title: A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection.
abstract: Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV-infected and treatment-naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty-nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma-glutamyltransferase-to-platelet ratio (GPR), red cell volume distribution width-to-platelet ratio (RPR), FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB-4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR-HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR-HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment-naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Zhu
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: D-M
authors.initials: DM
authors.lastname: Yu
authors.affiliation: Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Z-T
authors.initials: ZT
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: J
authors.identifier: 0000-0002-5847-4888
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Q-M
authors.initials: QM
authors.lastname: Gong
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: D-H
authors.initials: DH
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.|Collaborative Innovation Center of Systems Biomedicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: P-Z
authors.initials: PZ
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: X-X
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers
keywords: blood biomarkers; chronic hepatitis B virus infection; diagnosis; liver fibrosis