Skip to main content
SpringerLink
Log in

Serum rheumatoid factor is correlated with liver fibrosis in patients with chronic hepatitis B

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Background and aim

Non-invasive methods are being developed to evaluate liver fibrosis. In this study, we aimed to evaluate the diagnostic performance of rheumatoid factor (RF) to predict liver fibrosis in chronic hepatitis B (CHB).

Methods

A total of 235 non-arthritic, treatment-naive patients with hepatitis B virus (HBV) were enrolled in this study. The RF level was analyzed concurrently with HBV-DNA and routine biochemical tests. The liver biopsies were scored by using the Knodell modified histology activity index (HAI) and the Ishak fibrosis score.

Results

Mean age, ALT, AST, ALP, GGT, INR, and HBV-DNA levels were significantly higher, and mean albumin and platelet levels were significantly lower in the RF positive group than the RF negative group. Liver biopsy was performed in 112 (47.66%) patients, and the RF positivity rate was 18 (15.38%) in the infection subgroup and 73 (61.86%) in the hepatitis subgroup. Along with the RF positivity rate, the fibrosis and HAI scores were also increased. A high fibrosis score is associated with a high RF positivity rate.

Conclusions

In the current study, we found that there was a significant positive correlation between RF and liver fibrosis stage in patients with CHB. The RF that is easily obtained with low cost may be considered as an alternative biomarker for predicting liver fibrosis in CHB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AFP:

Alpha-fetoprotein

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

APRI:

AST to platelet ratio index

CHB:

Chronic hepatitis B

ELISA:

Enzyme-linked immunosorbent assay

FIB‑4:

Fibrosis‑4

GGT:

Gamma-glutamyltransferase

HAI:

Histology activity index

HBV:

Hepatitis B virus

HBeAg:

Hepatitis B envelope antigen

HBsAg:

Hepatitis B surface antigen

Ig:

Immunoglobulin

INR:

International normalized ratio

PCR:

Polymerase chain reaction

RF:

Rheumatoid factor

ROC:

Receiver operating characteristic

TLR:

Toll-like receptors

References

  1. 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 

  2. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500.

    Article  CAS  Google Scholar 

  3. Agbim U, Asrani SK. Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers. Expert Rev Gastroenterol Hepatol. 2019;13:361–74.

    Article  CAS  Google Scholar 

  4. Park SH, Kim CH, Kim DJ, Suk KT, Cheong JY, Cho SW, et al. Usefulness of multiple biomarkers for the prediction of significant fibrosis in chronic hepatitis B. J Clin Gastroenterol. 2011;45:361–5.

    Article  CAS  Google Scholar 

  5. Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142:1293–1302.e4.

    Article  Google Scholar 

  6. Castera L, Pinzani M. Non-invasive assessment of liver fibrosis: are we ready? Lancet. 2010;375:1419–20.

    Article  Google Scholar 

  7. Parsian H, Rahimipour A, Nouri M, Somi MH, Qujeq D. Assessment of liver fibrosis development in chronic hepatitis B patients by serum hyaluronic acid and laminin levels. Acta Clin Croat. 2010;49:257–65.

    PubMed  Google Scholar 

  8. Cales P, Veillon P, Konate A, Mathieu E, Ternisien C, Chevailler A, et al. Reproducibility of blood tests of liver fibrosis in clinical practice. Clin Biochem. 2008;41:10–8.

    Article  Google Scholar 

  9. Soltys AI, Axford JS, Sutton BJ. Rheumatoid factors: where are we now? Ann Rheum Dis. 1997;56:285–6.

    Article  CAS  Google Scholar 

  10. Mewar D, Wilson AG. Autoantibodies in rheumatoid arthritis: a review. Biomed Pharmacother. 2006;60:648–55.

    Article  CAS  Google Scholar 

  11. Penaranda-Parada E, Quintana G, Yunis JJ, Mantilla R, Rojas W, Panqueva U, et al. Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population. Lupus. 2015;24:1293–9.

    Article  CAS  Google Scholar 

  12. Pertovaara M, Pukkala E, Laippala P, Miettinen A, Pasternack A. A longitudinal cohort study of Finnish patients with primary Sjogren’s syndrome: clinical, immunological, and epidemiological aspects. Ann Rheum Dis. 2001;60:467–72.

    Article  CAS  Google Scholar 

  13. Singer JM, Plotz CM, Perlata FM, Lyons HC. The presence of anti-gamma globulin factors in sera of patients with active pulmonary tuberculosis. Ann Intern Med. 1962;56:545–52.

    Article  CAS  Google Scholar 

  14. Oreskes I, Siltzbach LE. Changes in rheumatoid factor activity during the course of sarcoidosis. Am J Med. 1968;44:60–7.

    Article  CAS  Google Scholar 

  15. Cerny EH, Farshy CE, Hunter EF, Larsen SA. Rheumatoid factor in syphilis. J Clin Microbiol. 1985;22:89–94.

    Article  CAS  Google Scholar 

  16. Lienesch D, Morris R, Metzger A, Debuys P, Sherman K. Absence of cyclic citrullinated peptide antibody in nonarthritic patients with chronic hepatitis C infection. J Rheumatol. 2005;32:489–93.

    PubMed  Google Scholar 

  17. Choi ST, Lee HW, Song JS, Lee SK, Park YB. Analysis of rheumatoid factor according to various hepatitis B virus infectious statuses. Clin Exp Rheumatol. 2014;32:168–73.

    CAS  PubMed  Google Scholar 

  18. Watanabe K, Ohkubo Y, Funahashi Y, Nishimaki T, Moritoh T, Kasukawa R, et al. An investigation on rheumatoid factor of different immunoglobulin classes in hepatitis B virus carriers. Clin Rheumatol. 1991;10:31–7.

    Article  CAS  Google Scholar 

  19. Lee SI, Yoo WH, Yun HJ, Kim DS, Lee HS, Choi SI, et al. Absence of antibody to cyclic citrullinated peptide in sera of non-arthritic patients with chronic hepatitis B virus infection. Clin Rheumatol. 2007;26:1079–82.

    Article  Google Scholar 

  20. Hoofnagle JH, Markenson JA, Daniels CA, Gerety RJ, Notkins AL, Barker LF. The lack of association between rheumatoid factor and hepatitis B antigen. Am J Med Sci. 1974;268:23–9.

    Article  CAS  Google Scholar 

  21. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.

    Article  CAS  Google Scholar 

  22. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431–5.

    Article  CAS  Google Scholar 

  23. Rozario R, Ramakrishna B. Histopathological study of chronic hepatitis B and C: a comparison of two scoring systems. J Hepatol. 2003;38:223–9.

    Article  Google Scholar 

  24. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614–8.

    Article  Google Scholar 

  25. Dorner T, Egerer K, Feist E, Burmester GR. Rheumatoid factor revisited. Curr Opin Rheumatol. 2004;16:246–53.

    Article  CAS  Google Scholar 

  26. Shmerling RH, Delbanco TL. The rheumatoid factor: an analysis of clinical utility. Am J Med. 1991;91:528–34.

    Article  CAS  Google Scholar 

  27. Wu JF, Wu TC, Chen CH, Ni YH, Chen HL, Hsu HY, et al. Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology. 2010;138:165–72.e1–3.

    Article  CAS  Google Scholar 

  28. Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology. 2015;61:1066–79.

    Article  Google Scholar 

  29. Pellicoro A, Ramachandran P, Iredale JP, Fallowfield JA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol. 2014;14:181–94.

    Article  CAS  Google Scholar 

  30. Sica A, Invernizzi P, Mantovani A. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology. 2014;59:2034–42.

    Article  Google Scholar 

  31. Cooper A, Tal G, Lider O, Shaul Y. Cytokine induction by the hepatitis B virus capsid in macrophages is facilitated by membrane heparan sulfate and involves TLR2. J Immunol. 2005;175:3165–76.

    Article  CAS  Google Scholar 

  32. Zhang JY, Zou ZS, Huang A, Zhang Z, Fu JL, Xu XS, et al. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B. PLoS One. 2011;6:e17484.

    Article  CAS  Google Scholar 

  33. Kazankov K, Barrera F, Moller HJ, Bibby BM, Vilstrup H, George J, et al. Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C. Hepatology. 2014;60:521–30.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, University of Health Sciences, Diskapı Yildirim Beyazit Training and Research Hospital, İrfan Baştuğ Cad. Dışkapı, Ankara, Turkey

    Yusuf Coskun M.D.

  2. Department of Gastroenterology, Ankara Yildirim Beyazit University, School of Medicine, Ankara, Turkey

    Ilhami Yuksel

Authors
  1. Yusuf Coskun M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilhami Yuksel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yusuf Coskun M.D..

Ethics declarations

Conflict of interest

Y. Coşkun and İ. Yüksel declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Coskun, Y., Yuksel, I. Serum rheumatoid factor is correlated with liver fibrosis in patients with chronic hepatitis B. Wien Klin Wochenschr 133, 432–440 (2021). https://doi.org/10.1007/s00508-020-01732-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-020-01732-8

Keywords

Search

Navigation