Validation of the fibrosis-4 (FIB-4) index in the diagnosis of liver disease of rheumatoid arthritis patients treated with methotrexate

Abstract

Objectives: To validate the usefulness of a hepatic fibrosis scoring system fibrosis-4 (FIB-4) index to diagnose liver diseases in rheumatoid arthritis (RA) patients treated with methotrexate (MTX).

Methods: The FIB-4 index (age(years) × AST(U/L)/platelet (PLT) (10⁹/L) × √ALT(U/L)), proposed as a predictor for liver fibrosis in HIV/HCV coinfection, was evaluated in this study. RA patients on MTX treatment were screened by FIB-4 index values to detect fibrotic change in the liver. Liver biopsy specimens were examined histologically in patients with high values.

Results: Thirteen of 14 patients showed histology closely resembling non-alcoholic steatohepatitis. In three of them, two biopsies were performed: 1st, during MTX treatment; and 2nd, after discontinuation of MTX. All of them showed improvement in histology along with decreased FIB-4 values. Age, AST/√ALT, and 1/PLT, as well as creatinine levels and cumulative MTX doses were significantly higher in the high FIB-4 group compared with the low FIB-4 group. In the high FIB-4 group, 1/PLT and AST/√ALT were significantly correlated with FIB-4 values, but age was not.

Conclusions: The FIB-4 index is simple to calculate and a valuable marker to diagnose liver disease in RA patients treated with long-term MTX administration.

Keywords:

• Fibrosis-4 index
• folate
• methotrexate
• non-alcoholic steatohepatitis
• rheumatoid arthritis

Acknowledgements

The authors would like to express our sincere gratitude to Dr. H. Hashimoto for his excellent advice on the metabolism of the folate cycle and the remethylation cycle. The authors would like to express our sincere gratitude to M. Hayashi for this great help in statistical analysis. The authors would also like to thank Ms. Miwa Saito, Mr. Yuhei Nikaido and Mr. Kenji Nozaki for preparing this manuscript.

Disclosure statement

None.