Experience of clinical treatment on patients on cirrhosis or liver cancer complicated with psoriasis after liver transplantation
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摘要:
目的 总结患有银屑病的肝移植受者免疫抑制治疗的临床经验。 方法 以5例肝硬化或肝细胞癌(肝癌)伴银屑病的肝移植受者为研究对象,其乙型肝炎病毒(HBV)血清标志物均阳性。术前采用诱导方案,术后早期采用他克莫司(FK506)+吗替麦考酚酯(MMF)+肾上腺皮质激素(激素)三联免疫抑制方案,1周内停用激素。3例乙型病毒性肝炎(乙肝)后肝硬化合并肝癌肝移植患者1个月内逐步转换为西罗莫司替代治疗;2例乙肝后肝硬化肝移植受者患者一直采用FK506加或不加MMF方案。全部患者均予抗HBV治疗。分析其基本情况、银屑病皮损面积和严重性指数(PASI)评分变化及术后免疫抑制剂治疗方案的调整情况。 结果 5例患者肝移植术后至投稿日随访(8.3±1.5)年,均存活。与术前相比,患者术后6个月PASI评分明显降低(P<0.05)。2例乙肝后肝硬化肝移植受者患者在术后2年后出现银屑病复发,PASI评分显著升高,改为西罗莫司替代FK506的治疗方案后逐步下降,术后3年开始维持在稳定状态,无进展;3例乙肝后肝硬化合并肝癌肝移植受者无复发。 结论 以西罗莫司为主的免疫抑制治疗方案可有效控制肝移植受者的银屑病病情,对HBV阳性患者应同时进行抗HBV治疗。 Abstract:Objective To summarize the clinical experience of immunosuppressive therapy for recipients suffering from psoriasis after liver transplantation. Methods Five patients diagnosed with cirrhosis or hepatocellular carcinoma(HCC) complicated with psoriasis after liver transplantation were recruited in this clinical trial. All participants were positive for serum biomarkers of hepatitis B virus (HBV). Induction therapy was adopted before surgery. Immunosuppressive regime of tacrolimus (FK506), mycophenolate mofetil (MMF) and adrenal cortical hormone (hormone)was implemented early after surgery. The hormone use was terminated within 1 week. Three cases of cirrhosis complicated with HCC due to chronic HBV infection were gradually switched to sirolimus substitution treatment within 1 month after liver transplantation. Two patients with cirrhosis were administered with FK506 with or without MMF following liver transplantation. All patients received anti-HBV therapy. Baseline data, changes in psoriasis area and severity index (PASI) score and adjustment of postoperative immunosuppressive agents were analyzed. Results Five patients undergoing transplantation were followed up until the submission date with a mean duration of (8.3±1.5) years and survived. Compared with preoperative values, PASI score was significantly reduced at postoperative 6 months (P<0.05). Two patients with cirrhosis had recurrent psoriasis at 2 years after liver transplantation. PASI score was significantly increased and steadily declined after sirolimus substitution therapy. These patients remained physically stable and did not progress at postoperative 3 years. Three patients suffering from cirrhosis complicated with HCC presented with no recurrence of psoriasis postoperatively. Conclusions Sirolimus-based immunosuppressive therapy can effectively control the progression of psoriasis in liver transplantation recipients. Anti-HBV treatment should be simultaneously implemented for HBV positive patients. -
Key words:
- Liver transplantation /
- Psoriasis /
- Sirolimus /
- Tacrolimus /
- Immunosuppressive agent /
- Severity index
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表 1 患有银屑病的肝移植受者的基本情况
Table 1. General conditions in recipients of liver transplantation with psoriasis
序 号 性 别 年 龄 原发病 手术 年份 PS病 史(年) MELD 评分 (分) AFP (μg/L) PASI 评分 (分) PS术后 缓解 (月) PS复发 (月) 术前方案 初始方案 维持方案 1 男 52 HCC、 CHB、 LC 2006 9 11.0 1 240 43 3.5 - Mel+OTC Ster+FK506+MMF Srl 2 男 51 CHB、 LC 2008 8 10.5 - 46 4.8 24 Mel+OTC Ster+ FK506+MMF FK506+MMF 3 女 49 HCC、 CHB、 LC 2008 10 12.0 1 000 40 3 - Mel+OTC Ster+ FK506+MMF Srl+MMF 4 女 55 CHB、 LC 2010 7.5 13.0 - 41 4.5 22 Mel+OTC Ster+ FK506+MMF FK506 5 男 48 HCC、 CHB、 LC 2009 6 16.0 1 240 39 2 - Mel+OTC Ster+ FK506+MMF Srl 注:HCC为肝细胞癌,CHB为慢性乙型肝炎,LC为肝硬化,PS为银屑病,MELD为终末期肝病模型,Mel为甲泼尼龙,Ster为激素,OTC为巴利昔单抗(舒莱),FK506为他克莫司,MMF为吗替麦考酚酯,Srl为西罗莫司,ALD为自身免疫性肝病,-为未复发或未检测到 -
[1] "Diani M, Altomare G, Reali E. T cell responses in psoriasis and psoriatic arthritis[J]. Autoimmun Rev, 2015, 14(4):286-292. doi: 10.1016/j.autrev.2014.11.012 [2] Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis[J]. Annu Rev Immunol, 2014,32: 227-255. doi: 10.1146/annurev-immunol-032713-120225 [3] Madankumar R, Teperman LW, Stein JA. Use of etanercept for psoriasis in a liver transplant recipient[J]. JAAD Case Rep, 2015,1(6):S36-S37. doi: 10.1016/j.jdcr.2015.09.012 [4] 中华医学会皮肤性病学分会银屑病学组. 中国银屑病治疗指南(2008版)[J]. 中国实用乡村医生杂志,2014,21(2):2-4.Psoriasis Study Group of Skin Venereal Diseases Branch of Chinese Medical Association. Guidelines of psoriasis treatment in China(2008)[J]. Chin Pract J Rural Doct,2014,21(2):2-4. [5] Kolios AG, Yawalkar N, Anliker M, et al. Swiss S1 guidelines on the systemic treatment of psoriasis vulgaris[J]. Dermatology,2016, 232(4):385-406. doi: 10.1159/000445681 [6] Yang ZS, Lin NN, Li L, et al. The Effect of TNF inhibitors on cardiovascular events in psoriasis and psoriatic arthritis: an updated Meta-analysis[J]. Clin Rev Allergy Immunol, 2016, 51(2):240-247. doi: 10.1007/s12016-016-8560-9 [7] Foroncewicz B, Mucha K, Lerut J, et al. Cyclosporine is superior to tacrolimus in liver transplant recipients with recurrent psoriasis[J]. Ann Transplant, 2014, 19: 427-433. doi: 10.12659/AOT.890754 [8] Reich K, Burden AD, Eaton JN, et al. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials[J]. Br J Dermatol,2012,166(1):179-188. doi: 10.1111/j.1365-2133.2011.10583.x [9] Collazo MH, González JR, Torres EA. Etanercept therapy for psoriasis in a patient with concomitant hepatitis C and liver transplant[J]. P R Health Sci J, 2008,27(4):346-347. http://cn.bing.com/academic/profile?id=1514365248&encoded=0&v=paper_preview&mkt=zh-cn [10] Hoover WD. Etanercept therapy for severe plaque psoriasis in a patient who underwent a liver transplant[J]. Cutis, 2007,80(3):211-214. http://cn.bing.com/academic/profile?id=2471107116&encoded=0&v=paper_preview&mkt=zh-cn [11] 夏念信,邱宝安,黄东东,等. 他克莫司治疗肝移植伴银屑病一例[J/CD].中华临床医师杂志(电子版),2013,7(4) : 1825-1826.Xia NX, Qiu BA, Huang DD, et al. Therapy of tacrolimus on liver transplantation with psoriasis for one case[J/CD]. Chin J Clin (Electr Edit),2013,7(4): 1825-1826. [12] Lythgoe M, Abraham S. Tacrolimus: an effective treatment in refractory psoriatic arthritis following biologic failure[J]. Clin Exp Rheumatol, 2016,34(1 Suppl 95):S12-S13. http://cn.bing.com/academic/profile?id=961857829&encoded=0&v=paper_preview&mkt=zh-cn [13] Wei KC, Lai PC. Combination of everolimus and tacrolimus: a potentially effective regimen for recalcitrant psoriasis[J]. Dermatol Ther,2015,28(1):25-27. doi: 10.1111/dth.2015.28.issue-1 [14] Tirado-Sánchez A, Ponce-Olivera RM. Preliminary study of the efficacy and tolerability of combination therapy with calcipotriene ointment 0.005% and tacrolimus ointment 0.1% in the treatment of stable plaque psoriasis[J]. Cutis,2012,90(3): 140-144. http://cn.bing.com/academic/profile?id=192649796&encoded=0&v=paper_preview&mkt=zh-cn [15] Laino L, DiCarlo A. Palmoplantar pustular psoriasis: clinical and video thermographic evaluation before and after topical tacrolimus treatment[J]. Arch Dermatol,2011,147(6): 760. doi: 10.1001/archdermatol.2011.120 [16] Foroncewicz B, Mucha K, Paczek L, et al. Anti-CD25 and tacrolimus therapy may not prevent early primary biliary cirrhosis recurrence after liver transplantation: two case reports[J]. Transplant Proc, 2003, 35(6): 2310-2312. doi: 10.1016/S0041-1345(03)00835-2 [17] Abu-Elmagd K, Van Thiel D, Jegasothy BV, et al. FK506: a new therapeutic agent for severe recalcitrant psoriasis[J]. Transplant Proc,1991,23(6):3322-3324. http://cn.bing.com/academic/profile?id=2007179975&encoded=0&v=paper_preview&mkt=zh-cn [18] Gilbert SC, Klintmalm G, Menter A, et al. Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. a word of caution in light of the expanding use of this ‘steroid-sparing’ agent[J]. Arch Intern Med, 1990,150(4):889-891. doi: 10.1001/archinte.1990.00390160129025 [19] Steglich RB, Meneghello LP, Carvalho AV, et al. The use of ustekinumab in a patient with severe psoriasis and positive HBV serology[J]. An Bras Dermatol, 2014,89(4):652-654. doi: 10.1590/abd1806-4841.20143013 [20] Cho YT, Chen CH, Chiu HY, et al. Use of anti-tumor necrosis factor-α therapy in hepatitis B virus carriers with psoriasis or psoriatic arthritis: a case series in Taiwan[J]. Dermatol, 2012,39(3):269-273. doi: 10.1111/j.1346-8138.2011.01434.x [21] Cassano N, Mastrandrea V, Principi M, et al. Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease[J]. J Biol Regul Homeost Agents, 2011,25(2):285-289. http://cn.bing.com/academic/profile?id=1415223797&encoded=0&v=paper_preview&mkt=zh-cn