Progression of the FIB-4 index among patients with chronic HCV infection and early liver disease

Lisette A.P. Krassenburg, Raoel Maan, Amy Puenpatom, Nicole S. Erler, Christoph Welsch, Stijn van Hees, Orlando Cerrhoci, Johannes Vermehren, Robert J. de Knegt, Bettina E. Hansen, Stefan Zeuzem, Thomas Vanwolleghem, Harry L.A. Janssen, Robert A. de Man, Jordan J. Feld, Adriaan J. van der Meer*

*Corresponding author for this work

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Background and aims:

Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease. 

Methods and results:

Patients diagnosed with chronic HCV and FIB-4 <3.25 from four international liver clinics were included in a retrospective cohort study. Follow-up ended at start of antiviral therapy resulting in sustained virological response, at time of liver transplantation or death. Primary outcome of advanced liver disease was defined as FIB-4 >3.25 during follow-up. Survival analyses were used to assess time to FIB-4 >3.25. In total, 4286 patients were followed for a median of 5.0 (IQR 1.7-9.4) years, during which 41 071 FIB-4 measurements were collected. At baseline, median age was 47 (IQR 39-55) years, 2529 (59.0%) were male, and 2787 (65.0%) patients had a FIB-4 <1.45. Advanced liver disease developed in 821 patients. Overall, 10-year cumulative incidence of advanced disease was 32.1% (95% CI 29.9% to 34.3%). Patients who developed advanced disease showed an exponential FIB-4 increase. Among patients with a presumed date of HCV infection, cumulative incidence of advanced disease increased 7.7-fold from 20 to 40 years as opposed to the first 20 years after HCV infection. 


The rate of advanced liver disease is high among chronic HCV-infected patients with early disease at time of diagnosis, among whom liver disease progression accelerated over time. These results emphasise the need to overcome any limitations with respect to diagnosing and treating all patients with chronic HCV across the globe.

Original languageEnglish
Article numbere001209
JournalBMJ Open Gastroenterology
Issue number1
Publication statusPublished - 7 Dec 2023

Bibliographical note

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


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