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. 2025 Mar 20;25(1):191.
doi: 10.1186/s12876-025-03770-w.

Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with concurrent liver diseases

Pan Yan #  1 , Xiaoping Yu #  2 , Zhu Chen #  3 , Lijuan Lan  4 , Jun Kang  4 , Bennan Zhao  4 , Dafeng Liu  5   6
Affiliations

Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with concurrent liver diseases

Pan Yan et al. BMC Gastroenterol. .

Abstract

Objective: This study investigated the consistency of the FIB-4, APRI, and GPR indices in assessing significant liver fibrosis and cirrhosis in patients with Coronavirus Disease 2019(COVID-19) who also suffer from various liver diseases, providing references for the clinical selection and application for non-invasive assessment methods.

Methods: The study evaluated 744 COVID-19 patients with coexisting liver diseases: 508 cases with non-alcoholic fatty liver disease (NAFLD), 158 cases with chronic hepatitis B (CHB), and 78 cases with a combination of both ailments. FIB-4, APRI, and GPR were employed to assess significant liver fibrosis and cirrhosis. Concordance among the methods was determined using Kappa analysis, and receiver operating characteristic (ROC) curves helped identify the optimal cutoff values for each index.

Results: For COVID-19 patients with NAFLD, Kappa values for significant liver fibrosis were 0.81, 0.90, 0.80, and 0.79, and for cirrhosis, they were 0.88, 0.97,0.88, and 0.88, respectively (all p < 0.05). Among those with CHB, Kappa values were 0.81, 0.81, 0.83, and 0.75 for fibrosis, and0.87, 0.91, 0.88, and 0.92 for cirrhosis (all p < 0.05). In patients with coexisting liver diseases, the values were 0.87, 0.86, 0.86, and 0.78 for fibrosis, and 0.67, 0.69, 0.54, and 0.81for cirrhosis (all p < 0.05). Linear trend analysis revealed significant relationships between FIB-4 values, APRI values, GPR values, and the severity of COVID-19 (χ2 trend: 15.205,35.114, and 13.973, respectively, all p < 0.001), between FIB-4 values and APRI values and the coronavirus negative conversion time (all p < 0.05) in COVID-19 with NAFLD, and between FIB-4 values and GPR values and the coronavirus negative conversion time in patients with COVID-19 with CHB(all p < 0.05).

Conclusion: Using the current cutoff values, the non-invasive assessments demonstrated almost perfect consistency in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with liver diseases, though FIB-4 and GPR showed moderate consistency in cirrhosis evaluation in patients with coexisting liver conditions. Moreover, it also indicated that increased liver fibrosis correlates with more severe COVID-19 and prolonged coronavirus negative conversion time.

Keywords: Chronic hepatitis B(CHB); Cirrhosis; Coronavirus disease 2019(COVID-19); Kappa value; Liver fibrosis; Non-alcoholic fatty liver disease(NAFLD); Non-invasive assessment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki ( https://www.wma.net/policies-post/wma-declaration-of- helsinki/). Ethical approval for this research was obtained from the Ethics Committee of the Public Health and Clinical Center of Chengdu (No.: PJ-K2020-26-01). The ethics committee/institutional review board waived the requirement for written informed consent from the participants or their legal guardians/next of kin due to the retrospective nature of the study, the use of anonymized data, and the provision of comprehensive verbal and written information to all patients regarding the study’s purpose and potential implications. The study was conducted in accordance with local legislation and institutional requirements. Consent for publication: All of the participants understand that the information will be published without their child or ward’s/their relative’s (circle as appropriate) name attached but that full anonymity cannot be guaranteed. All of the participants understand that the text and any pictures or videos published in the article will be freely available on the internet and may be seen by the general public. The pictures, videos and text may also appear on other websites or in print and may be translated into other languages or used for commercial purposes. All of the participants were offered the opportunity to read the manuscript. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Analysis of liver enzymes at admission in patients with COVID-19 combined with different liver diseases. ***P <0.001; aP <0.05; bP <0.001, compared with COVID-19 patients and CHB
Fig. 2
Fig. 2
FIB-4, APRI, and GPR values impacting on disease severity of COVID-19 patients. (a–c): Effect on FIB-4, APRI, and GPR in COVID-19 with NAFLD. (d–f): Effect on FIB-4, APRI, and GPR in COVID-19 with CHB. (g–i): Effect on FIB-4, APRI, and GPR in COVID-19 with NAFLD-CHB. 0: Asymptomatic; 1: Mild; 2: Moderate; 3: Severe. **P <0.01; ***P <0.001. ap<0.05, bp<0.01, compared with Asymptomatic cp<0.05, dp<0.01, compared with Mild
Fig. 3
Fig. 3
Impact of FIB-4, APRI, and GPR on coronavirus negative conversion time (a, b): Effects of FIB-4 and APRI on coronavirus negative conversion time in COVID-19 with NAFLD. (c, d): Effects of FIB-4 and GPR on coronavirus negative conversion time in COVID-19 with CHB. < F2: non-significant liver fibrosis; ≥F2: significant liver fibrosis; ≥F4: cirrhosis. *P <0.05,***P<0.001
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