# Higher afamin concentrations are associated with higher fatty liver indices: Population‐based KORA F4/FF4 study

## TL;DR

Higher levels of afamin are linked to more severe fatty liver disease, especially in men and those with prediabetes or diabetes.

## Contribution

This study identifies afamin as a potential new biomarker for non-invasive diagnosis of fatty liver disease.

## Key findings

- Higher afamin levels are associated with increased fatty liver indicators like NAFLD LFS and fatty liver index.
- The association between afamin and fatty liver is stronger in men and individuals with prediabetes or diabetes.
- Afamin levels predict future increases in NAFLD LFS over a 6.5-year follow-up.

## Abstract

Previous studies suggest that afamin is associated with steatotic liver diseases (SLD). However, the exact role of afamin in SLD development and fibrogenesis remains unclear. Potential modifying effects of sex and glucose tolerance status have also not been examined. Therefore, we investigated the associations of afamin with steatotic liver diseases and fibrosis defined by non‐invasive tests and assessed for possible effect modifications.

This study included 3080 participants from the population‐based KORA F4/FF4 cohort. Cross‐sectional and prospective associations (follow‐up time 6.5 years) between afamin and NAFLD liver fat score (NAFLD LFS), hepatic steatosis index, fatty liver index and the fibrosis‐4 index were assessed using multiple linear regression models. Models were adjusted for age, sex, body mass index, smoking status, alcohol consumption, physical activity, metabolic parameters, medication and subclinical inflammation.

In the cross‐sectional analysis, afamin concentrations were positively associated with NAFLD LFS (β = .32; 95% CI .27–.37), hepatic steatosis index (β = .33; 95% CI .26–.39) and fatty liver index (β = 1.78; 95% CI 1.47–2.08) (all p < .001), but not with fibrosis‐4 index. In the prospective analysis, higher afamin levels were associated with a higher increase only in NAFLD LFS (p < .001). Cross‐sectional and prospective associations between afamin and NAFLD LFS were more pronounced in men than in women (p
interaction < .001 and .022; respectively). Cross‐sectional associations between afamin and NAFLD LFS were also stronger in individuals with prediabetes or diabetes compared to those with normal glucose tolerance (p
interaction < .001).

Higher afamin concentrations are positively associated with NAFLD LFS with potential effect modification by sex and glucose tolerance status.

The present study aimed to investigate the associations between afamin and fatty liver and fibrosis indices and to study potential modifying effects of sex and glucose tolerance status on these associations in individuals from the population‐based KORA F4/FF4 cohort. Higher afamin concentrations were positively associated with NAFLD LFS in both cross‐sectional and prospective analyses, with potential effect modification by sex and glucose tolerance status. These findings suggest that afamin may be a novel biomarker for the non‐invasive diagnosis of MASLD.