Braz Aline Márcia Marques, Winckler Fernanda Cristina, Binelli Larissa Sarri, Chimeno Luis Guilherme, Lopes Lia Beatriz Mantovani, Lima Rodrigo Santos, Simões Rafael Plana, Grotto Rejane Maria Tommasini, Golim Marjorie de Assis, Silva Giovanni Faria
Graduate Program in Pathophysiology in Clinical Medicine, Department of Clinical Medicine, São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil.
Flow Cytometry Laboratory, Applied Biotechnology Laboratory - LBA, Clinical Hospital of Botucatu Medical School, Av. Prof. Mário Rubens Guimarães Montenegro, s/n, Botucatu, São Paulo, Brazil.
Clin Exp Med. 2021 Nov;21(4):587-597. doi: 10.1007/s10238-021-00708-w. Epub 2021 Apr 9.
Cirrhotic patients with chronic hepatitis C should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma even after sustained virological response (SVR). The stage of inflammatory resolution and regression of fibrosis is likely to happen, once treatment and viral clearance are achieved. However, liver examinations by elastography show that 30-40% of patients do not exhibit a reduction of liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C and characterize possible serum biomarkers with prognostic value. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines/chemokines and metalloproteinase inhibitors in the pretreatment (M1) and in the evaluation of SVR (M2). After exclusion criteria application, 16 patients included were once more evaluated in M3 (like M1) and classified into regressors (R) or non-regressors (NR), decrease or not ≥ 25% stiffness, respectively. The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that TCD4 + lymphocytes (absolute) are the most important biomarkers for the prediction of the regression (AUC = 0.90). NR patients presented levels less than R of liver stiffness since baseline, whereas NK cells were increased in NR. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in R and NR, thus allowing the development of a predictive model of regression of liver stiffness after SVR. These findings should be validated in greater numbers of patients.
即使获得持续病毒学应答（SVR），慢性丙型肝炎肝硬化患者仍应接受肝功能评估和肝细胞癌筛查监测。一旦实现治疗和病毒清除，炎症消退和纤维化逆转阶段可能会发生。然而，弹性成像肝脏检查显示，30%-40%的患者肝脏硬度未降低。这项研究是一项针对肝硬化患者的队列研究，目的是确定慢性丙型肝炎患者肝脏硬度逆转中涉及的免疫因素，并鉴定具有预后价值的血清生物标志物。样本总体包括31例肝硬化患者，他们在治疗前（M1）和SVR评估时（M2）接受了白细胞免疫表型分析、细胞因子/趋化因子和金属蛋白酶抑制剂定量检测。应用排除标准后，16例纳入患者在M3时再次接受评估（类似M1），并分别分为硬度降低≥25%的硬度逆转者（R）和未降低者（NR）。ROC曲线、机器学习（ML）和线性判别分析结果显示，TCD4+淋巴细胞（绝对值）是预测硬度逆转的最重要生物标志物（AUC=0.90）。自基线起，NR患者的肝脏硬度水平低于R组，而NR组NK细胞增加。因此，得出结论，R组和NR组循环免疫细胞谱存在差异，从而可以建立SVR后肝脏硬度逆转的预测模型。这些发现应在更多患者中进行验证。
