How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy
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To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM).
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.
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.
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.
• 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.
KeywordsSonoelastography Diagnostic ultrasound Liver fibrosis Bilirubin Hepatitis B virus infection
2D shear wave elastography
Serum alkaline phosphatase
Body mass index
chronic hepatitis B
Hepatitis B virus
Liver stiffness measurements
Receiver operating characteristic
Upper limit of normal
The authors thank Caixia Zhang (School of Public Health, Sun Yat-sen University) who helped with the statistics.
This study received financial support from the National Natural Science Foundation of China (No. 81601503) and the National Key Research and Development Program of China (No. 2017YFC0112000).
Compliance with ethical standards
The scientific guarantor of this publication is Rong-Qin Zheng.
Conflict of interest
All authors disclosed no relevant relationships of conflict of interest.
Statistics and biometry
Darrell R. Schroeder (Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester MN) and Caixia Zhang (School of Public Health, Sun Yat-sen University) kindly provided statistical advice for this manuscript.
Written informed consent was obtained from all subjects in this study.
Institutional Review Board approval was obtained.
Study subjects or cohorts overlap
Some study subjects have been previously reported in two articles entitled “Diagnostic accuracy of two-dimensional shear wave elastography for the non-invasive staging of hepatic fibrosis in chronic hepatitis B: a cohort study with internal validation” and “Shear wave elastography for liver fibrosis in chronic hepatitis B: Adapting the cut-offs to alanine aminotransferase levels improves accuracy.”
• Diagnostic or prognostic study
• Performed at one institution
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