OBJECTIVES To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). METHODS Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. RESULTS Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46 kPa for ≥ F2, 10.94 kPa for ≥ F3, and 15.88 kPa for F4, than those with normal TB (7.62 kPa, 8.26 kPa, and 11.01 kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. CONCLUSION Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. KEY POINTS • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.

中文翻译：

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肝内胆汁淤积如何影响慢性乙型肝炎患者的肝脏僵硬：一项对1197例肝活检患者的研究。

目的使用肝硬度测量（LSM）评估肝内胆汁淤积对肝纤维化分期的影响。方法在2011年7月至2016年9月之间，共纳入1197例慢性乙型肝炎（CHB）感染患者，以收集临床，生物学，二维切波弹性成像（SWE）和组织学（METAVIR评分系统）数据。在每组纤维化阶段，丙氨酸转氨酶（ALT）水平和炎症等级的每组中，将正常总胆红素（TB）与异常结核患者的LSM进行比较。进行逻辑回归和ROC分析以评估增加TB和LSM对纤维化分期的益处。结果分析了793例患者。在相同的纤维化阶段，结核病异常患者的LSMs值显着高于正常结核病患者。通常在不同亚组的患者中发现异常结核的LSM升高（≤F2或≥F3; ALT <2×正常上限（ULN）或ALT≥2×ULN; METAVIR活动度≤1或≥2）。结核水平异常的患者显示出更高的最佳临界值：≥F2的患者为10​​.46 kPa，≥F3的患者为10​​.94 kPa，F4的患者为15.88 kPa，而结核病正常的患者则分别为7.62 kPa，8.26 kPa和11.01 kPa。LSM评估的纤维化分期（≥F2，≥F3，F4）显示，结核病水平异常的患者（44.6％，45.1％，39.6％）的假阳性率高于正常结核病患者（20.7％，17.1％，14.4％）。然而，当在纤维化阶段将TB添加到LSM中时，ROC曲线下的面积没有明显改变。结论肝内胆汁淤积对CHB患者的LSM影响不大，也导致对肝纤维化阶段的高估。但是，在LSM中增加TB水平并不能改善肝纤维化阶段的整体诊断性能。要点•肝内胆汁淤积对慢性HBV患者的肝硬度测量（LSM）表现出轻微影响。•总胆红素（TB）水平异常的患者表现出较高的最佳临界值和假阳性率。•当考虑肝内胆汁淤积时，LSM对慢性HBV感染患者肝纤维化分期的诊断性能不会提高。