Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

Mohamed Mahmoud Marey; Mohamed Belal; Abdelaziz A Awad; Eslam Mohammed Rabea; Malak A Hassan; Ahmed W Abbas; Abdulqadir J Nashwan

doi:10.1016/j.clinre.2024.102357

Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

Clin Res Hepatol Gastroenterol. 2024 Apr 28;48(6):102357. doi: 10.1016/j.clinre.2024.102357. Online ahead of print.

Authors

Mohamed Mahmoud Marey¹, Mohamed Belal¹, Abdelaziz A Awad², Eslam Mohammed Rabea¹, Malak A Hassan³, Ahmed W Abbas⁴, Abdulqadir J Nashwan⁵

Affiliations

¹ Faculty of Medicine, Alexandria University, Alexandria, Egypt; Medical Research Group of Egypt (MRGE), Cairo, Egypt.
² Medical Research Group of Egypt (MRGE), Cairo, Egypt; Faculty of Medicine, Azhar University, Cairo, Egypt.
³ Faculty of Medicine, Alexandria University, Alexandria, Egypt.
⁴ Medical Research Group of Egypt (MRGE), Cairo, Egypt; Faculty of Medicine, Mansoura University, Egypt.
⁵ Department of Nursing, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Doha, Qatar; Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar. Electronic address: anashwan@hamad.qa.

PMID: 38688423
DOI: 10.1016/j.clinre.2024.102357

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of NASH. We aimed to investigate the efficacy and safety of aldafermin in patients with NASH.

Methods: PubMed, Scopus, Cochrane Library, and Web of Science were searched till November 2023 to identify eligible randomized controlled trials (RCTs). Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses (1 mg and 3 mg) of aldafermin.

Results: Four RCTs with a total of 491 patients were included. Aldafermin showed a dose-dependent improvement in the ≥30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: -19.79, 95 % CI [-30.28 to -9.3]) and (MD: -21.91, 95 % CI [-29.62 to -14.21]), aspartate aminotransferase levels (MD: -11.79, 95 % CI [-18.06 to -5.51]) and (MD: -13.9, 95 % CI [-18.59 to -9.21]), and enhanced liver fibrosis score (ELF) (MD: -0.13, 95 % CI [-0.29 to 0.02]) and (MD: -0.33, 95 % CI [-0.50 to -0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup.

Conclusion: Aldafermin is a promising well-tolerated therapeutic agent for NASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer NASH trials are warranted to enhance the robustness of the evidence.

Keywords: Aldafermin; FGF19; Fatty liver; NAFLD; NASH.

Publication types

Review