Busca C, Arias P, Sánchez-Conde M, Rico M, Montejano R, Martín-Carbonero L, Valencia E, Moreno V, Bernardino J I, Olveira A, Abadía M, González-García J, Montes M L
Unidad VIH, Servicio Medicina Interna, IdiPAz, Hospital Universitario La Paz, Madrid, Spain.
Instituto de Genética Médica y Molecular (INGEMM), IdiPaz, Hospital Universitario La Paz, Madrid, Spain.
Front Pharmacol. 2022 Aug 30;13:905126. doi: 10.3389/fphar.2022.905126. eCollection 2022.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. , , and have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between , , and and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (), rs58542926 (), and rs641738 (). The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the G allele variant [57.6% vs. 16.7% ( = 0.09)], but not or variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the G allele variant [69.4% vs. 39.1% ( < 0.05)] and the A allele variant [75% vs. 42% ( < 0.05)]. In our cohort, the gene variant was not associated with steatosis or steatohepatitis. The G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. The G allele variant and A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for and in PLWHIV with NAFLD to identify those at higher risk of progression.
非酒精性脂肪性肝病（NAFLD）是人类免疫缺陷病毒感染者（PLWHIV）肝脏损伤的常见原因。多项研究调查了NAFLD和脂肪性肝炎易感性的候选基因。据报道，[此处原文缺失具体基因名称]与丙氨酸转氨酶（ALT）水平升高、非酒精性脂肪性肝炎的组织学参数以及纤维化严重程度相关。我们的目的是分析[此处原文缺失具体基因名称]与PLWHIV合并NAFLD患者的脂肪变性、脂肪性肝炎和肝纤维化之间的关系。在西班牙的两个大型中心，对一组PLWHIV患者进行了评估，这些患者的转氨酶水平持续升高且疑似患有NAFLD，他们接受了肝活检并测定了基因变异。纳入本研究的所有参与者均进行了rs738409（[此处原文缺失具体基因名称]）、rs58542926（[此处原文缺失具体基因名称]）和rs641738（[此处原文缺失具体基因名称]）的基因分型。研究人群包括接受稳定抗逆转录病毒治疗的PLWHIV[7.7%为女性；中位年龄49.3岁（44 - 53.4岁）]。CD4细胞计数中位数为829（650 - 980），60%患有代谢综合征，18.5%患有糖尿病。BMI中位数为28.9（25.5 - 30.8）。有肝脂肪变性（任何级别）的患者与无脂肪变性的患者相比，更倾向于携带[此处原文缺失具体基因名称]的G等位基因变异[57.6%对16.7%（p = 0.09）]，但不包括[此处原文缺失具体基因名称]或[此处原文缺失具体基因名称]的变异。然而，患有脂肪性肝炎的患者与未患脂肪性肝炎的患者相比，显著更频繁地携带[此处原文缺失具体基因名称]的G等位基因变异[69.4%对39.1%（p < 0.05）]和[此处原文缺失具体基因名称]的A等位基因变异[75%对42%（p < 0.05）]。在我们的队列中，[此处原文缺失具体基因名称]基因变异与脂肪变性或脂肪性肝炎无关。[此处原文缺失具体基因名称]的G等位基因变异与脂肪性肝炎相关[比值比（OR）4.9（1.3 - 18）；p 0.02]和肝纤维化相关[OR 4.3（1.1 - 17.4）；p 0.04]，[此处原文缺失具体基因名称]的A等位基因变异与脂肪性肝炎相关[OR 6.6（1.6 - 27.6）；p 0.01]。[此处原文缺失具体基因名称]的G等位基因变异和[此处原文缺失具体基因名称]的A等位基因变异与转氨酶持续升高且患有NAFLD的PLWHIV患者的脂肪性肝炎和肝纤维化相关。我们建议对患有NAFLD的PLWHIV患者进行[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]的常规基因分型，以识别那些进展风险较高的患者。
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