Clin Mol Hepatol > Volume 30(4); 2024 > Article
Ren, Eslam, and Fan: Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
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.

FOOTNOTES

Authors’ contribution
Tian-Yi Ren drafted the manuscript. Mohammed Eslam and Jian-Gao Fan reviewed and finalized the manuscript.
Conflicts of Interest
The authors have no conflicts to disclose.

Abbreviations

AUC
area under the curve
CAP
controlled attenuation parameter
GLP-1RA
glucagon-like peptide-1 receptor agonist
MASH
metabolic dysfunction-associated steatohepatitis
MASLD
metabolic dysfunction-associated steatotic liver disease
MRS
magnetic resonance spectroscopy
T2DM
type 2 diabetes mellitus
TZD
thiazolidinedione

REFERENCES

1. Ren TY, Eslam M, Fan JG. Incretin-based therapy in the management of metabolic dysfunction-associated steatotic liver disease (MASLD): one piece of the puzzle: Editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis”. Clin Mol Hepatol 2024;30:649-652.
crossref pdf
2. Kim H, Park MJ, Kim MG, Kim K. Correspondence to editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”. Clin Mol Hepatol 2024;30:989-991.
crossref pdf
3. Le MH, Le DM, Baez TC, Dang H, Nguyen VH, Lee K, et al. Global incidence of adverse clinical events in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Clin Mol Hepatol 2024;30:235-246.
crossref pmid pmc pdf
4. Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023;29:51-64.
crossref pmid pdf
5. Kim KS, Lee BW. Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease. Clin Mol Hepatol 2020;26:430-443.
crossref pmid pmc pdf
6. Park MJ, Kim H, Kim MG, Kim K. Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis. Clin Mol Hepatol 2023;29:693-704.
crossref pmid pmc pdf
7. Qu Y, Li M, Hamilton G, Zhang YN, Song B. Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis. Eur Radiol 2019;29:5180-5189.
crossref pmid pdf
8. Petroff D, Blank V, Newsome PN, Voican CS, Thiele M, et al. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol 2021;6:185-198.
crossref pmid
9. Castera L, Garteiser P, Laouenan C, Vidal-Trécan T, Vallet-Pichard A, Manchon P, et al. Prospective head-to-head comparison of non-invasive scores for diagnosis of fibrotic MASH in patients with type 2 diabetes. J Hepatol 2024;81:195-206.
pmid
10. Zhang S, Mak LY, Yuen MF, Seto WK. Screening strategy for non-alcoholic fatty liver disease. Clin Mol Hepatol 2023;29(Suppl):S103-S122.
crossref pmid pdf
11. Myers RP, Pollett A, Kirsch R, Pomier-Layrargues G, Beaton M, Levstik M, et al. Controlled Attenuation Parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography. Liver Int 2012;32:902-910.
crossref pmid
12. Sato-Espinoza K, Chotiprasidhi P, Huaman MR, Díaz-Ferrer J. Update in lean metabolic dysfunction-associated steatotic liver disease. World J Hepatol 2024;16:452-464.
pmid pmc
13. Kim HK, Bae SJ, Lee MJ, Kim EH, Park H, Kim HS, et al. Association of visceral fat obesity, sarcopenia, and myosteatosis with non-alcoholic fatty liver disease without obesity. Clin Mol Hepatol 2023;29:987-1001.
crossref pmid pmc pdf
14. Locatelli JC, Costa JG, Haynes A, Naylor LH, Fegan PG, Yeap BB, et al. Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? Diabetes Care 2024;47:1718-1730.
crossref pmid pdf
15. Nikolic D, Patti AM, Giglio RV, Chianetta R, Castellino G, Magán-Fernández A, et al. Liraglutide improved cardiometabolic parameters more in obese than in non-obese patients with type 2 diabetes: a real-world 18-month prospective study. Diabetes Ther 2022;13:453-464.
crossref pmid pmc pdf

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