Journal of Gastroenterology

, Volume 48, Issue 9, pp 1051–1060 | Cite as

Noninvasive scoring systems in patients with nonalcoholic fatty liver disease with normal alanine aminotransferase levels

  • Masato Yoneda
  • Kento Imajo
  • Yuichiro EguchiEmail author
  • Hideki Fujii
  • Yoshio Sumida
  • Hideyuki Hyogo
  • Masafumi Ono
  • Yasuaki Suzuki
  • Takumi Kawaguchi
  • Noriaki Aoki
  • Michio Sata
  • Kazuyuki Kanemasa
  • Yutaka Kohgo
  • Toshiji Saibara
  • Kazuaki Chayama
  • Yoshito Itoh
  • Toshikazu Yoshikawa
  • Keizo Anzai
  • Kazuma Fujimoto
  • Takeshi Okanoue
  • Atsushi Nakajima
  • Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)
Original Article—Liver, Pancreas, and Biliary Tract



The severity of liver fibrosis must be estimated to determine the prognosis, for surveillance, and for optimal treatment of nonalcoholic fatty liver disease (NAFLD). However, the severity of hepatic fibrosis tends to be underestimated in patients with normal ALT.


We investigated histological data and scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) of 1,102 liver-biopsy-confirmed NAFLD patients.


A total of 235 NAFLD patients with normal ALT were estimated to exist. The ratio of advanced fibrosis (stage 3–4) was seen in 16.1 % of subjects with normal ALT. Scoring systems, especially the FIB-4 index and NAFLD fibrosis score, were clinically very useful (AUROC >0.8), even in patients with normal ALT. Furthermore, with resetting of the cutoff values, the FIB-4 index (>1.659) and NAFLD fibrosis score (>0.735) were found to have a higher sensitivity and higher specificity for the prediction of advanced fibrosis, and all of these scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) had higher negative predictive values (>90.3 %). By using the resetting cutoff value, liver biopsy could have been avoided in 60.4 % (FIB-4), 66.4 % (NAFLD fibrosis score), 51.9 % (BARD score), and 62.1 % (AST/ALT ratio).


We reset the cutoff values of numerous non-invasive scoring systems to improve their clinical usefulness in the prediction of liver fibrosis in NAFLD patients with normal ALT, and these non-invasive scoring systems with the reset cutoff values could be of substantial benefit to reduce the number of liver biopsies performed.


NAFLD NASH Normal ALT Scoring systems 



Nonalcoholic fatty liver disease


Nonalcoholic steatohepatitis


Aspartate aminotransferase


Alanine aminotransferase


Area under the receiver-operating characteristic curve


Body mass index


Low-density lipoprotein


High-density lipoprotein


Negative predictive value


Positive predictive value


AST/ALT ratio



This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (22790660 to MY and 22590741 to YE), by a Grant from the Chiyoda Mutual Life Foundation to YS, and by a Thrust Area Research Grand from Osaka City University to HF and NK.

Conflict of interest

The authors have no conflicts of interest to disclose.


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Copyright information

© Springer Japan 2012

Authors and Affiliations

  • Masato Yoneda
    • 1
  • Kento Imajo
    • 1
  • Yuichiro Eguchi
    • 2
    Email author
  • Hideki Fujii
    • 3
  • Yoshio Sumida
    • 4
  • Hideyuki Hyogo
    • 5
  • Masafumi Ono
    • 6
  • Yasuaki Suzuki
    • 7
  • Takumi Kawaguchi
    • 8
  • Noriaki Aoki
    • 9
  • Michio Sata
    • 8
  • Kazuyuki Kanemasa
    • 10
  • Yutaka Kohgo
    • 7
  • Toshiji Saibara
    • 6
  • Kazuaki Chayama
    • 5
  • Yoshito Itoh
    • 4
  • Toshikazu Yoshikawa
    • 4
  • Keizo Anzai
    • 2
  • Kazuma Fujimoto
    • 2
  • Takeshi Okanoue
    • 11
  • Atsushi Nakajima
    • 1
  • Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)
  1. 1.Division of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
  2. 2.Division of HepatologySaga Medical SchoolSagaJapan
  3. 3.Department of HepatologyGraduate School of Medicine Osaka City UniversityOsakaJapan
  4. 4.Department of Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  5. 5.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  6. 6.Department of Gastroenterology and HepatologyKochi Medical SchoolKochiJapan
  7. 7.Division of Gastroenterology and Hematology/Oncology, Department of MedicineAsahikawa Medical CollegeAsahikawaJapan
  8. 8.Department of Medicine and Digestive Disease Information and ResearchKurume University School of MedicineKurumeJapan
  9. 9.School of Biomedical InformaticsUniversity of Texas Health Science Center at HoustonHoustonUSA
  10. 10.Center for Digestive and Liver DiseasesNara City HospitalNaraJapan
  11. 11.Hepatology CenterSaiseikai Suita HospitalSuitaJapan

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