循环成纤维细胞生长因子21和生长分化因子15与HIV感染者肝脂肪变性的严重程度相关。

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

作者信息

Debroy Paula, Pike F, Gawrieh S, Corey K E, Hartig S, Balasubramanyam A, Ailstock K, Funderburg N, Lake J E

机构信息

Infectious Diseases, Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Gastroenterology, Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

出版信息

HIV Med. 2025 Jun 11. doi: 10.1111/hiv.70060.

DOI:10.1111/hiv.70060

PMID:40497366

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12229270/

Abstract

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.

摘要

背景

肝脂肪变性给HIV感染者带来了沉重的健康负担。肝脏产生的成纤维细胞生长因子21（FGF21）调节葡萄糖代谢。在普通人群中，较高的血清FGF21水平与肝脂肪变性和肝纤维化相关。肝脏分泌的生长分化因子15（GDF15）在慢性炎症性疾病中也上调，并且与HIV感染者的心血管功能障碍相关。在此，我们测量了HIV感染者和肝脂肪变性患者的血清FGF21和GDF15浓度。

方法

共有177例无其他已知肝脏疾病病因的HIV感染者接受了振动控制瞬时弹性成像检查，以量化受控衰减参数（CAP）和肝脏硬度测量（LSM）。肝脂肪变性定义为CAP≥263dB/m，重度纤维化定义为LSM>12kPa。采用酶联免疫吸附测定法（ELISA）测量空腹血清总FGF21和GDF15浓度。使用删失托比特模型分析生物标志物与肝脏参数之间的关系。

结果

与无脂肪变性的参与者相比，有肝脂肪变性的参与者血清FGF21（p=0.002）和GDF15（p=0.02）的平均（标准差）水平显著更高。FGF21水平随体重指数（BMI）升高而增加（p=0.04）。较高的FGF2和GDF15水平与较高的CAP（FGF21 r=0.30，p<0.001；GDF15 r=0.21，p=0.01）和LSM评分（FGF21 r=0.25，p<0.001；GDF15 r=0.27，p=0.01）适度相关。脂肪变性患者的FGF21浓度高40%，GDF15浓度高17%。FGF21水平最高的参与者（四分位数4）与四分位数1的参与者相比，平均CAP和LSM值显著更高，HIV平均病程更长。GDF15水平四分位数也呈现类似趋势。