Correspondence to editorial on “Optimal cutoffs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis”
Article information
Dear Editor,
We appreciate the insightful editorial comments on our recent publication [1] by Zhang and Wong which comprehensively described the strengths, concerns, and suggestions for future research direction [2]. In this correspondence, we address and discuss the issues raised by the authors.
Among non-invasive tests (NITs), transient elastography (TE) and magnetic resonance elastography (MRE) have been extensively studied for their accuracy and utility in evaluating liver fibrosis and are emerging as alternatives to liver biopsy. However, the differences in predictive power for advanced fibrosis and cirrhosis reported by different studies and the lack of an optimal cutoff value have been noted as limitations to the practical application of TE and MRE, emphasizing the need for clinical guidelines that can be applied effectively.
We performed a meta-analysis to evaluate the diagnostic performance and establish optimal cutoff values for advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on TE and MRE applications. Based on 63 studies involving 19,199 participants for TE and 14 studies involving 1,484 participants for MRE, the optimal cutoff values for diagnosing advanced fibrosis were 7.1–7.9 kPa for TE and 3.62–3.8 kPa for MRE. However, as noted by Zhang and Wong, determining whether a meta-analysis is the most suitable method for establishing ideal cutoff values remains challenging. Concerns regarding the reliability of meta-analysis results are valid, especially when confounding factors affecting study participants are controlled inconsistently among studies. In this regard, the individual participant data (IPD) meta-analysis proposed by Zhang and Wong offers a promising alternative for addressing these issues. As shown by the pooled IPD studies [3], IPD meta-analysis addresses several limitations inherent in conventional aggregate data meta-analysis; however, it remains subject to inherent constraints, including retrospective analyses and variability among studies. In addition, having a limited number of individual studies available for inclusion in IPD metaanalyses is common.
TE cutoff values vary depending on the underlying etiology of the liver disease. For example, patients with alcoholrelated liver disease tend to exhibit higher TE cutoff values for diagnosing liver fibrosis compared to patients with other chronic liver diseases at the same fibrosis stage [4,5]. Thus, TE absolute values are affected by the underlying liver disease and are also influenced by confounding factors such as diet, acute hepatic inflammation, congestive heart failure, and biliary disorders [6-8]. Our study focused exclusively on patients with MASLD to minimize the influence of these confounding factors by excluding those with alcohol-related liver disease, other chronic viral hepatitis, and pediatric patients. The analysis excluded studies not using liver biopsy results as a reference standard and those with inadequately controlled confounding factors.
Zhang and Wong emphasized our study’s the clinical implications in their editorial. Our research showed that TE and MRE exhibit excellent diagnostic performance for liver fibrosis. However, for the F1 and F2 fibrosis stages, MRE showed a slightly superior area under the curve compared to TE; both modalities exhibited comparable and high values for F3 and F4 stages. While the research results suggest that MRE is slightly superior to TE for evaluating early liver fibrosis, its immediate application in patients with MASLD should be done cautiously. Clinical guidelines for patients with MASLD recommend starting with the Fibrosis-4 (Fib-4) index. Additional tests to assess fibrotic burden (e.g., TE and MRE) should be performed if advanced fibrosis or cirrhosis is clinically suspected based on ultrasound findings or low platelet counts [9]. While cost-effectiveness should be considered, MRE may be used to monitor liver fibrosis progression closely.
Our systematic review and meta-analysis identified the cutoff values for diagnosing advanced fibrosis patients with MASLD. These results are expected to be clinically useful for confirming advanced fibrosis and as a basis for clinical guidelines. However, as noted by Zhang and Wong, the limitations of a meta-analysis are acknowledged, highlighting the need for further research. Studies combining different NITs or integrating genetic biomarkers for MASLD may provide better information on disease progression and treatment decisions.
Notes
Authors’ contribution
The authors contributed equally to the literature review and manuscript preparation. They approved the final version of the manuscript.
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
AUC
superior area under the curve
CLD
chronic liver disease
Fib-4
Fibrosis-4
MASLD
metabolic dysfunction-associated steatotic liver disease
MRE
magnetic resonance elastography
TE
transient elastography