Department of Hepato-Gastroenterology, Amiens University Hospital, Amiens, France; Inserm UMR 1247 GRAP (Groupe de Recherche sur l'Alcool et les Pharmacodependance), Université de Picardie Jules Verne, Amiens, France.
Department of Gastroenterology and Hepatology and Odense Patient Data Exploratory Network at Odense University Hospital, Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
Lancet Gastroenterol Hepatol. 2018 Sep;3(9):614-625. doi: 10.1016/S2468-1253(18)30124-9. Epub 2018 Jul 6.
The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness.
We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis.
Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79-0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82-0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86-0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83-0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both.
This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs.
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瞬时弹性成像在非侵入性诊断酒精性肝纤维化方面的价值存在争议。我们进行了一项个体患者数据（IPD）荟萃分析，以确定酒精性纤维化中肝脏硬度的特定诊断截止值，并评估天冬氨酸转氨酶（AST）浓度、胆红素浓度以及无症状和非严重酒精性肝炎的存在对肝硬度的影响。
我们在 PubMed 中搜索了包含酒精性肝病、肝活检和瞬时弹性成像的患者的研究，并采用基于 FibroScan 结果确定酒精性肝纤维化诊断截止值的统计方法，检索时间为 2000 年 1 月 1 日至 2017 年 9 月 30 日。从相应的作者处获得了原始数据库，以 Excel 表格的形式呈现。在两阶段随机效应荟萃分析中确定了不同纤维化阶段的汇总诊断截止值。在单阶段随机效应荟萃分析中评估了 AST 浓度、胆红素浓度以及无症状和非严重酒精性肝炎的组织学特征对肝硬度截止值的影响。
在评估的 188 项研究中，有 10 项研究共纳入 1026 例患者纳入荟萃分析，得出了以下肝脏硬度截止值：F≥1 纤维化的 7.0 kPa（受试者工作特征曲线下面积 0.83 [SE 0.02；95%CI 0.79-0.87]），F≥2 的 9.0 kPa（0.86 [0.02；0.82-0.90]），F≥3 的 12.1 kPa（0.90 [0.02；0.86-0.94]）和 F=4 的 18.6 kPa（0.91 [0.04；0.83-0.99]）。AST 和胆红素浓度对肝硬度有显著影响，浓度越高，肝硬度值越高（p<0.0001），且所有纤维化阶段（但 F≥1）的诊断截止值也显著升高。无症状和非严重酒精性肝炎的组织学特征与肝硬度增加有关（p<0.0001）。在多变量分析中，AST（p<0.0001）和胆红素（p=0.0002）浓度以及凝血酶原活动度（p=0.01）与无症状和非严重酒精性肝炎的组织学特征独立相关。最后，根据 AST 和胆红素浓度确定了特定的肝硬度截止值。AST 浓度升高、胆红素浓度升高或两者兼有的患者，肝硬度截止值升高。
这项 IPD 荟萃分析强调了肝硬度与无症状和非严重酒精性肝炎的组织学特征之间的联系，这反映在 AST 和胆红素浓度上。在酒精性肝病中，FibroScan 对肝纤维化的评估应通过使用专门调整的肝硬度截止值来考虑 AST 和胆红素浓度。
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