Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement

Rabbat, Joseph; Yang, Boyu; Lee, Hye Won; Lin, Huapeng; Tsochatzis, Emmanuel; Petta, Salvatore; Bugianesi, Elisabetta; Yoneda, Masato; Zheng, Ming-Hua; Hagstrom, Hannes; Boursier, Jerome; Calleja, Jose Luis; Goh, George Boon-Bee; Chan, Wah-Kheong; Gallego-Duran, Rocio; Sanyal, Arun J.; De Ledinghen, Victor; Newsome, Philip N.; Fan, Jian-Gao; Castera, Laurent; Lai, Michelle; Fournier-Poizat, Celine; Wong, Grace Lai-Hung; Zoncape, Mirko; Pennisi, Grazia; Armandi, Angelo; Nakajima, Atsushi; Liu, Wen-Yue; Shang, Ying; De Saint-Loup, Marc; Llop, Elba; Teh, Kevin Kim Jun; Lara-Romero, Carmen; Asgharpour, Amon; Mahgoub, Sara; Chan, Mandy Sau-Wai; Canivet, Clemence M.; Romero-Gomez, Manuel; Wong, Vincent Wai-Sun; Kim, Seung Up; Yip, Terry Cheuk-Fung

doi:10.3350/cmh.2025.0888

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Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement

Authors: Rabbat, Joseph ; Yang, Boyu ; Lee, Hye Won ; Lin, Huapeng ; Tsochatzis, Emmanuel ; Petta, Salvatore ; Bugianesi, Elisabetta ; Yoneda, Masato ; Zheng, Ming-Hua ; Hagstrom, Hannes ; Boursier, Jerome ; Calleja, Jose Luis ; Goh, George Boon-Bee ; Chan, Wah-Kheong ; Gallego-Duran, Rocio ; Sanyal, Arun J. ; De Ledinghen, Victor ; Newsome, Philip N. ; Fan, Jian-Gao ; Castera, Laurent ; Lai, Michelle ; Fournier-Poizat, Celine ; Wong, Grace Lai-Hung ; Zoncape, Mirko ; Pennisi, Grazia ; Armandi, Angelo ; Nakajima, Atsushi ; Liu, Wen-Yue ; Shang, Ying ; De Saint-Loup, Marc ; Llop, Elba ; Teh, Kevin Kim Jun ; Lara-Romero, Carmen ; Asgharpour, Amon ; Mahgoub, Sara ; Chan, Mandy Sau-Wai ; Canivet, Clemence M. ; Romero-Gomez, Manuel ; Wong, Vincent Wai-Sun ; Kim, Seung Up ; Yip, Terry Cheuk-Fung

Citation: CLINICAL AND MOLECULAR HEPATOLOGY, Vol.32(1) : 289-304, 2026-01

Journal Title: CLINICAL AND MOLECULAR HEPATOLOGY

ISSN: 2287-2728

Issue Date: 2026-01

MeSH: Adult ; Aged ; Biopsy ; Elasticity Imaging Techniques ; Fatty Liver* / complications ; Fatty Liver* / diagnosis ; Fatty Liver* / pathology ; Female ; Humans ; Liver Cirrhosis* / diagnosis ; Liver Cirrhosis* / pathology ; Liver Neoplasms ; Liver* / pathology ; Male ; Middle Aged ; Prognosis ; Severity of Illness Index

Keywords: Steatotic liver disease ; Metabolic dysfunction-associated steatotic liver disease ; Liver cirrhosis ; Liver fibrosis

Abstract: Background/Aims: Current guidelines recommend a 2-step approach for identifying advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), using Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE). However, some patients may exhibit discordant results. This study evaluates the histological severity and outcomes in patients with discordant FIB-4 and LSM results. Methods: This secondary analysis of the VCTE-Prognosis study included 12,950 patients evaluated for MASLD at 16 tertiary centers, of whom 2,915 underwent liver biopsy. Patients were categorized into four groups based on established FIB-4 (1.3) and LSM (8 kPa) cutoffs. Results: F3-F4 fibrosis was observed in 6.4%, 13.7%, 30.6%, and 62.4% in low-FIB-4-low-LSM (n=6,403), high-FIB-4-low-LSM (n=3,017), low-FIB-4-high-LSM (n=1,363), and high-FIB-4-high-LSM (n=2,167) groups, respectively. During a median follow-up of 47.4 months, 248 patients experienced hepatic decompensation, hepatocellular carcinoma, liver transplantation, or liver-related death. The incidence rates of liver-related events (LREs) were 0.67, 1.19, 2.58, and 21.30 per 1,000 person-years, respectively. Compared to low-FIB-4-low-LSM patients, those with low-FIB-4-high-LSM (adjusted subdistribution hazard ratio [aSHR] 4.12) and high-FIB-4-high-LSM (aSHR 21.38) had a significantly higher risk of LREs, while high-FIB-4-low-LSM patients did not. Similar findings were observed when hepatic decompensation and hepatocellular carcinoma were analyzed separately. Conclusions: Approximately 30% of patients in tertiary centers exhibit discordant FIB-4 and LSM results, with LSM more likely reflecting true severity. While some patients with discordant results may have advanced fibrosis, the overall incidence of LREs remains low. (Clin Mol Hepatol 2026;32:289-304)