Lin S C, Heba E, Bettencourt R, Lin G Y, Valasek M A, Lunde O, Hamilton G, Sirlin C B, Loomba R
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.
Aliment Pharmacol Ther. 2017 Mar;45(6):844-854. doi: 10.1111/apt.13951. Epub 2017 Jan 24.
Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally.
To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial.
This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained.
Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV.
The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.
磁共振成像衍生的肝脏脂肪和体积测量正逐渐成为非酒精性脂肪性肝炎（NASH）中准确的非侵入性成像生物标志物。纵向来看，对于这些测量指标与组织学之间的关系知之甚少。
在一项NASH试验中，研究磁共振成像衍生的质子密度脂肪分数（PDFF）、全肝体积（TLV）、全肝脂肪指数（TLFI）与组织学之间的关系。
这是一项对50例经活检证实为NASH患者进行的为期24周的随机、双盲、安慰剂对照试验的二次分析，患者被随机分为每日口服依泽替米贝10 mg组（n = 25）和安慰剂组（n = 25）。获取了基线和治疗后的人体测量学数据、生化指标、磁共振成像和活检结果。
基线时平均PDFF与TLFI密切相关（Spearman秩相关系数ρ = 0.94，n = 45，P < 0.0001），与TLV也有良好的相关性（ρ = 0.57，n = 45，P < 0.0001）。平均TLV与TLFI密切相关（ρ = 0.78，n = 45，P < 0.0001）。24周后，PDFF与TLFI仍密切相关（ρ = 0.94，n = 45，P < 0.0001），与TLV保持良好的相关性（ρ = 0.51，n = 45，P = 0.0004）。TLV与TLFI仍密切相关（ρ = 0.74，n = 45，P < 0.0001）。1级与3级脂肪变性患者的PDFF、TLV和TLFI较低（分别为P < 0.0001、P = 0.0003、P < 0.0001）。MRI-PDFF与TLV变化的回归分析表明，MRI-PDFF降低10%可预测TLV减少257 mL。
MRI-PDFF和TLV与TLFI密切相关。脂肪变性的减轻与肝肿大的改善相关。这些测量指标值较低反映了较低的组织学脂肪变性分级。在NASH试验中，磁共振成像衍生的肝脏脂肪和体积测量指标可能比组织学更具动态性且更灵敏，可作为成像生物标志物。
