Metabolic syndrome decouples insulin resistance from liver fibrosis in patients with Metabolic Associated Steatohepatitis

Abstract

Background The current study suggests that insulin resistance plays a significant role in liver fibrosis. However, animal studies imply a potential dissociation between liver fibrosis and insulin resistance. We aim to determine whether this dissociation exists in the human population and validate whether metabolic syndrome (MS) serves as an intermediary factor leading to this dissociation. Methods Data from NHANES 2017-March 2020 Pre-pandemic was employed in this study. The assessment of hepatic steatosis and fibrosis in participants was conducted using liver elastography, while the degree of insulin resistance was evaluated through the utilization of HOMA-IR from laboratory tests. Results The study revealed that the median age of participants was 55 years, with 1168 individuals diagnosed with Metabolic Associated Steatohepatitis (MASLD). Among these patients, 69% were identified as having Metabolic Syndrome (MS), while the remaining 31% did not. In the subset of MASLD patients without MS, logistic regression analysis showed no significant association between insulin resistance and either liver fibrosis or significant fibrosis. However, in MASLD patients with MS, individuals in the highest quartile of HOMA-IR had a respective 11.5(5.20, 25.6) and 13.0(4.96, 34.2) times higher risk of liver fibrosis or significant fibrosis compared to those in the lowest quartile of HOMA-IR. Conclusion In patients with MASLD, there is a dissociation between insulin resistance and liver fibrosis, and this dissociation is mediated by MS.