Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”

Article information

Clin Mol Hepatol. 2024;30(4):1039-1041

Publication date (electronic) : 2024 September 24

doi : https://doi.org/10.3350/cmh.2024.0801

Tian-Yi Ren¹, Mohammed Eslam², Jian-Gao Fan^,1,3

¹Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

²Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia

³Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China

Corresponding author : Jian-Gao Fan Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, 1665 Kong Jiang Rd, Shanghai 200092, China Tel: +86-21-25077340, Fax: +86-21-25077340, E-mail: fanjiangao@xinhuamed.com.cn

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2024 September 14; Accepted 2024 September 22.

Dear Editor,

We recently wrote an editorial [1] regarding the significant work of Park et al. and now we are pleased to read their valuable correspondence [2]. Obviously, both teams were interested in fibrosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and relevant therapeutic options. Fibrosis secondary to steatohepatitis serves as an important indicator to predict the adverse outcomes of MASLD [3]. Type 2 diabetes mellitus (T2DM) is the independent risk factor for liver fibrosis and cirrhosis [4], and antidiabetic drugs have also shown therapeutic effects in relieving liver fibrosis, especially in the scenario of MASLD [5]. Based on this network meta-analysis that enrolled numerous latest clinical trials, we inferred that glucagon-like peptide-1 receptor agonist (GLP-1RA) based therapy may be superior to thiazolidinediones (TZD) in managing MASLD-related fibrosis. As emphasized by the authors in their correspondence, baseline fibrosis stage of MASLD patients may influence the anti-fibrotic performance of GLP-1RAs and TZDs. We totally agree that further clinical trials stratifying MASLD patients by baseline fibrosis stage would lead to convictive conclusions about the efficacy of GLP-1RAs on liver fibrosis.

Another issue to discuss is the inconsistence between proton magnetic resonance spectroscopy (MRS) and controlled attenuation parameter (CAP) of FibroScan in reflecting treatment effects of GLP-1RAs and TZDs [6]. We agree with the authors that MRS is accurate and effective in assessing hepatic steatosis. According to an early meta-analysis, magnetic resonance-based techniques showed excellent powers in grading steatosis, as reflected by the area under the curve (AUC) over 0.9 [7]. From the perspective of cost performance, convenience and generalization degree in clinical practice, ultrasound-based measures like FibroScan surely maintain some advantages in MASLD screening. However, we must admit that the ability of FibroScan in grading liver steatosis of MASLD patients is suboptimal, when compared with MRS. As shown in a recent meta-analysis, the AUCs for grading liver steatosis using CAP were only 0.74 for S >1 and 0.71 for S >2, respectively [8]. In contrast, ultrasound-based techniques may be highly applicable in determining MASLD-related fibrosis. According to a newly published head-to-head study, FibroScan-aspartate aminotransferase (AST) score showed comparable diagnostic accuracy for fibrotic metabolic dysfunction-associated steatohepatitis (MASH) when compared with magnetic resonance imaging-AST score, and even outperformed the latter measure considering the percentage of correctly classified patients who should have avoided liver biopsy [9]. Based on these findings, it is therefore of supreme importance that novel diagnostic algorisms combining multiple noninvasive tools for MASLD and MASH should be developed [10]. Furthermore, the inaccuracy of CAP for grading liver steatosis in overweight/obese patients [11] may be the breakthrough point of technological innovation in the future.

At last, authors responded to our concern for non-obese and lean MASLD subjects. Lean MASLD is associated with worse clinical outcomes compared to obese and overweight MASLD [12]. For this special population, visceral fat restriction and muscle profile improvement may be more important than simple reduction of body weight [13]. Authors emphasized the capacity of GLP-1RAs in reducing visceral fat mass of MASLD patients, but it’s also worth mentioning that incretin-based therapy might cause rapid and significant loss of lean body mass, which mimics the senescence of muscle [14]. Similarly, incretin-based therapy showed better efficacy in controlling diabetic parameters and reducing cardiometabolic risks in obese T2DM subjects than nonobese T2DM counterparts [15]. We agree with the authors that both the pathogenic mechanisms of non-obese/lean MASLD and the true responses of this subpopulation to current-available therapies need more attention in future studies.

To sum up, we really appreciate Park et al. for sharing their wonderful work that supports incretin-based therapy in MASLD management. This study indeed inspired readers to think deeply about diagnosis, treatment and prognosis of MASLD.