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

Clin Mol Hepatol. 2026 Jan;32(1):289-304. doi: 10.3350/cmh.2025.0888. Epub 2025 Nov 11.

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.

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

Publication types

  • Multicenter Study

MeSH terms

  • 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