Estimation of Liver Fibrosis by Noncommercial Serum Markers in Comparison With Transient Elastography in Patients With Chronic Hepatitis C Virus Infection Receiving Direct-acting Antiviral Treatment

Viola Knop; Wolf P. Hofmann; Peter Buggisch; Hartwig Klinker; Stefan Mauss; Rainer Günther; Holger Hinrichsen; Dietrich Hüppe; Heike Pfeiffer-Vornkahl; Karl-Georg Simon; Thomas Berg; Michael P. Manns; Mireen Friedrich-Rust; German Hepatitis C-Registry


J Viral Hepat. 2019;26(2):224-230. 

In This Article

Abstract and Introduction


Treatment decisions are based on extent of fibrosis in patients with chronic hepatitis C (HCV) infection. Noninvasive diagnostic tools may help to avoid liver biopsy. We investigated the diagnostic accuracy of noncommercial serum scores in comparison with transient elastography (TE). Data analysis was undertaken based on 2458 patients enrolled in the German Hepatitis C Registry, in a prospective, observational study. Aspartate aminotransferase-to-platelet ratio index (APRI), FORNS index and FIB-4 score were calculated and the diagnostic accuracy was compared to TE. As estimated by TE, 955 (38.9%) patients had absence of significant fibrosis (SF), 736 (29.9%) patients had SF, and 767 (31.2%) patients were shown to have cirrhosis. Patients with absence of SF had a sustained virological response (SVR) rate of 97.9%, whereas SVR was attained in 96.2% and 92.2% in those with SF and cirrhosis, respectively (P < 0.0001). The area under the receiver operator characteristic curve (AUROC), sensitivity and specificity in discriminating of SF were 0.789, 0.596 and 0.939 by APRI; 0.838, 0.852 and 0.748 by FORNS index; and 0.828, 0.658 and 0.946 by FIB-4 score. AUROCs for the prediction of cirrhosis, sensitivity and specificity were 0.881, 0.851 and 0.854 by APRI; 0.846, 0.948 and 0.628 by FORNS index; and 0.907, 0.907 and 0.848 by FIB-4 score. In conclusion, in the present multicentre real-world cohort, SF and cirrhosis were predicted with high accuracy with noncommercial serum markers using TE as reference. Further prospective long-term follow-up is necessary to compare biomarkers with TE concerning liver-related outcome and overall mortality.


Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide.[1,2] The extent of hepatic fibrosis, a predictor of disease progression, determines the need for antiviral treatment and may help to select the optimal duration of therapy as well as the most appropriate regimen.[3–5] Liver biopsy, the so-called gold standard for staging of fibrosis, is invasive, and the accuracy is suboptimal due to sampling variations, inadequate specimen size and observer variability.[6] Furthermore, the dynamic process of liver fibrosis resulting from progression and regression cannot be simply quantified by biopsy. These limitations have stimulated the development of noninvasive tools for the indirect assessment of fibrosis.[7,8] In recent years, multiple studies and consecutive meta-analyses[9–11] have evaluated transient elastography (TE) for the diagnosis of liver fibrosis. The authors demonstrated that liver stiffness (LS) values strongly correlated with METAVIR fibrosis stages, whereas detection of cirrhosis was shown to be more accurate (AUROC values 0.80–0.99) than significant fibrosis (AUROC values 0.65–0.97). Recent guidelines recommend the use of TE for liver fibrosis staging prior to therapy in HCV-infected patients.[12–14] Liver biopsy may be required in cases of suspected mixed aetiologies.[11] Moreover, a variety of serum biomarkers have been proposed for staging liver fibrosis, currently the most validated being the AST-to-platelet ratio index (APRI), FORNS index, FIB-4 score and Fibrotest.[15–19] The advantages of serum markers to detect fibrosis are their high applicability, their good inter-laboratory reproducibility and, if nonpatented, their potential widespread availability.[12] A recent systematic review including 172 studies conducted in hepatitis C reported median AUROCs of 0.77 and 0.84 for APRI, for significant fibrosis (F2-F4) and cirrhosis (F4), respectively.[20] Another meta-analysis evaluated results from 6259 HCV-infected patients from 33 studies taking liver biopsy as reference; the mean AUROC values of APRI in diagnosis of significant fibrosis and cirrhosis were 0.77 and 0.83, respectively.[21] Several studies have compared the performances of TE and serum biomarkers.[22–24] Both procedures have been shown to have equivalent performance for the diagnosis of significant fibrosis (F2-F4), but TE was superior in detecting cirrhosis (F4).

Real-world data comparing different techniques of noninvasive assessment of liver fibrosis are currently limited. However, it is highly important to analyse whether results of a clinical trial could be translated into daily clinical practice and may offer guidance in decision-making.

In the present study, we investigated the diagnostic accuracy of a panel of noncommercial serum scores in comparison with transient elastography in patients enrolled into the German Hepatitis C Registry, a prospective multicentre observational cohort study.