Diagnostic accuracy of the Fibrosis-4 index for advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease with type 2 diabetes: A systematic review and meta-analysis

Han, Ji Won; Kim, Hee Yeon; Yu, Jung Hwan; Kim, Mi Na; Chon, Young Eun; An, Ji Hyun; Jin, Young-Joo; Choi, Miyoung; Kim, Seung Up; Lee, Han Ah; Jun, Dae Won

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Original Article

Diagnostic accuracy of the Fibrosis-4 index for advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease with type 2 diabetes: A systematic review and meta-analysis

Ji Won Han^1,2, Hee Yeon Kim^1,3, Jung Hwan Yu⁴, Mi Na Kim⁵, Young Eun Chon⁶, Ji Hyun An⁷, Young-Joo Jin⁴, Miyoung Choi⁸, Seung Up Kim⁴, Han Ah Lee⁹, Dae Won Jun¹⁰

¹The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Korea
²Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic Korea
³Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Bucheon, Republic Korea
⁴Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic Korea
⁵Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic Korea
⁶Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Republic Korea
⁷Department of Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Republic Korea
⁸Clinical Evidence Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Republic Korea
⁹Department of Internal Medicine, College of Medicine, Chung-Ang University Hospital, Seoul, Republic Korea
¹⁰Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic Korea

Correspondence :

Han Ah Lee ,
Email: amelia86@naver.com
Dae Won Jun ,
Email: gongori1004@gmail.com

Received: May 4, 2024 Revised: July 23, 2024 Accepted: July 23, 2024
*Ji Won Han and Hee Yeon Kim contributed equally to this work.

ABSTRACT

Background/Aims
The Fibrosis-4 index (FIB-4) is a non-invasive test widely used to rule out advanced liver fibrosis (AF) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its diagnostic accuracy in MASLD patients with type 2 diabetes mellitus (T2DM) are controversial due to the high prevalence of AF in this population.
Methods
Research focusing on the diagnostic accuracy of FIB-4 for liver fibrosis as validated by liver histology in MASLD patients with T2DM was included, and 12 studies (n=5,624) were finally included in the meta-analysis. Sensitivity, specificity, hierarchical summary receiver operating characteristic (HSROC), positive predictive values (PPVs), and negative predictive values (NPVs) at low cutoffs (1.3–1.67) and high cutoffs (2.67–3.25) for ruling in and out AF, were calculated.
Results
At low cutoffs, the meta-analysis revealed a sensitivity of 0.74, specificity of 0.62, and HSROC of 0.75. At high cutoffs, the analysis showed a sensitivity of 0.33, specificity of 0.92, and HSROC of 0.85, suggesting FIB-4 as useful for identifying or excluding AF. In subgroup analyses, high mean age and F3 prevalence were associated with lower sensitivity. The calculated NPV and PPV were 0.82 and 0.49 at low cutoffs, whereas the NPV was 0.28 and the PPV was 0.70 at high cutoffs. There were insufficient estimated NPVs <0.90 at a hypothesized prevalence of AF >30% at an FIB-4 cutoff range of 1.3–1.67.
Conclusions
Collectively, FIB-4 has moderate diagnostic accuracy for identifying or excluding AF in MASLD patients with T2DM, but more evidence must be accumulated due to the limited number of currently reported studies and their heterogeneity.