Open Access Open Badges Research article

Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population

Yoshio Sumida1, Masato Yoneda2, Hideyuki Hyogo3, Yoshito Itoh4, Masafumi Ono5*, Hideki Fujii6, Yuichiro Eguchi7, Yasuaki Suzuki8, Noriaki Aoki9, Kazuyuki Kanemasa1, Koji Fujita2, Kazuaki Chayama3, Toshiji Saibara5, Norifumi Kawada6, Kazuma Fujimoto7, Yutaka Kohgo8, Toshikazu Yoshikawa4, Takeshi Okanoue10 and Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

Author Affiliations

1 Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan

2 Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

3 Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

4 Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

5 Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan

6 Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

7 Department of Internal Medicine, Saga Medical School, Saga University, Saga, Japan

8 Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan

9 School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, USA

10 Hepatology Center, Saiseikai Suita Hospital, Suita, Japan

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BMC Gastroenterology 2012, 12:2  doi:10.1186/1471-230X-12-2

Published: 5 January 2012



A reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD.


The areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (109/L) × √ALT (IU/L))


Advanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies.


The FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.