Is metabolic‐dysfunction‐associated fatty liver disease or advanced liver fibrosis associated with erythropoietin stimulating agent hypo‐responsiveness among patients with end‐stage kidney disease on haemodialysis?

• Published in: Nephrology (Carlton, Vic.) Vic.), 2023-08, Vol.28 (8), p.425-433
• Main Authors: Wong, Wei‐Kei, Chan, Wah‐Kheong, Ganapathy, Shubash, Lim, Soo‐Kun
• Format: Article
• Language: English
• Subjects: advanced liver fibrosis; Anemia; Cholesterol; Cross-Sectional Studies; Erythropoietin; Erythropoietin - adverse effects; Fatty liver; Female; Fibrosis; haemodialysis; Hemodialysis; Humans; Kidney diseases; Kidney Failure, Chronic - complications; Liver Cirrhosis - complications; Liver Cirrhosis - diagnosis; Liver diseases; metabolic‐dysfunction‐associated fatty liver disease; Metabolism; Multivariate analysis; Renal Dialysis - adverse effects; resistance
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/nep.14186

Aim This study aims to determine if metabolic‐dysfunction‐associated fatty liver disease (MAFLD) or advanced liver fibrosis is associated with erythropoietin stimulating agent (ESA) hypo‐responsiveness in hemodialysis patients. Methods In a cross‐sectional study of 379 hemodialysis patients, FibroTouch transient elastography was performed on all patients. Erythropoeitin resistance index (ERI) was used to measure the responsiveness to ESA. Patients in the highest tertile of ERI were considered as having ESA hypo‐responsiveness. Results The percentage of patients with ESA hypo‐responsiveness who had MAFLD was lower than patients without ESA hypo‐responsiveness. FIB‐4 index was significantly higher in ESA hypo‐responsive patients. In multivariate analysis, female gender (aOR = 3.4, 95% CI = 1.9–6.2, p < 0.001), dialysis duration ≥50 months (aOR = 1.8, 95% CI = 1.1–2.9, p < 0.05), elevated waist circumference (aOR = 0.4, 95% CI = 0.2–0.8, p = 0.005), low platelet (aOR = 2.6, 95% CI 1.3–5.1, p < 0.01), elevated total cholesterol (aOR = 0.5, 95% CI 0.3–0.9, p < 0.05) and low serum iron (aOR = 3.8, 95% CI = 2.3–6.5, p < 0.001) were found to be independent factors associated with ESA hypo–responsiveness. Neither MAFLD nor advanced liver fibrosis was independently associated with ESA hypo–responsiveness. However, every 1 kPA increase in LSM increased the chance of ESA–hyporesponsiveness by 13% (aOR = 1.1, 95% CI =  1.0–1.2, p = 0.002) when UAP and LSM were used instead of presence of MAFLD and advanced liver fibrosis, respectively. Conclusion MAFLD and advanced liver fibrosis were not independently associated with ESA hypo‐responsiveness. Nevertheless, higher FIB‐4 score in ESA hypo‐responsive group and significant association between LSM and ESA hypo‐responsiveness suggest that liver fibrosis may be a potential clinical marker of ESA hypo‐responsiveness. Summary at a Glance A cross‐sectional study of 379 haemodialysis patients in Malaysia showed no significant association between metabolic‐dysfunction‐associated fatty liver disease or advanced liver fibrosis with erythropoietin stimulating agent (ESA) hypo‐responsiveness. However, liver fibrosis may be a potential clinical marker of ESA hypo‐responsiveness given higher FIB‐4 score in ESA hypo‐responsive group and significant association between liver stiffness measurement and ESA hypo‐responsiveness.