Dear Editor,
We read with great interest the recent study by Kim et al. [
1], which provides a comprehensive analysis of the prevalence of steatotic liver disease (SLD) and fibrosis using liver elastography data from the two most recent National Health and Nutrition Examination Survey (NHANES) cycles. This study offers valuable insights into the burden of SLD and several subcategories, including metabolic dysfunction-associated steatotic liver disease, metabolic and alcohol-related liver disease, and alcohol-related liver disease (ALD), while also exploring their associations with demographic, lifestyle, and metabolic indicators. However, we believe several aspects could be further refined to enhance the robustness and applicability of the findings.
First, the study population selection deserves further discussion. The inclusion of alcohol consumption and cardiometabolic variables to account for confounding effects on liver outcomes is commendable. However, the exclusion of other liver diseases, such as viral and autoimmune hepatitis, which may exacerbate liver fibrosis [
2,
3], and extreme obesity (body mass index >30 kg/m
2) and acute liver inflammation can affect liver stiffness, thereby overestimating the burden of liver fibrosis due to SLD alone. Viral hepatitis status can be determined using NHANES laboratory markers (e.g., hepatitis B surface antigen, hepatitis C RNA), whereas autoimmune hepatitis can be assessed through self-reported questionnaire data. Importantly, the absence of viral hepatitis data in the 2021–2023 cycles limits the ability to exclude participants with viral hepatitis. Baseline liver function tests and high-sensitivity C-reactive protein (CRP) could serve as alternative markers to identify acute liver inflammation.
Second, the definition of SLD and fibrosis using liver elastography requires careful consideration. While liver elastography is a widely used non-invasive tool, its application is limited by the absence of universally accepted diagnostic thresholds for hepatic steatosis and fibrosis. Operator variability, patient characteristics, and confounding conditions (e.g., inflammation, cholestasis, heart failure) may significantly influence the results. Several studies used the CAP threshold for defining SLD were 248 dB/m [
4], 275 dB/m [
5], 285 dB/m, 300 dB/m [
6], etc., which is quite different from a study based on liver biopsy from the United Kingdom, with the threshold of 302 dB/m, 331 dB/m, and 337 dB/m for S1, S2, and S3, respectively [
7]. And taking 285 dB/m as the threshold to define the burden of SLD remains questionable. while the threshold of LSM is relatively common, 8 kPa for fibrosis threshold, 11.7 kPa or 13.1 kPa for severe fibrosis. Therefore, further integration of advanced imaging modalities such as MRI or CT can provide a more comprehensive assessment of SLD.
Statistically, the study employed NHANES sampling weights and Taylor series linearization to estimate population-level prevalence. However, it is unclear whether the weighting fully accounts for subgroup characteristics, particularly for smaller subgroups like ALD. The authors might consider discussing the potential limitations of weighted analyses, particularly in small subgroup comparisons. Conducting sensitivity analyses using unweighted data or alternative statistical models, such as mixed-effects models or Bayesian approaches, could enhance the robustness of the findings. Addressing these concerns would provide greater confidence for this study.
Finally, the interesting finding that the prevalence changes before and after the COVID-19 pandemic showed a slight decrease during the COVID-19 era. Instead, the prevalence of advanced fibrosis among individuals with SLD increased significantly. This finding enlightens us to further explore pandemic-related lifestyle changes and their impact on metabolic health and liver outcomes. For example, the increased prevalence of advanced fibrosis could be related to pandemic-induced weight gain, dietary changes, reduced physical activity, and increased alcohol consumption, all of which are common consequences of social isolation and stress during the pandemic. Additional analyses incorporating metabolic markers, such as low-density lipoprotein, triglycerides, and their ratios, could provide deeper insights. Furthermore, subgroup analyses stratified by comorbidities such as diabetes, hypertension, and cardiovascular disease could elucidate the complex interplay between metabolic dysfunction and liver health during this period. Furthermore, the potential hepatic effects of COVID-19 infection should not be overlooked, given its possible direct and indirect contributions to liver dysfunction, 14–53% of patients with COVID-19 have been reported to develop some form of hepatic dysfunction [
8]. SARS-CoV-2 infection can induce hepatic steatosis and subsequent liver dysfunction [
9]. However, as a cross-sectional study, the lack of follow-up data limits the ability to establish causation or explore temporal trends.
In conclusion, this study highlights the significant burden of SLD and fibrosis in the U.S. and advocates for enhanced screening and management strategies. Despite NHANES data limitations, the findings remain invaluable to understand the burden of SLD and fibrosis, especially combined with the background of metabolism and alcohol-related liver disease. Future research should integrate advanced imaging modalities, longitudinal datasets, and comprehensive biomarker analyses to further elucidate this topic and refine risk stratification strategies.
FOOTNOTES
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Authors’ contribution
Sisi Yang: conceptualization and manuscript draft. Zhenxuan Ma: critical revision for important intellectual content.
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Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
alcohol-related liver disease
National Health and Nutrition Examination Survey
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