Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA; Internal Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA.
Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.
J Hepatol. 2020 Mar;72(3):401-410. doi: 10.1016/j.jhep.2019.09.018. Epub 2019 Oct 4.
BACKGROUND & AIMS: Proof-of-concept studies frequently assess changes in intrahepatic triglyceride (IHTG) content by magnetic resonance-based techniques as a surrogate marker of histology. The aim of this study was to establish how reliable this strategy is to predict changes in liver histology in patients with non-alcoholic steatohepatitis (NASH).
Patients with NASH who had participated in our prior randomized controlled trials of pioglitazone with complete paired data for IHTG content by magnetic resonance spectroscopy and liver histology were included in the study.
A total of 121 patients were included. Changes in IHTG were assessed in several ways: as a continuous variable (correlations), as categorical groups (IHTG change ≥0%; or IHTG reduction of 1-30%; 31-50%; 51-70%; or >70%), and in a binomial way as steatosis resolution or not (defined as achieving IHTG <5.56%). Changes in IHTG correlated with steatosis on histology (r = 0.54; p <0.01). However, the magnitude of IHTG reduction was not associated with the rate of response of the primary histological outcome (2-point improvement in the NAFLD activity score from 2 different parameters, without worsening of fibrosis) or resolution of NASH without worsening of fibrosis, neither in patients receiving pioglitazone nor placebo. Changes in lobular inflammation, hepatocyte ballooning, or liver fibrosis were also independent of changes in IHTG, irrespective of treatment arm. Steatosis resolution was not associated with better histological outcomes either.
Changes in IHTG predict changes in steatosis but not of other liver histological parameters. This implies that IHTG response to treatment should be interpreted with caution, as it may not be as reliable as previously believed to predict a treatment's overall clinical efficacy in patients with NASH.
Quantification of liver fat by magnetic resonance imaging (MRI) is currently used to assess treatment responses in patients with fatty liver, with the assumption that improvements in liver fat translate into less inflammation, necrosis, and fibrosis in the liver. However, in this article, we showed that changes in liver fat do not necessarily translate into changes in these parameters. This means that MRI may not be as useful to assess treatment response in patients with fatty liver as previously believed.
基于磁共振的技术检测肝内甘油三酯（IHTG）含量的变化，通常被用作肝组织学的替代标志物来评估概念验证研究。本研究旨在确定这种策略在预测非酒精性脂肪性肝炎（NASH）患者的肝组织学变化方面的可靠性。
本研究纳入了曾参与我们先前关于吡格列酮的随机对照试验且具有完整的磁共振光谱法 IHTG 含量配对数据的 NASH 患者。
共纳入 121 例患者。通过以下几种方式评估 IHTG 的变化：作为连续变量（相关性）、分类组（IHTG 变化≥0%；或 IHTG 减少 1-30%；31-50%；51-70%；或>70%），以及二项方式作为脂肪变性是否缓解（定义为 IHTG<5.56%）。IHTG 的变化与肝组织学的脂肪变性相关（r=0.54；p<0.01）。然而，IHTG 减少的幅度与主要组织学终点的反应率（2 个不同参数的非酒精性脂肪性肝病活动评分的 2 点改善，纤维化无恶化）或无纤维化恶化的 NASH 缓解无关，无论患者接受吡格列酮还是安慰剂治疗。IHTG 的变化与小叶炎症、肝细胞气球样变或肝纤维化的变化也无关，与治疗臂无关。脂肪变性缓解也与更好的组织学结果无关。
IHTG 的变化可预测脂肪变性的变化，但不能预测其他肝组织学参数的变化。这意味着，IHTG 对治疗的反应应该谨慎解读，因为它可能不像之前认为的那样可靠，无法预测 NASH 患者治疗的整体临床疗效。
磁共振成像（MRI）定量检测肝脏脂肪目前用于评估脂肪肝患者的治疗反应，假设肝脏脂肪的改善会转化为肝脏炎症、坏死和纤维化的减少。然而，在本文中，我们表明，肝脏脂肪的变化不一定会转化为这些参数的变化。这意味着 MRI 可能不像之前认为的那样对评估脂肪肝患者的治疗反应有用。
