Letter: Association of Myokines With Disease Progression and Outcomes in Patients With Alcohol-Associated Liver Disease—Authors' Reply'

We are deeply grateful to Zhou et al. [1] and Wang et al. [2] for their thoughtful reflections on our study exploring the association of myokines with disease progression and outcomes in alcohol-associated liver disease (ALD) [3]. Zhou et al.'s recent findings in primary biliary cholangitis (PBC) reinforce the broader relevance of myokines as potential biomarkers, extending their utility across diverse chronic liver diseases [1]. We concur with their observation that myostatin and decorin alterations may represent common pathophysiological mechanisms beyond ALD, further supporting their potential for risk stratification and therapeutic targeting.

We acknowledge the concerns raised by Wang et al. regarding the predominance of male participants in our cohort (97.7%) [2]. As noted, this imbalance reflects the known higher prevalence of ALD in males [4]. Nonetheless, we agree that future studies should include more diverse populations to account for gender, racial and ethnic differences in muscle mass, metabolism and inflammation. These factors are critical in evaluating myokine profiles across varying demographic groups. Zhou et al.'s findings in PBC, despite differences in aetiology and patient diversity, demonstrate similar myokine alterations, reinforcing the need for further exploration in multiple liver disease contexts [1].

Regarding medication use, we appreciate Wang et al.'s concern that drugs such as glucocorticoids, NSAIDs, and antibiotics may affect myokine levels [2]. Considering the suggestion, in our multivariable models, we accounted for prior antibiotic and steroid use in ALD patients with acute decompensation (AD) and acute-on-chronic liver failure (ACLF), and our results remained consistent (Table 1). We agree that a broader assessment of other potential confounders such as socioeconomic status, dietary habits and genetic background would enhance the robustness of future analyses.

The absence of longitudinal data and external validation is a limitation of our current work. Cross-sectional measurements, while useful, cannot capture the dynamic nature of myokine fluctuations over the disease course. We fully support further longitudinal studies to better understand temporal changes in myokine levels and their potential role in guiding treatment decisions. As highlighted by Zhou et al. understanding the progression of myostatin and decorin levels could offer valuable prognostic insights in ALD and beyond [1].

In conclusion, we appreciate the valuable feedback from both Zhou et al. and Wang et al. Their work underscores the potential of myokines as biomarkers across liver diseases and highlights the need for diverse and longitudinal studies to further validate these findings. We look forward to continued research that advances our understanding of myokine biology and its application in clinical practice.

Parminder Kaur: formal analysis, writing – original draft. Pratibha Garg: writing – review and editing. Nipun Verma: conceptualization, writing – review and editing.

This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202, https://doi.org/10.1111/apt.18285 and https://doi.org/10.1111/apt.18297.