平均血小板体积对自身免疫性肝炎患者治疗不应答的预测价值分析

doi:10.3969/j.issn.1672-5069.2021.03.017

摘要/Abstract

摘要： 目的探讨自身免疫性肝炎(AIH)患者接受免疫抑制剂治疗不应答的影响因素。方法 2015年1月～2018年10月我院收治的 AIH 患者68例,接受标准的泼尼松或联合硫唑嘌呤治疗2年。使用血细胞分析仪检测血小板(PLT),自动给出平均血小板体积(MPV),所有患者接受肝活检。采用单因素和多因素Logistic回归分析影响AIH患者治疗不完全应答的预测因素。结果在治疗2年结束时,在68例AIH患者中实现完全应答42例(61.8%);入院时,完全应答患者MPV、γ-球蛋白、白蛋白(ALB)、TBIL、凝血酶原时间国际标准化比值(INR)和肌酐(Cr)分别为(8.5±2.0)fL、(23.8±5.2)%、(40.0±1.3)g/L、(23.4±3.9)μmol/L、(1.0±0.3)和(80.6±10.3)μmol/L,与不应答患者【分别为(10.3±2.3)fL、(33.1±7.1)%、(30.1±0.9)g/L、(36.2±5.3)μmol/L、(1.4±0.7)和(135.0±12.5)μmol/L】比,差异具有统计学意义(P<0.05),完全应答患者有肝硬化的比率为11.9%,显著低于不应答组的54.2%(P<0.05);以AIH患者治疗后应答与否为应变量,赋值0=完全应答,1=不应答,建立多因素 Logistic回归分析模型,将上表有统计学意义的因素如MPV、γ-球蛋白、ALB、TBIL、INR、Cr和肝硬化纳入Logistic回归模型分析,结果显示血清γ-球蛋白和白蛋白水平、MPV和是否存在肝硬化是AIH患者治疗不应答的独立预测因素(P<0.05)。结论 AIH患者可能对免疫抑制剂治疗不应答,MPV增大、高γ-球蛋白血症、低蛋白血症或存在肝硬化均是AIH患者治疗不应答的独立影响因素,针对这些难治性AIH患者需要进一步研究,以期制定出最佳的治疗策略。

关键词: 自身免疫性肝炎, 泼尼松, 硫唑嘌呤, 平均血小板体积, 治疗, 应答

Abstract: Objective This study aimed to investigate the impacting factors in response to immunosuppressive therapy in patients with autoimmune hepatitis (AIH).Methods A total of 68 patients with AIH were enrolled in our hospital between January 2015 and October 2018, including 18 males and 50 females, with an average age of (52.8±11.1) years old. All patients with AIH received standardized prednisone and azathioprine therapy for 24 months. All patients underwent twice liver biopsies before and after treatment, and blood mean platelet volume (MPV) and serum globulin level were detected. The univariate and multivariate Logistic regression analysis were applied to analyze the predictive factors that impact the poor response of patients with AIH to immunosuppressive treatment.Results At the end of two year treatment, 42(61.8%)out of the 68 patients with AIH in our series obtained complete response (CR) to immunosuppressive therapy; at presentation, the MPV, serum γ-globulin, albumin (ALB), total serum bilirubin, prothrombin time international normalized ratio (INR) and serum creatinine(sCr) levels were (8.5±2.0)fL, (23.8±5.2)%, (40.0±1.3)g/L, (23.4±3.9)μmol/L, (1.0±0.3) and (80.6±10.3)μmol/L, all significantly different compared to [(10.3±2.3)fL,(33.1±7.1)%, (30.1±0.9)g/L, (36.2±5.3)μmol/L, (1.4±0.7) and (135.0±12.5)μmol/L, respectively, P<0.05], the percentage of liver cirrhosis in patients with CR was 11.9%, much lower than 54.2%(P<0.05) in nonresponders; We took the response of patients with AIH after treatment as dependent variable, assigning 0=CR, 1=poor response, establishing a multivariate Logistic regression analysis model, and included the above-mentioned statistically significant factors such as MPV, γ-globulin, albumin, bilirubin, INR, sCr and liver cirrhosis into the Logistic regression model. The Logistic regression analysis showed that serum γ-globulin, albumin, MPV and liver cirrhosis were the independent predictors of poor response to immunosuppressive therapy in patients with AIH (P<0.05).Conclusion The patients with AIH might failed to immunosuppressive therapy, and elevated MPV, high γ-globulinemia and low serum albumin levels or even liver cirrhosis are the independent predictors of poor response. Further clinical trials are needed for these patients in order to get a best treatment strategy.

Key words: Autoimmune hepatitis, Prednisone, Azathioprine, Mean platelet volume, Therapy, Response

齐玫, 张瑞金, 田树萍, 于艳华. 平均血小板体积对自身免疫性肝炎患者治疗不应答的预测价值分析[J]. 实用肝脏病杂志, 2021, 24(3): 371-374.

Qi Mei, Zhang Ruijin, Tian Shuping, et al. Impacting factors in response to immunosuppressive therapy in patients with autoimmune hepatitis[J]. Journal of Practical Hepatology, 2021, 24(3): 371-374.

参考文献

[1] Zachou K, Muratori P, Koukoulis GK, et al. Autoimmune hepatitis-current management and challenges. Aliment Pharmacol Ther, 2013, 38:887-913.
[2]Gleeson D, Heneghan MA. British Society of Gastroenterology. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut, 2011, 60:1611-1629.
[3] Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology, 2010, 139:58-72,e74.
[4] Lee YM, Teo EK, Ng TM, et al. Autoimmune hepatitis in Singapore: a rare syndrome affecting middle-aged women. J Gastroenterol Hepatol, 2001, 16:1384-1389.
[5] Ngu JH, Bechly K, Chapman BA, et al.Population-based epidemiology study of autoimmune hepatitis: a disease of older women? J Gastroenterol Hepatol, 2010, 25:1681-1686.
[6] Werner M, Prytz H, Ohlsson B, et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol, 2008, 43:1232-1240.
[7] Lamers MM, van Oijen MG, Pronk M, et al. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol, 2010, 53:191-198.
[8] Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children: what is different from adult AIH? Semin Liver Dis, 2009, 29:297-306.
[9] Krawitt EL. Autoimmune hepatitis. N Engl J Med, 2006, 354:54-66.
[10] Verma S, Gunuwan B, Mendler M, et al. Factors predicting relapse and poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy. Am J Gastroenterol, 2004, 99:1510-1516.
[11] 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 自身免疫性肝炎诊断和治疗共识(2015 年).中华肝脏病杂志, 2016, 24(1):23-25.
[12] 张洪文, 刘会敏, 林睿,等. 自身免疫性肝炎治疗应答不良患者的临床特点分析. 中华肝脏病杂志, 2017, 25(10):755-759.
[13] Bnunt EM. Grading and staging the histopathological lesions of chronic hepatitis:the Knodell histology activity index and beyond. Hepatology, 2000, 3l(1): 241-246.
[14] Abe M, Mashiba T, Zeniya M, et al. Present status of autoimmune hepatitis in Japan: a nationwide survey. J Gastroenterol, 2011, 46(9):1136-1141.
[15] Kapila N,Higa JT,Longhi MS,et al. Autoimmune hepatitis: Clinical review with insights into the purinergic mechanism of disease. J Clin Transl Hepatol, 2013, 1(2):79-86.
[16] Gasparyan AY, Ayvazyan L, Mikhailidis DP, et al. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des, 2011, 17:47-58.
[17] Persico M, Niglio A, Valentini G, et al. Thrombocytopenia as a sensitive marker of immunologic activity in a patient with autoimmune chronic active hepatitis. Ital J Gastroenterol, 1996, 28:40-42.
[18] Muratori P, Lalanne C, Bianchi G, et al. Predictive factors of poor response to therapy in autoimmune hepatitis. Dig Liver Dis, 2016, 48:1078-1081.
[19] Ngu JH, Gearry RB, Frampton CM, et al. Predictors of poor outcome in patients with autoimmune hepatitis: a populationbased study. Hepatology, 2013, 57:2399-2406.
[20] Feld JJ, Dinh H, Arenovich T, et al. Autoimmune hepatitis: effect of symptomsand cirrhosis on natural history and outcome. Hepatology, 2005, 42:53-62.
[21] Yoshizawa K, Matsumoto A, Ichijo T, et al. Long-term outcome of Japanese patients with type 1 autoimmune hepatitis. Hepatology, 2012, 56:668-676.
[22] Czaja AJ, Carpenter HA.Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. Hepatology, 2006, 43:532-538.