Clinical and Molecular Hepatology

"FIB-4"

Letter to the Editor

Discordant FIB-4 and liver stiffness in metabolic dysfunction-associated steatotic liver disease: Toward clinically coherent risk stratification: Letter to the Editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”: Zhanna Zhang, Zichen Yu, Gongqiang Wu; Clin Mol Hepatol 2026;32(3):e297-e299.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0049

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Correspondence

Correspondence to letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”: Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Seung Up Kim; Clin Mol Hepatol 2026;32(3):e419-e421.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0073

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Letters to the Editor

Clinical implications of discordant FIB-4 and LSM in MASLD: Integrating evidence and optimizing pathways: Letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”: Deliang Huang, Jun Chen; Clin Mol Hepatol 2026;32(3):e294-e296.
Published online January 20, 2026; DOI: https://doi.org/10.3350/cmh.2026.0027

Citations

Citations to this article as recorded by

Correspondence to letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”
Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(3): e419. CrossRef

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Crossref

Letter to the editor on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”: Chunyan Wang, Jun Sun, Yinyan Li; Clin Mol Hepatol 2026;32(2):e146-e148.
Published online June 9, 2025; DOI: https://doi.org/10.3350/cmh.2025.0539

Citations

Citations to this article as recorded by

Correspondence to letter to the editor on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
Hye Won Lee, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(2): e244. CrossRef

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Editorial

Viral hepatitis

Metabolic dysfunction in patients following DAA-induced viral cure for HCV infection: A non-negligible risk to liver-related health: Editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”: Chen-Hua Liu, Yu-Ping Chang; Clin Mol Hepatol 2025;31(2):658-661.
Published online February 17, 2025; DOI: https://doi.org/10.3350/cmh.2025.0155

Citations

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Longitudinal Changes in Lipid Profile After Sustained Virological Response in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals
Oana Koppandi, Bogdan Miutescu, Iulia Ratiu, Alexandru Popa, Camelia Nica, Eyad Gadour, Bogdan Dan Totolici, Raluca Lupusoru, Ana Maria Ghiuchici, Eftimie Miutescu
Healthcare.2026; 14(4): 486. CrossRef
Microbial exposure and host responses to infection reshape the disease trajectory of MASLD
Yunqi Zhang, Qingqing Xun, Shuyu Liu, Bo Zhuang, Meiyue Zang, Chengwei Tan, Yu Cui, Ruiji Li, Qianqian Zhang
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
Correspondence to editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”
Tom Ryu, Young Chang, Seung Up Kim, Jae Young Jang
Clinical and Molecular Hepatology.2025; 31(2): e203. CrossRef
Reply to correspondence on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”
Chen-Hua Liu, Yu-Ping Chang
Clinical and Molecular Hepatology.2025; 31(2): e232. CrossRef
Viral oncogenesis and immune remodeling: Decoding the therapeutic potential of immune checkpoint inhibitors in virus-associated cancers
Lihua Qi, Bai Hu, Canhui Cao, Ting Peng, Miaochun Xu, Shiyi Liu, Yashi Xu, Xiaojie Liu, Wencheng Ding, Li Li, Shitong Lin
Biomedicine & Pharmacotherapy.2025; 191: 118515. CrossRef

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Letter to the Editor

Steatotic liver disease

The fibrosis-4 index for advanced liver fibrosis in NAFLD with T2DM: Half a loaf is better than no bread: Zeyu Wang, Dong Wan, Meidong Xu, Yong Jiang; Clin Mol Hepatol 2025;31(1):e25-e26.
Published online December 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0993

Citations

Citations to this article as recorded by

Age serves as the silent architect of FIB-4’s precision in unveiling advanced hepatic fibrosis in MASLD with T2DM: Correspondence to letter to the editor on “Diagnostic accuracy of the fibrosis-4 index for advanced liver fibrosis in nonalcoholic fatty liv
Ji Won Han, Dae Won Jun
Clinical and Molecular Hepatology.2025; 31(2): e152. CrossRef

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Original Articles

Steatotic liver disease

Diagnostic accuracy of the Fibrosis-4 index for advanced liver fibrosis in nonalcoholic fatty liver disease with type 2 diabetes: A systematic review and meta-analysis: Ji Won Han, Hee Yeon Kim, Jung Hwan Yu, Mi Na Kim, Young Eun Chon, Ji Hyun An, Young-Joo Jin, Miyoung Choi, Seung Up Kim, Han Ah Lee, Dae Won Jun; Clin Mol Hepatol 2024;30(Suppl):S147-S158.
Published online July 25, 2024; DOI: https://doi.org/10.3350/cmh.2024.0330

Background/Aims
The Fibrosis-4 index (FIB-4) is a noninvasive test widely used to rule out advanced liver fibrosis (AF) in patients with nonalcoholic fatty liver disease (NAFLD). However, its diagnostic accuracy in NAFLD patients with type 2 diabetes mellitus (T2DM) is 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 NAFLD 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 NAFLD patients with T2DM, but more evidence must be accumulated due to the limited number of currently reported studies and their heterogeneity.

Citations

Citations to this article as recorded by

Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes
Yuping Chen, Bingtian Dong, Xinrui Jin, Chuan Liu, Ming-Hua Zheng, Xiao Liang, Yameng Sun, Hye Won Lee, Huapeng Lin, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Hannes Hagström, Jérôme Boursier, José Luis Calleja, George Boo
Gut.2026; 75(3): 576. CrossRef
Part 2: CAR Metabolic Dysfunction-Associated Steatotic Liver Disease Working Group Recommendations for Risk Stratifying Patients With MASLD
Mitchell P. Wilson, Gavin Low, Abdel-Aziz Shaheen, Andreu F. Costa, An Tang, Emily Pang, Silvia Chang, Alexandra Medellin, Jérémy Dana, Noam Millo, Ania Kielar, Li Xin Zhang, Toni Whitaker, Mark Swain, Victoria Leung, Daisy Fung, Casey Hurrell, Christophe
Canadian Association of Radiologists Journal.2026; 77(1): 73. CrossRef
Prognostic value of the FIB-4 index in patients with myocardial infarction with non-obstructive coronary arteries
Wei Zhang, Yuqi Chen, Liu Zhu, Siliang Peng, Mengchao Jin, Jiayu Yin
International Journal of Cardiology.2026; 445: 134045. CrossRef
MRI Proton Density Fat Fraction From PET/MRI Elucidates the Biphasic Impact of Hepatic Steatosis on Liver 18F-FDG Uptake
Zhaoting Meng, Mu Lin, TungChin Chu, Dandan Zhu, Liling Peng, Mingxiang Sun, Sisi Peng, Gang Feng, Xin Gao
Journal of Computer Assisted Tomography.2026; 50(4): 534. CrossRef
Cell-free DNA fragmentomes for noninvasive detection of liver cirrhosis and other diseases
Akshaya V. Annapragada, Zachariah H. Foda, Hope Orjuela, Carter Norton, Shashikant Koul, Noushin Niknafs, Sarah Short, Keerti Boyapati, Adrianna Bartolomucci, Dimitrios Mathios, Michael Noë, Chris Cherry, Jacob Carey, Alessandro Leal, Bryan Chesnick, Nich
Science Translational Medicine.2026;[Epub] CrossRef
Metabolic Dysfunction‐Associated Steatotic Liver Disease and Obesity: Pathogenesis, Diagnostics, Risk Stratification, and Therapeutic Approach
Beom Kyung Kim
The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef
Metabolic dysfunction–associated steatotic liver disease in Cushing’s syndrome: prevalence, determinants, and changes after remission
Enes Ucgul, Burak Menekse, Revah Cankaya, Murat Bugra Gorgulu, Bekir Ucan, Erman Cakal, Muhammed Kizilgul
Frontiers in Endocrinology.2026;[Epub] CrossRef
Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial
Małgorzata Moszak, Mariusz Kaczmarczyk, Matylda Kręgielska-Narożna, Igor Łoniewski, Karolina Skonieczna-Żydecka, Monika Szulińska, Paweł Bogdański
Nutrition.2026; 151: 113325. CrossRef
Estimation of liver fibrosis and cirrhosis risk using non-invasive biomarkers in people living with HIV and prediabetes in Tanzania
Jeffrey V. Lazarus, Trenton M. White, Kaushik Ramaiya, Sokoine Kivuyo, Sayoki Mfinanga, Erik van Widenfelt, Paul N. Brennan, Camila A. Picchio, Hannes Hagström, Rickard Strandberg, Anupam Garrib
Metabolism and Target Organ Damage.2026;[Epub] CrossRef
The risk of cardiovascular events in metabolic dysfunction–associated steatotic liver disease according to fibrosis stage and diabetes status: A cohort study
Jaehong Jeong, Jung Pyo Hong, Dong Yun Kim, Jae Seung Lee, Mi Na Kim, Jeong Eun Song, Hyun Chin Cho, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Hye Won Lee, Seung Up Kim
Hepatology Communications.2026;[Epub] CrossRef
Large‐Scale Plasma Proteomics Enhances Prediction of Liver‐Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank
Chenhao Ye, Ziqi Zhang, Yi Ding, You Yu, Shengan Zhang, Jiashu Pan, Shuchang Nie, Sumei Li, Li Zhang, Lili Lu, Lei Wang, Guang Ji
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Risk of HCC in Elderly Patients With MASLD: Proposal of an Effective Surveillance Strategy
Young Eun Chon, Kyung‐Do Han, Ju Dong Yang, Ju‐Yeong Park, Hyun‐Seok Kim, Hyung Woong Lee, Tae Seop Lim, Beom Kyung Kim
Journal of Gastroenterology and Hepatology.2026; 41(9): 2913. CrossRef
Associations between adiposity indices and liver steatosis and stiffness assessed by two-dimensional shear wave elastography in patients with type 2 diabetes mellitus: a cross-sectional study
Asieh Mansour, Mehrnam Amouei, Amir Hossein Esmaeili, Atie Sadat Khorasanian, Hadis Gerami, Amir Reza Radmard, Arina Afshinpour, Fateme Sadat Fani Sadrabadi, Elham Madreseh, Mohammad Reza Mohajeri-Tehrani, Sayed Mahmoud Sajjadi-Jazi
BMC Endocrine Disorders.2026;[Epub] CrossRef
Lipid Profiles in Liver Steatosis and Liver Fibrosis in Patients with Type 2 Diabetes and Coronary Artery Disease
Laura A. M. Konings, Weiwei Xu, Vivian D. de Jong, Marco Alings, Jean-Claude Tardif, Abraham M. Lincoff, Gregory G. Schwartz, Diederick E. Grobbee, Manuel Castro Cabezas
Diabetology.2026; 7(9): 162. CrossRef
Reply to: “A machine learning model to predict liver-related outcomes after the functional cure of chronic hepatitis B: Is cirrhosis driving the performance?”
Moon Haeng Hur, Jeong-Hoon Lee
Journal of Hepatology.2025; 82(3): e143. CrossRef
The fibrosis-4 index for advanced liver fibrosis in NAFLD with T2DM: Half a loaf is better than no bread
Zeyu Wang, Dong Wan, Meidong Xu, Yong Jiang
Clinical and Molecular Hepatology.2025; 31(1): e25. CrossRef
Non-Invasive Liver Fibrosis Test Using Shear Wave Elastography
Ji Won Han
The Korean Journal of Medicine.2025; 100(1): 26. CrossRef
Age serves as the silent architect of FIB-4’s precision in unveiling advanced hepatic fibrosis in MASLD with T2DM: Correspondence to letter to the editor on “Diagnostic accuracy of the fibrosis-4 index for advanced liver fibrosis in nonalcoholic fatty liv
Ji Won Han, Dae Won Jun
Clinical and Molecular Hepatology.2025; 31(2): e152. CrossRef
Targeting endoplasmic reticulum proteostasis in liver fibrosis: From signaling mechanisms to therapeutic opportunities
Yawei Kong, Zhengyang Chen, Zhentian Nie, Wei Chen
Pharmacological Research.2025; 217: 107823. CrossRef
Comparison of FIB-4, APRI and AST/ALT ratio with FibroScan in patients with NAFLD and type 2 diabetes: a single-center study from Bangladesh
Muhammad Shah Alam, Syeda Tanzina Kalam, Monirul Islam Khan, Jabed Ahmed, Rahul Saha, A. B. M. Kamrul-Hasan
Egyptian Liver Journal.2025;[Epub] CrossRef
Impact of a high dietary fiber cereal meal intervention on the progression of liver fibrosis in T2DM with MASLD
Xi-Shuang Chen, Hui-Zhen Liu, Fang Huang, Jian Meng, Jing-Xian Fang, Yu Han, Hui-Ming Zou, Qing Gu, Xue Hu, Qian-Wen Ma, Yue-Xia Han, Sui-Jun Wang
Frontiers in Endocrinology.2025;[Epub] CrossRef
Association between fibrosis-4 index and coronary heart disease: a population-based study
Pan Jia, Mamajan Annamyradova, Genhao Fan, Qizhen Zhang, Yankun Song, Qiaozhi Li, Minghao Liu, Zuoying Xing, Yongxia Wang
BMC Cardiovascular Disorders.2025;[Epub] CrossRef
Forns index and fatty liver index, but not FIB-4, are associated with indices of glycaemia, pre-diabetes and type 2 diabetes: analysis of The Maastricht Study
Leen Heyens, Hanna Kenjic, Pieter Dagnelie, Casper Schalkwijk, Coen Stehouwer, Steven Meex, Jeroen Kooman, Otto Bekers, Marleen van Greevenbroek, Hans Savelberg, Geert Robaeys, Bastiaan de Galan, Annemarie Koster, Martien van Dongen, Simone Eussen, Ger Ko
BMJ Open Gastroenterology.2024; 11(1): e001466. CrossRef

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Steatotic liver disease

Elevated red cell distribution width is associated with advanced fibrosis in NAFLD: Hwa Mok Kim, Bum Soo Kim, Yong Kyun Cho, Byung Ik Kim, Chong Il Sohn, Woo Kyu Jeon, Hong Joo Kim, Dong Il Park, Jung Ho Park, Kwan Joong Joo, Chang Joon Kim, Yong Sung Kim, Woon Je Heo, Won Seok Choi; Clin Mol Hepatol 2013;19(3):258-265.
Published online September 30, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.3.258

Abstract
PDF

Background/Aims

The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores.

Methods

This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively.

Results

After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and ≥2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of ≥1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score.

Conclusions

Elevated RDW is independently associated with advanced fibrosis in NAFLD.

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