Letter: Reflections on the significance of myokines in alcohol-associated liver disease

Abstract

We were intrigued by the recent article published by Kaur et al. in Alimentary Pharmacology & Therapeutics (2024; 00:1-16), which innovatively highlights the significant correlation of myokines with the progression, disease course, and mortality in alcohol-associated liver disease (ALD). The findings emphasise that elevated myostatin and reduced decorin are associated with the deterioration of ALD, suggesting that these myokines could serve as biomarkers for risk stratification and therapeutic decision-making in ALD, thereby holding substantial practical significance for improving patient outcomes.¹

While we commend the rigorous efforts and valuable contributions of this study, we would like to offer some constructive suggestions for further refinement.

Firstly, the sample selected by Kaur may not be sufficiently representative of the entire population of ALD patients, as the study comprised 97.7% male participants, and the ethnic and genetic backgrounds of the subjects were not clearly defined. Existing literature indicates that variations in muscle mass, metabolic rates, and inflammatory responses may differ across racial and ethnic groups, potentially influencing the secretion levels and responsiveness of myokines.² Therefore, conducting appropriate subgroup analyses could enhance the scientific robustness of the findings.

Secondly, the study variables could be further refined. Information regarding prior treatments and medications taken by patients before the study is crucial. Certain medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs, and antibiotics, may affect the levels of myostatin and decorin due to their secretion mechanisms.³ The use of such medications is common among ALD patients with comorbidities. Thus, sensitivity analyses could provide clearer insights into the associations of myokines within specific ALD populations. Additionally, the multivariable predictive model appears to lack control for confounding factors such as economic status, medication use, dietary habits, and genetic background, which may influence the interpretation of the results. Furthermore, the model was not validated on an independent dataset, which could impact its generalizability.

Moreover, as a cross-sectional study, it did not measure the levels of myostatin and decorin over time, which may limit the assessment of their temporal changes and prognostic implications. We are particularly interested in the trends of myokines in the progression and course of ALD, as well as whether their levels change with disease advancement over a longer follow-up period.

Currently, there are no specific therapeutic agents for ALD, and myokines have the potential to become therapeutic targets. Modulating the expression levels of myokines through the TGF-β/Smad and PI3K/Akt signalling pathways may improve hepatic pathological conditions.⁴ Additionally, targeted drug modification and combination therapies aimed at enhancing oxidative processes could promote improvements in myokine levels.⁵

In conclusion, we wish to explore the role of myokines in ALD and even in the context of liver disease in general, with the hope of contributing to the advancement of therapeutic strategies in liver disease management.

Yaomin Wang: writing – original draft; writing – review and editing. Jun Li: writing – review and editing; funding acquisition. Yaling Li: writing – review and editing; funding acquisition.

This work was supported by the National Natural Science Foundation of China (81803019), the Sichuan Science and Technology Program (2022YFS0625, 2022YFS0614), and the strategic cooperation project of scientific and technological between Luzhou People's government and Southwest Medical University (2023LZXNYDJ010).

This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202 and https://doi.org/10.1111/apt.18297 and https://doi.org/10.1111/apt.18329