Circulating fibroblast growth factor 21 and growth differentiation factor 15 are associated with severity of hepatic steatosis in people with HIV.

Background: Hepatic steatosis poses a significant health burden in people with HIV. Fibroblast growth factor 21 (FGF21) production from the liver regulates glucose metabolism. Higher serum levels of FGF21 are associated with hepatic steatosis and liver fibrosis in the general population. Growth differentiation factor 15 (GDF15) secretion from the liver is also upregulated in chronic inflammatory diseases and is associated with cardiovascular dysfunction in people with HIV. Here, we measured serum FGF21 and GDF15 concentrations in people with HIV and hepatic steatosis.

Methods: A total of 177 people with HIV with no other known cause of liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) quantification. Hepatic steatosis was defined as CAP ≥ 263 dB/m and advanced fibrosis as LSM > 12 kPa. Fasting serum total FGF21 and GDF15 concentrations were measured by ELISA. Relationships between biomarkers and hepatic parameters were analysed using a Censored Tobit Model.

Results: Participants with hepatic steatosis exhibited significantly higher mean (SD) levels of serum FGF21 (p = 0.002) and GDF15 (p = 0.02) than participants without steatosis. FGF21 levels increased with BMI (p = 0.04). Higher FGF21 and GDF15 levels correlated modestly with higher CAP (FGF21 r = 0.30, p < 0.001; GDF15 r = 0.21, p = 0.01) and LSM scores (FGF21 r = 0.25, p < 0.001; GDF15 r = 0.27, p = 0.01). FGF21 concentrations were 40% higher and GDF15 17% higher in persons with steatosis. Participants with the highest FGF21 levels (quartile 4) showed significantly higher mean CAP and LSM values, and longer mean duration of HIV compared with persons in quartile 1. Similar trends were also seen with GDF15 level quartiles.

Conclusions: People with HIV and hepatic steatosis had higher levels of serum FGF21 and GDF15 than those without steatosis, and levels correlated with disease severity. FGF21 and GDF15 may aid in identifying people with HIV at risk of steatotic liver disease.