Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials
<h3>Background</h3><p dir="ltr">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. A...
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2024
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| _version_ | 1864513515920818176 |
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| author | Mohamed Mahmoud Marey (18560902) |
| author2 | Mohamed Belal (18560905) Abdelaziz A. Awad (18560908) Eslam Mohammed Rabea (18560911) Malak A. Hassan (18560914) Ahmed W. Abbas (18560917) Abdulqadir J. Nashwan (11659453) |
| author2_role | author author author author author author |
| author_facet | Mohamed Mahmoud Marey (18560902) Mohamed Belal (18560905) Abdelaziz A. Awad (18560908) Eslam Mohammed Rabea (18560911) Malak A. Hassan (18560914) Ahmed W. Abbas (18560917) Abdulqadir J. Nashwan (11659453) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohamed Mahmoud Marey (18560902) Mohamed Belal (18560905) Abdelaziz A. Awad (18560908) Eslam Mohammed Rabea (18560911) Malak A. Hassan (18560914) Ahmed W. Abbas (18560917) Abdulqadir J. Nashwan (11659453) |
| dc.date.none.fl_str_mv | 2024-06-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.clinre.2024.102357 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Efficacy_and_safety_of_aldafermin_in_non-alcoholic_steatohepatitis_A_systematic_review_and_meta-analysis_of_randomized_controlled_trials/25827250 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences NAFLD NASH Fatty liver Aldafermin FGF19 |
| dc.title.none.fl_str_mv | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">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.</p><p><br></p><h3>Methods</h3><p dir="ltr">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.</p><p><br></p><h3>Results</h3><p dir="ltr">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.</p><p><br></p><h3>Conclusion</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Clinics and Research in Hepatology and Gastroenterology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.clinre.2024.102357" target="_blank">https://dx.doi.org/10.1016/j.clinre.2024.102357</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_5fad3b69adff78d26d8b089f372b6585 |
| identifier_str_mv | 10.1016/j.clinre.2024.102357 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25827250 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trialsMohamed Mahmoud Marey (18560902)Mohamed Belal (18560905)Abdelaziz A. Awad (18560908)Eslam Mohammed Rabea (18560911)Malak A. Hassan (18560914)Ahmed W. Abbas (18560917)Abdulqadir J. Nashwan (11659453)Biomedical and clinical sciencesClinical sciencesNAFLDNASHFatty liverAldaferminFGF19<h3>Background</h3><p dir="ltr">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.</p><p><br></p><h3>Methods</h3><p dir="ltr">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.</p><p><br></p><h3>Results</h3><p dir="ltr">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.</p><p><br></p><h3>Conclusion</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Clinics and Research in Hepatology and Gastroenterology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.clinre.2024.102357" target="_blank">https://dx.doi.org/10.1016/j.clinre.2024.102357</a></p>2024-06-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.clinre.2024.102357https://figshare.com/articles/journal_contribution/Efficacy_and_safety_of_aldafermin_in_non-alcoholic_steatohepatitis_A_systematic_review_and_meta-analysis_of_randomized_controlled_trials/25827250CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258272502024-06-01T00:00:00Z |
| spellingShingle | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials Mohamed Mahmoud Marey (18560902) Biomedical and clinical sciences Clinical sciences NAFLD NASH Fatty liver Aldafermin FGF19 |
| status_str | publishedVersion |
| title | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| title_full | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| title_fullStr | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| title_full_unstemmed | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| title_short | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| title_sort | Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials |
| topic | Biomedical and clinical sciences Clinical sciences NAFLD NASH Fatty liver Aldafermin FGF19 |