diseases : The Official Journal of the National Kidney Foundation, 38, 1074–1081. http://doi.org/10.1053/ajkd.2001.28607
    連結:
  46. 參考文獻
  47. 中文部分
  48. 黃秋錦, 張智銘, 王舒民, 劉耀隆. (2010). 腎移植後B型肝炎的臨床處置. 腎臟與透析 Kidney and Dialysis, 22, 1–5.
  49. 2015 臺灣慢性腎臟病 臨床診療指引. (2015). 財團法人國家衛生研究院.
  50. 英文部分
  51. Hamed, A. E., Abas, B., Shaltout, I., Elsahar, M., Elweakil, R., Salih, S., Mogawer, S. (2015). Managing Diabetes and Liver Disease Association, Guidelines (Consensus) Development. Journal of Endocrinology, Diabetes & Obesity, 3.
  52. Hart, A., Smith, J. M., Skeans, M. A., Gustafson, S. K., Stewart, D. E., Cherikh, W. S., Israni, A. K. (2017). OPTN/SRTR 2015 Annual Data Report: Kidney. American Journal of Transplantation, 17, 21–116. https://doi.org/10.1111/ajt.14124
  53. John, S., Andersson, K. L., Kotton, C. N., Hertl, M., Markmann, J. F., Cosimi, A. B., &Chung, R. T. (2013). Prophylaxis of hepatitis B infection in solid organ transplant recipients. Therapeutic Advances in Gastroenterology, 6, 309–319. https://doi.org/10.1177/1756283X13487942
  54. Mathew, J. T., Rao, M., Job, V., Ratnaswamy, S., &Jacob, C. K. (2003). Post-transplant hyperglycaemia: a study of risk factors. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 18, 164–71.
  55. Mathurin, P., Mouquet, C., Poynard, T., Sylla, C., Benalia, H., Fretz, C., Bitker, M. O. (1999). Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology (Baltimore, Md.), 29, 257–263. https://doi.org/10.1002/hep.510290123
  56. Miles, A. M., Sumrani, N., Horowitz, R., Homel, P., Maursky, V., Markell, M. S., Friedman, E. A. (1998). Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation, 65, 380–4.
  57. Ojo, A. O., Leichtman, A. B., Punch, J. D., Hanson, J. A., Dickinson, D. M., Wolfe, R. A., Agodoa, L. Y. (2000). Impact of pre-existing donor hypertension and diabetes mellitus on cadaveric renal transplant outcomes. American Journal of Kidney Diseases : The Official Journal of the National Kidney Foundation, 36, 153–9. https://doi.org/10.1053/ajkd.2000.8288
  58. Schnuelle, P., Lorenz, D., Trede, M., &Van DerWoude, F. J. (1998). Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. Journal of the American Society of Nephrology : JASN, 9, 2135–41.
  59. Takekoshi, Y., Tochimaru, H., Nagata, Y., &Itami, N. (1991). Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney International. Supplement, 35, S34-9.
  60. Vesco, L., Busson, M., Bedrossian, J., Bitker, M. O., Hiesse, C., &Lang, P. (1996). Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors. Transplantation, 61, 1475–8.
  61. Lee, W., Shu, K., Cheng, C., &Wu, M. (2001). Long-Term Impact of Hepatitis B , C Virus, 23592525, 300–306.
  62. 2016 USRDS Annual Data Report, Volume 2: ESRD in the United States. (2016). United States Renal Data System. https://doi.org/10.1053/j.ajkd.2015.04.017