Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Clin Infect Dis. 2021 Jun 15;72(12):2087-2094. doi: 10.1093/cid/ciaa382.
Nonalcoholic fatty liver disease (NAFLD) affects more than one-third of people living with human immunodeficiency virus (HIV). Nonetheless, its natural history is poorly understood, including which patients are most likely to have a progressive disease course.
We leveraged a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months with serial biopsies.
In all participants with baseline biopsies (n = 58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (mean ± standard deviation [SD], 3.6 ± 2.0 vs 2.0 ± 0.8; P < .0001) and visceral fat content (mean ± SD, 284 ± 91 cm2 vs 212 ± 95 cm2; P = .005), but no difference in hepatic fat or body mass index. Among placebo-treated participants with paired biopsies (n = 24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, odds of fibrosis progression increased by 37% (odds ratio, 1.37 [95% confidence interval, 1.03-2.07]). There was no difference in baseline NAS between fibrosis progressors and nonprogressors, though NAS rose over time in the progressor group (mean ± SD, 1.1 ± 0.8 vs -0.5 ± 0.6; P < .0001).
In this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel predictor of worsening fibrosis. In contrast, baseline histologic characteristics did not relate to fibrosis progression.
非酒精性脂肪性肝病（NAFLD）影响超过三分之一的人类免疫缺陷病毒（HIV）感染者。尽管如此，其自然病史仍知之甚少，包括哪些患者最有可能出现疾病进展。
我们利用生长激素释放激素类似物 tesamorelin 治疗 HIV 相关性 NAFLD 的随机试验。61 名 HIV 相关性 NAFLD 患者被随机分为 tesamorelin 或安慰剂组，治疗 12 个月，并进行系列肝活检。
在所有基线肝活检的参与者中（n=58），43%有肝纤维化。有纤维化的个体有更高的 NAFLD 活动评分（NAS）（平均值±标准差[SD]，3.6±2.0 与 2.0±0.8；P<0.0001）和内脏脂肪含量（平均值±SD，284±91cm2 与 212±95cm2；P=0.005），但肝脂肪和体重指数没有差异。在接受配对肝活检的安慰剂治疗参与者中（n=24），38%在 12 个月内有肝纤维化进展。基线内脏脂肪每增加 25cm2，纤维化进展的几率增加 37%（比值比，1.37[95%置信区间，1.03-2.07]）。纤维化进展者和非进展者的基线 NAS 没有差异，但进展者组的 NAS 随时间升高（平均值±SD，1.1±0.8 与-0.5±0.6；P<0.0001）。
在这项 HIV 相关性 NAFLD 的纵向研究中，观察到了很高的肝纤维化和进展率。内脏脂肪被确定为纤维化恶化的新预测因子。相比之下，基线组织学特征与纤维化进展无关。
