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Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background and Aims

The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C.

Methods

This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively.

Results

The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients.

Conclusion

The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.

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Abbreviations

APRI:

AST to platelet ratio index

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

ROC analysis:

Receiver operating characteristic analysis

References

  1. Seto WK, Lo YR, Pawlotsky JM, et al. Chronic hepatitis B virus infection. Lancet. 2018;392:2313–24.

    Article  Google Scholar 

  2. Trivedi HD, Patwardhan VR, Malik R. Chronic hepatitis C infection—Noninvasive assessment of liver fibrosis in the era of direct acting antivirals. Dig Liver Dis. 2019;51:183–9.

    Article  Google Scholar 

  3. Singh S, Muir AJ, Dieterich DT, et al. American Gastroenterological Association Institute technical review on the role of elastography in chronic liver diseases. Gastroenterology. 2017;152:1544–77.

    Article  Google Scholar 

  4. World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/. Accessed 31 July 2020.

  5. World Health Organization. Guidelines for the screening, care and treatment of persons with hepatitis C infection. https://www.who.int/hiv/pub/hepatitis/hepatitis-c-guidelines/en/. Accessed 31 July 2020.

  6. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560–99.

    Article  Google Scholar 

  7. AASLD-IDSA Hepatitis C Guidance Panel. Hepatitis C Guidance. Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2019;2020(71):686–721.

    Google Scholar 

  8. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.

    Article  Google Scholar 

  9. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69:461–511.

    Article  Google Scholar 

  10. Japanese Guideline for Management of Hepatitis B ver 3.1 (written in Japanese). The Japan Society of Hepatology. 2019. https://www.jsh.or.jp/medical/guidelines/jsh_guidlines/hepatitis_b. Accessed 31 July 2020.

  11. Japanese Guideline for Management of Hepatitis C ver 7 (written in Japanese). The Japan Society of Hepatology. 2019. http://www.jsh.or.jp/medical/guidelines/jsh_guidlines/hepatitis_c. Accessed 31 July 2020.

  12. Papastergiou V, Tsochatzis E, Burroughs AK. Non-invasive assessment of liver fibrosis. Ann Gastroenterol. 2012;25:218–31.

    PubMed  PubMed Central  Google Scholar 

  13. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol. 2014;61:S58-68.

    Article  Google Scholar 

  14. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  Google Scholar 

  15. Lu M, Li J, Zhang T, Chronic hepatitis cohort study investigators, et al. Serum biomarkers indicate long-term reduction in liver fibrosis in patients with sustained virological response to treatment for HCV infection. Clin Gastroenterol Hepatol. 2016;14:1044-1055.e3.

    Article  Google Scholar 

  16. Schmid P, Bregenzer A, Huber M, Swiss HIV cohort study, et al. Progression of liver fibrosis in HIV/HCV co-infection: a comparison between non-invasive assessment methods and liver biopsy. PLoS ONE. 2015;10:e0138838.

    Article  Google Scholar 

  17. Hiramatsu N, Hayashi N, Kasahara A, et al. Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol. 1995;22:135–42.

    Article  CAS  Google Scholar 

  18. Elsharkawy A, Alem SA, Fouad R, et al. Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon. J Gastroenterol Hepatol. 2017;32:1624–30.

    Article  CAS  Google Scholar 

  19. Xiao G, Yang J, Yan L. Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta-analysis. Hepatology. 2015;61:292–302.

    Article  Google Scholar 

  20. Xu XY, Kong H, Song RX, et al. The effectiveness of noninvasive biomarkers to predict hepatitis B-related significant fibrosis and cirrhosis: a systematic review and meta-analysis of diagnostic test accuracy. PLoS ONE. 2014;9:e100182.

    Article  Google Scholar 

  21. Xu XY, Wang WS, Zhang QM, et al. Performance of common imaging techniques vs serum biomarkers in assessing fibrosis in patients with chronic hepatitis B: A systematic review and meta-analysis. World J Clin Cases. 2019;7:2022–37.

    Article  Google Scholar 

  22. Zhang Z, Wang G, Kang K, et al. The diagnostic accuracy and clinical utility of three noninvasive models for predicting liver fibrosis in patients with HBV infection. PLoS ONE. 2016;11:e0152757.

    Article  Google Scholar 

  23. Li Q, Ren X, Lu C, et al. Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN: A retrospective cohort study. Medicine (Baltimore). 2017;96:e6336.

    Article  CAS  Google Scholar 

  24. Sanai FM, Farah T, Albeladi K, et al. Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B. BMC Gastroenterol. 2017;17:101.

    Article  Google Scholar 

  25. Kim WR, Berg T, Asselah T, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. J Hepatol. 2016;64:773–80.

    Article  CAS  Google Scholar 

  26. Stasi C, Salomoni E, Arena U, et al. Non-invasive assessment of liver fibrosis in patients with HBV-related chronic liver disease undergoing antiviral treatment: a preliminary study. Eur J Pharmacol. 2017;806:105–9.

    Article  CAS  Google Scholar 

  27. Li J, Gordon SC, Rupp LB, et al. CHeCS Investigators. Long-term progression of viral load and serum markers of fibrosis among treated and untreated patients with chronic hepatitis B. J Gastroenterol Hepatol. 2017;32:1250–7.

    Article  CAS  Google Scholar 

  28. Graf C, Mondorf A, Knop V, et al. Evaluation of point shear wave elastography using acoustic radiation force impulse imaging for longitudinal fibrosis assessment in patients with HBeAg-negative HBV infection. J Clin Med. 2019;8:2101.

    Article  CAS  Google Scholar 

  29. Patel K, Sebastiani G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Rep. 2020;2:100067.

    Article  Google Scholar 

  30. Hagström H, Talbäck M, Andreasson A, et al. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease. J Hepatol. 2020;73:1023–9.

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to the doctors in the following institutes for their support during this study: the Hospital of Hyogo College of Medicine, Hiroshima University Hospital, Hokkaido University Hospital, Yamagata University Hospital, University of Yamanashi Hospital, Osaka City University Hospital, Kumamoto University Hospital, and Kurume University Hospital.

Funding

This work was supported by the Japan Agency for Medical Research and Development. This study was conducted as a part of the Policy Research for Hepatitis Measures of the Ministry of Health, Labor and Welfare in Japan and was supported by Health, Labour and Welfare Sciences Research Grants in Japan (Grant number H29- kansei-shitei-001 and 20HC2002).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Jun Itakura, Masayuki Kurosaki & Namiki Izumi

  2. Department of Gastroenterology and Hepatology, Kumamoto Rosai Hospital, Yatsushiro, Japan

    Hiroko Setoyama

  3. Department of Gastroenterology, Saga Medical Center Kouseikan, Saga, Japan

    Tetsuro Simakami & Shuichi Kaneko

  4. Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

    Noriko Oza

  5. Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan

    Masaaki Korenaga & Tatsuya Kanto

  6. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

    Motohiko Tanaka

  7. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

    Takuji Torimura

  8. Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Naoya Sakamoto

  9. First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

    Nobuyuki Enomoto

  10. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yoshiyuki Ueno

  11. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Norifumi Kawada

  12. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan

    Shuhei Nishiguchi

  13. Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Kazuaki Chayama

  14. Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Junko Tanaka

Authors
  1. Jun Itakura
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  2. Masayuki Kurosaki
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  17. Namiki Izumi
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Contributions

Conceptualization: JI, MK and TK. Methodology: JI, MK and TK. Formal analysis: JI. Investigation: JI, HS, NO and MK. Resources: JI, HS, TS, NO, MK, MT, TT, NS, NE, YU, NK, SK, SN, KC, and JT. Data curation: JI, HS. Writing (original draft preparation): JI. Writing (review and editing): MK and TK. Supervision: MK and TK. Project administration: TK. Funding acquisition: TK.

Corresponding author

Correspondence to Tatsuya Kanto.

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Itakura, J., Kurosaki, M., Setoyama, H. et al. Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis. J Gastroenterol 56, 470–478 (2021). https://doi.org/10.1007/s00535-021-01782-3

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  • DOI: https://doi.org/10.1007/s00535-021-01782-3

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