Franco Sandra, Llibre Josep M, Jou Toni, Tural Cristina, Martínez Miguel Angel
IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.
Infectious Disease Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Heliyon. 2023 Jan 3;9(1):e12686. doi: 10.1016/j.heliyon.2022.e12686. eCollection 2023 Jan.
In a previous recent work, we recognized three plasma circulating microRNAs (miRNAs)-miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p-that correlate largely with liver fibrosis evolution in human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV) co-infected patients. Here, we investigated whether levels of these three circulating miRNAs can be associated to liver disease evolution in HIV-1/HCV co-infected patients which have achieved HCV sustained virologic response (SVR) 12 weeks after finishing treatment. Eighty-one chronic HIV-1/HCV co-infected patients were longitudinally recruited at baseline (T0) of DAA therapy and 12 weeks (T12) after finishing therapy. At T0 most of the study patients displayed transient elastography values linked to an advanced stage of liver fibrosis (F0-1 9%, F2 11%, F3 32%, F4 48%). Significant reductions in the levels of circulating miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p were detected at T12 in SVR patients, in the overall cohort ( < 0.0001, < 0.0001, and = 0.0008, respectively) and in patients with advanced (F3-4) liver fibrosis (p < 0.0001, p < 0.0001, and = 0.0011, respectively). Of note, no significant reduction in the study miRNA levels was found at T12 in patients who did not achieve SVR ( = 0.8750, = 0.1250, and = 0.1260, respectively). HCV-cured patients, in contrast to non-responders, significantly reduced their liver stiffness after two years of achieving SVR (p < 0.0001). DAA-induced SVR is linked with a significant reduction in circulating levels of miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p. Our results indicate that miRNA plasma levels may be a useful biomarker of liver damage progression in HIV-1/HCV co-infected individuals that reach DAA-induced SVR.
在之前的一项近期研究中，我们识别出三种血浆循环微小RNA（miRNA）——miR-100-5p_iso3p:-2、miR-122-5p和miR-192-5p，它们在很大程度上与1型人类免疫缺陷病毒（HIV-1）/丙型肝炎病毒（HCV）合并感染患者的肝纤维化进展相关。在此，我们研究了这三种循环miRNA的水平是否与完成治疗12周后实现HCV持续病毒学应答（SVR）的HIV-1/HCV合并感染患者的肝脏疾病进展相关。81例慢性HIV-1/HCV合并感染患者在直接抗病毒药物（DAA）治疗基线（T0）和完成治疗后12周（T12）进行纵向招募。在T0时，大多数研究患者的瞬时弹性成像值与肝纤维化晚期相关（F0-1为9%，F2为11%，F3为32%，F4为48%）。在T12时，SVR患者、总体队列（分别为<0.0001、<0.0001和=0.0008）以及肝纤维化晚期（F3-4）患者中，循环miR-100-5p_iso3p:-2、miR-122-5p和miR-192-5p的水平均显著降低（分别为p<0.0001、p<0.0001和=0.0011）。值得注意的是，未实现SVR的患者在T12时研究miRNA水平未发现显著降低（分别为=0.8750、=0.1250和=0.1260）。与无应答者相比，HCV治愈患者在实现SVR两年后肝脏硬度显著降低（p<0.0001）。DAA诱导的SVR与循环miR-100-5p_iso3p:-2、miR-122-5p和miR-192-5p水平的显著降低相关。我们的结果表明，miRNA血浆水平可能是达到DAA诱导SVR的HIV-1/HCV合并感染个体肝损伤进展的有用生物标志物。
