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中华实验和临床感染病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (06) : 507 -512. doi: 10.3877/cma.j.issn.1674-1358.2020.06.012

所属专题: 经典病例 文献

短篇论著

直接抗病毒药物治疗六例丙型肝炎病毒相关性皮肤损害患者的回顾性研究
赵蕴玉1, 贺彩妮1, 高培根1, 刘莹2, 姚雷清2, 高蓉2, 刘佳姝2, 魏伏3, 李慎4, 朱龙飞2, 李政霄2, 纪泛扑5,()   
  1. 1. 710004 西安市,西安交通大学第二附属医院感染科
    2. 710004 西安市,西安交通大学第二附属医院皮肤科
    3. 710004 西安市,西安交通大学第二附属医院感染科;710004 西安市,西安市第四医院重症医学科
    4. 710004 西安市,陕西省疾控中心病毒所
    5. 710004 西安市,西安交通大学第二附属医院感染科;710004 西安市,西安交通大学第二附属医院生物诊断与治疗国家地方联合工程中心;710004 西安市,陕西省肝脾疾病临床医学研究中心
  • 收稿日期:2020-09-27 出版日期:2020-12-25
  • 通信作者: 纪泛扑
  • 基金资助:
    陕西省自然科学基础研究计划资助(No. 2017JM8092); 中央高校基本科研业务费(No. Nxzy012019107); 西安交通大学医学部国家级后备人选菁英计划(No. 305)

A retrospective study of 6 patients with hepatitis C virus associated cutaneous manifestations treated with direct-acting antivirals

Yunyu Zhao1, Caini He1, Peigen Gao1, Ying Liu2, Leiqing Yao2, Rong Gao2, Jiashu Liu2, Fu Wei3, Shen Li4, Longfei Zhu2, Zhengxiao Li2, Fanpu Ji5,()   

  1. 1. Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
    2. Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
    3. Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China; Department of Critical Care Medicine, Xi’an Fourth Hospital, Xi’an 710004, China
    4. Institute of Virus, Shaanxi Province Center for Diseases Control and Prevention, Xi’an 710004, China
    5. Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China; National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China; Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi’an 710004, China
  • Received:2020-09-27 Published:2020-12-25
  • Corresponding author: Fanpu Ji
引用本文:

赵蕴玉, 贺彩妮, 高培根, 刘莹, 姚雷清, 高蓉, 刘佳姝, 魏伏, 李慎, 朱龙飞, 李政霄, 纪泛扑. 直接抗病毒药物治疗六例丙型肝炎病毒相关性皮肤损害患者的回顾性研究[J]. 中华实验和临床感染病杂志(电子版), 2020, 14(06): 507-512.

Yunyu Zhao, Caini He, Peigen Gao, Ying Liu, Leiqing Yao, Rong Gao, Jiashu Liu, Fu Wei, Shen Li, Longfei Zhu, Zhengxiao Li, Fanpu Ji. A retrospective study of 6 patients with hepatitis C virus associated cutaneous manifestations treated with direct-acting antivirals[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2020, 14(06): 507-512.

目的

探讨基于索磷布韦方案治疗丙型肝炎病毒(HCV)相关性皮肤损害的疗效和安全性。

方法

回顾性分析2016年2月至2019年9月西安交通大学第二附属医院收治的6例HCV相关性皮肤损害患者接受基于索磷布韦方案治疗的效果和安全性。评估其持续病毒学应答(SVR12)率,治疗过程和治疗结束后肝功能和皮损症状的变化以及安全性。

结果

6例患者年龄25~56岁;其中5例女性;2例肝硬化;3例基因型为HCV 1b,3例基因型为HCV 2a。皮损分别表现为阴囊湿疹、结节性痒疹、结节性红斑、扁平苔藓、干燥综合征和混和冷球蛋白血症相关皮损。2例患者病理确诊为HCV相关性皮损,4例患者临床诊断为HCV相关性皮损。患者接受索磷布韦/维帕他韦(3例)、索磷布韦/雷迪帕韦(2例)12周或索磷布韦/利巴韦林(1例)24周治疗。与基线水平相比,治疗结束或随访12周的丙氨酸氨基转移酶(ALT)显著降低、白蛋白(ALB)不变或升高,6例患者均获得SVR12且皮损均明显缓解。3例患者(阴囊湿疹、结节性痒疹、干燥综合征)皮损完全治愈,其他皮损包括结节性红斑、扁平苔藓、混和冷球蛋白血症相关皮损明显缓解,但需要接受免疫抑制剂和(或)细胞毒药物维持治疗。治疗期间未出现明显不良反应,随访期间皮损无复发。

结论

HCV可引起不同的肝外皮肤表现,基于索磷布韦的无干扰素方案治疗HCV相关皮肤损害有效且安全性良好。对于皮肤疾病经对症治疗后效果欠佳者,需要尽早行HCV筛查,确诊HCV感染后建议尽快给予抗病毒治疗。

Objective

To investigate the effect and tolerability of sofosbuvir-based regimens for hepatitis C virus (HCV) associated cutaneous manifestations.

Methods

The effect and tolerability of sofosbuvir-based direct-acting antivirals (DAAs) regimens for 6 patients with HCV infection and cutaneous manifestations in the Second Affiliated Hospital of Xi’an Jiaotong University were analyzed, retrospectively. The sustained virologic response at 12 weeks after end-of-treatment (SVR12), changes liver function, remission of skin lesions and safety during and after treatment were evaluated, respectively.

Results

The age of the 6 patients were 25-56 years old; including 5 female, 2 cases with cirrhosis, 3 cases with HCV genotype 1b and 3 cases with HCV genotype 2a. The cutaneous manifestations included eczema scrotum, prurigo nodosa, erythema nodosum, lichen planus, Sjogren’s syndrome and mixed cryoglobulinemia (MC)-associated rashes. Two patients were pathologically diagnosed as HCV-associated skin lesions, and 4 patients were clinically diagnosed. Patients received sofosbuvir/velpatasvir (3 cases) or sofosbuvir/ledipasvir (2 cases) for 12 weeks and sofosbuvir/ribavirin (1 case) for 24 weeks. There were significant reductions in serum alanine aminotransferase from baseline to the end-of-treatment and 12 weeks post-treatment, with slight increase or no change in serum albumin. All 6 patients achieved SVR12 and significant improvement of cutaneous manifestations. Three patients (eczema scrotum, prurigo nodosa and Sjogren’s syndrome) achieved completed remission of skin lesions, other skin lesions (erythema nodosum, lichen planus and MC-associated rashes) that significantly relieved, but required immunosuppressive and (or) cytotoxic to maintain therapy. No patient had experienced significant side-effects and recurrence of skin damage during the follow-up.

Conclusions

HCV could cause different extrahepatic skin manifestations, sofosbuvir-based regimens achieved high SVR12 rate, and alleviated the skin lesions. Screening for HCV should be performed in patients with cutaneous manifestations as soon as possible when the effect of symptomatic therapy was unsatisfactory.

表1 6例HCV相关性皮肤损害患者的基线资料
图1 DAA药物治疗过程中患者皮损的变化
图2 HCV相关性结节性红斑病理学改变
[1]
Ramos-Casals M, Zignego AL, Ferri C, et al. Evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus infection[J]. J Hepatol,2017,66(6):1282-1299.
[2]
Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies[J]. World J Gastroenterol,2014,20(24):7544-7554.
[3]
Cacoub P, Poynard T, Ghillani P, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. multidepartment virus C[J]. Arthritis Rheum,1999,42(10):2204-2212.
[4]
Gill K, Ghazinian H, Manch R, et al. Hepatitis C virus as a systemic disease:reaching beyond the liver[J]. Hepatol Int,2016,10(3):415-423.
[5]
Cacoub P, Bourliere M, Lubbe J, et al. Dermatological side effects of hepatitis C and its treatment: Patient management in the era of direct-acting antivirals[J]. J Hepatol,2012,56(2):455-463.
[6]
Li ZX, Zhang YF, An JG, et al. Predictive factors for adverse dermatological events during pegylated/interferon alpha and ribavirin treatment for hepatitis C[J]. J Clin Virol,2014,60(3):190-195.
[7]
Ansarl U, Henderson LI, Stott G, et al. Treatment with ledipasvir-sofosbuvir for hepatitis C resulting in improvement of lichen planus[J]. JAAD Case Rep,2017,3(1):67-69.
[8]
Enomoto M, Tateishi C, Tsuruta D, et al. Remission of psoriasis after treatment of chronic hepatitis C virus infection with direct-acting antivirals[J]. Ann Intern Med,2018,168(9):678-680.
[9]
Nihei T, Kiniwa Y, Mikoshiba Y, et al. Improvement of porphyria cutanea tarda following treatment of hepatitis C virus by direct-acting antivirals: A case report[J]. J Dermatol,2019,46(5):149-151.
[10]
Degasperi E, Aghemo A, Colombo M. Treatment of extrahepatic manifestations of hepatitis C virus[J]. Clin Liver Dis,2017,21(3):631-643.
[11]
Polo ML, Laufer N. Extrahepatic manifestations of HCV: the role of direct acting antivirals[J]. Expert Rev Anti Infect Ther,2017,15(8):737-746.
[12]
中华医学会肝病学分会,中华医学会感染病学分会.丙型肝炎防治指南(2019年版)[J]. 中华肝脏病杂志,2019,27(12):962-979.
[13]
Satapathy SK, Bernstein D. Dermatologic disorders and the liver [J]. Clin Liver Dis,2011,15(1):165-182.
[14]
王文俊,杨颖,党双锁. HCV肝外表现研究现状[J]. 肝脏,2018,23(1):6-8.
[15]
金蕾,李晶晶.《多学科专家声明: HCV相关性肝外表现患者诊断指南》摘译[J]. 临床肝胆病杂志,2016,32(12):2263-2267.
[16]
Hatch MM, Nawas Z, Kollipara R, et al. Can curative antivirals benefit porphyria cutanea tarda in hepatitis C patients?[J]. J Eur Acad Dermatol Venereol,2017,31(4):194-194.
[17]
Saadoun D, Thibault V, Si Ahmed SN, et al. Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVAL-DIC study[J]. Ann Rheum Dis,2016,75(10):1777-1782.
[18]
Cacciola I, Borgia F, Filomia R, et al. Outcome of cutaneous psoriasis in hepatitis C virus-infected patients treated with direct-acting antiviral therapy[J]. J Viral Hepat,2020,27(3):333-337.
[19]
贺彩妮,李彧,葛蘅, 等. 基于索磷布韦方案治疗HCV相关性肾小球肾炎的效果和安全性[J]. 临床肝胆病杂志,2019,35(8):1714-1718.
[20]
Younossi ZM, Henry L, Ong PJ, et al. Systematic review with meta-analysis: extrahepatic manifestations in chronic hepatitis C virus-infected patients in East Asia[J]. Aliment Pharmacol Ther,2019,49(6):644-653.
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