Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content
Background and Aims: This study aims to conduct a comprehensive quantitative analysis of various nonalcoholic fatty liver disease (NAFLD) therapeutics, utilizing magnetic resonance (MR)-detected liver fat content (LFC) as the efficacy endpoint, and to identify biomarkers correlated with changes in L...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Gastro Hep Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572324001894 |
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| author | Haoxiang Zhu Ling Xu Yinhua Lv Juan Yang Jihan Huang Qingshan Zheng Guang Ji Lujin Li |
| author_facet | Haoxiang Zhu Ling Xu Yinhua Lv Juan Yang Jihan Huang Qingshan Zheng Guang Ji Lujin Li |
| author_sort | Haoxiang Zhu |
| collection | DOAJ |
| description | Background and Aims: This study aims to conduct a comprehensive quantitative analysis of various nonalcoholic fatty liver disease (NAFLD) therapeutics, utilizing magnetic resonance (MR)-detected liver fat content (LFC) as the efficacy endpoint, and to identify biomarkers correlated with changes in LFC based on published literature. Methods: We performed a systematic search of public databases for placebo-controlled randomized trials on NAFLD up to September 29, 2023. A random-effects meta-analysis was employed to assess efficacy differences between drugs with various mechanisms and placebo. Initial Pearson correlation analysis explored the relationships between biomarkers and LFC. For biomarkers showing significant correlations with LFC, further modeling analysis was conducted to examine their relationship characteristics. Results: Our analysis included 36 studies with 3222 subjects and 33 investigational drugs, which were categorized into 6 mechanistic groups. Drugs such as fibroblast growth factor agonists, and those targeting adipocytes, inflammation, or fibrosis, showed greater efficacy in reducing LFC compared to Resmetirom, which has an efficacy of reducing LFC by 5.2%. From the 121 biomarkers analyzed, alanine aminotransferase and aspartate aminotransferase demonstrated moderate correlations with LFC; specifically, changes of −5.9 U/L in alanine aminotransferase or −3.3 U/L in aspartate aminotransferase were associated with an additional 1% reduction in LFC. Conclusion: The results of this study provide valuable insights for the clinical development of future NAFLD therapeutics, highlighting the efficacy of specific drug mechanisms and the potential of certain biomarkers as surrogate endpoints. |
| format | Article |
| id | doaj-art-1ff17f8573dd492b954966ce6d946c52 |
| institution | Kabale University |
| issn | 2772-5723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj-art-1ff17f8573dd492b954966ce6d946c522025-02-12T05:33:09ZengElsevierGastro Hep Advances2772-57232025-01-0144100593Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat ContentHaoxiang Zhu0Ling Xu1Yinhua Lv2Juan Yang3Jihan Huang4Qingshan Zheng5Guang Ji6Lujin Li7Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Qingshan Zheng, PhD, Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine (Shanghai University of Traditional Chinese Medicine), Shanghai, China; Guang Ji, PhD, Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine (Shanghai University of Traditional Chinese Medicine), Shanghai, China; Correspondence: Address correspondence to: Lujin Li, PhD, Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.Background and Aims: This study aims to conduct a comprehensive quantitative analysis of various nonalcoholic fatty liver disease (NAFLD) therapeutics, utilizing magnetic resonance (MR)-detected liver fat content (LFC) as the efficacy endpoint, and to identify biomarkers correlated with changes in LFC based on published literature. Methods: We performed a systematic search of public databases for placebo-controlled randomized trials on NAFLD up to September 29, 2023. A random-effects meta-analysis was employed to assess efficacy differences between drugs with various mechanisms and placebo. Initial Pearson correlation analysis explored the relationships between biomarkers and LFC. For biomarkers showing significant correlations with LFC, further modeling analysis was conducted to examine their relationship characteristics. Results: Our analysis included 36 studies with 3222 subjects and 33 investigational drugs, which were categorized into 6 mechanistic groups. Drugs such as fibroblast growth factor agonists, and those targeting adipocytes, inflammation, or fibrosis, showed greater efficacy in reducing LFC compared to Resmetirom, which has an efficacy of reducing LFC by 5.2%. From the 121 biomarkers analyzed, alanine aminotransferase and aspartate aminotransferase demonstrated moderate correlations with LFC; specifically, changes of −5.9 U/L in alanine aminotransferase or −3.3 U/L in aspartate aminotransferase were associated with an additional 1% reduction in LFC. Conclusion: The results of this study provide valuable insights for the clinical development of future NAFLD therapeutics, highlighting the efficacy of specific drug mechanisms and the potential of certain biomarkers as surrogate endpoints.http://www.sciencedirect.com/science/article/pii/S2772572324001894Nonalcoholic fatty liverNonalcoholic steatohepatitisMRI-PDFFMRS-PDFF |
| spellingShingle | Haoxiang Zhu Ling Xu Yinhua Lv Juan Yang Jihan Huang Qingshan Zheng Guang Ji Lujin Li Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content Gastro Hep Advances Nonalcoholic fatty liver Nonalcoholic steatohepatitis MRI-PDFF MRS-PDFF |
| title | Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content |
| title_full | Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content |
| title_fullStr | Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content |
| title_full_unstemmed | Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content |
| title_short | Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content |
| title_sort | comparative efficacy of nafld therapies and biomarker associations a meta analysis based on liver fat content |
| topic | Nonalcoholic fatty liver Nonalcoholic steatohepatitis MRI-PDFF MRS-PDFF |
| url | http://www.sciencedirect.com/science/article/pii/S2772572324001894 |
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