Dear Editor,
We would like to sincerely thank Dr. Bo Zheng and Dr. Lizhou Wang for their insightful comments and valuable suggestions regarding our recent study on the ‘Baveno VISSM model stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis’ [
1]. Their letter underscores several important aspects that merit further discussion, and we are grateful for the opportunity to address these points [
2].
In our study, we utilize a single baseline Baveno VI-SSM assessment to stratify the risk of portal hypertension-related events in patients with HBV-related cirrhosis and investigate the prognostic value of this single assessment. Our goal is not to predict portal hypertension-related events, which carries a different implication.
We acknowledge that rigid thresholds may not fully capture the dynamic continuum of portal hypertension, and that patients near cutoff values (e.g., SSM of 39 vs. 41 kPa) may exhibit overlapping clinical trajectories. However, binary stratification remains clinically invaluable due to its simplicity, accessibility, and ease of implementation, particularly in resource-limited settings. Fixed-threshold approaches, such as the Child-Pugh and MELD scores [
3,
4], have persisted because they provide clear, actionable "yes/no" guidance for frontline clinicians. We appreciate the suggestion to integrate continuous multivariable models to improve the accuracy of risk stratification. This is an active focus of our ongoing research, and we are currently developing continuous algorithms to complement the Baveno VI-SSM framework and further enhance its clinical utility.
We agree that liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) values can be influenced by technical factors and physiological fluctuations. However, we believe that these concerns will be minimized with advances in device technology and the establishment of standardized protocols for LSM and SSM measurements. Additionally, the fluctuation observed in LSM and SSM values can often reflect true changes in disease status [
5,
6]. Even if occasional fluctuations lead to misclassification, repeated non-invasive monitoring is unlikely to result in consistent errors, as the overall trend would remain reliable. We appreciate the suggestion to integrate LSM, SSM, platelet count, alanine aminotransferase trends, and treatment response into a continuous risk prediction model. Indeed, this is an active area of focus in our research. We are currently exploring ways to enhance the accuracy and clinical applicability of the Baveno VI-SSM model and are working towards developing a dynamic, non-invasive prediction model that better captures the progressive and dynamic nature of portal hypertension.
Our study results support the current recommendation of 6-month monitoring intervals for high-risk patients. For lowrisk patients, extending the monitoring interval to 12 or even 18 months may be feasible without compromising safety. However, we acknowledge that further research is necessary to validate this approach, particularly given the relatively small subgroup of 270 patients with favorable Baveno VI-SSM status in our study. We are currently conducting additional analyses and plan to include more patients in future studies to provide a more robust foundation for optimizing monitoring intervals.
We fully acknowledge that the exclusive focus on HBVrelated cirrhosis limits the generalizability of our findings, which represents one of the key limitations of our study [
7-
10]. To address this, we are currently conducting prospective, multicenter studies that include patients with various etiologies of cirrhosis. These studies aim to evaluate the applicability and performance of the Baveno VI-SSM model across diverse patient populations. We believe that validating the model in the context of different etiologies is essential for adapting Baveno-based strategies to the evolving epidemiology of cirrhosis and ensuring equitable care for all patients.
Regarding the management of high-risk patients, we appreciate their comments. Although our study did not delve into detailed management pathways, we did emphasize that high-risk patients should undergo invasive hepatic venous pressure gradient measurement to diagnose clinically significant portal hypertension or to initiate non-selective β-blocker (NSBB) therapy, with close monitoring of their condition. Timely and appropriate symptomatic treatment is essential in the event of complication.
We are also working on integrating Baveno risk stratification with tailored intervention algorithms to offer more comprehensive guidance for clinical practice, particularly in the management of NSBB therapy [
11]. We are exploring noninvasive models to guide NSBB treatment, including determining the threshold for initiating therapy and developing a dynamic non-invasive model for monitoring the response to NSBB. Additionally, we thank the author for their suggestions to incorporated sarcopenia or systemic inflammation scores into the Baveno-SSM model, thereby transformed the static model into a dynamic one to meet clinical requirements. These insights are highly valuable and will significantly inform our future research efforts.
We thank you for highlighting opportunities to evolve the Baveno VI-SSM model. While binary thresholds provide pragmatic clinical anchors today, we are committed to developing integrated continuous-risk tools, etiology-specific validations, and dynamic management pathways. We believe that the ongoing research and refinement of the Baveno VI-SSM model, as well as the incorporation of your suggestions, will contribute to improving the quality and personalization of cirrhosis care.
FOOTNOTES
-
Authors’ contribution
Jinjun Chen: review and edit; Haiyu Wang: writing of the article, review and edit.
-
Acknowledgements
Prof Jinjun Chen is supported by National Key Research and Development Program of China (2022YFC2304800), National Science and Technology Major Project (2018ZX-10723203), National Natural Science Foundation of China (82070650, 82370614), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT-01S131), Clinical Research Program of Nanfang Hospital, Southern Medical University (2018CR037, 2020CR026), Clinical Research Start-up Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD006), President Foundation of Nanfang Hospital, Southern Medical University (2019Z003) and Key-Area Research and Development Program of Guangdong Province (2019B020227004). Dr Haiyu Wang is supported by National Natural Science Foundation of China (82200674), National Postdoctoral Program for Innovative Talents of China (BX20220144) and Postdoctoral Science Foundation of China (2022M711518).
-
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
liver stiffness measurement
spleen stiffness measurement
REFERENCES
- 1. Wang H, Liang W, Zhou L, Song J, Wen B, Wu Q, et al. Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis. Clin Mol Hepatol 2025;31:866-880.
- 2. Zheng B, Wang L. Letter to the editor on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”. Clin Mol Hepatol 2026;32:e141-e143.
- 3. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001;33:464-470.
- 4. Botta F, Giannini E, Romagnoli P, Fasoli A, Malfatti F, Chiarbonello B, et al. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study. Gut 2003;52:134-139.
- 5. Semmler G, Yang Z, Fritz L, Köck F, Hofer BS, Balcar L, et al. Dynamics in liver stiffness measurements predict outcomes in advanced chronic liver disease. Gastroenterology 2023;165:1041-1052.
- 6. Marasco G, Dajti E, Ravaioli F, Alemanni LV, Capuano F, Gjini K, et al. Spleen stiffness measurement for assessing the response to β-blockers therapy for high-risk esophageal varices patients. Hepatol Int 2020;14:850-857.
- 7. Jachs M, Mandorfer M. Predicting decompensation risk in compensated HBV cirrhosis: Eternal sunshine for a spotless mind?: Editorial on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”. Clin Mol Hepatol 2026;32:390-394.
- 8. Wang H, Chen J. Correspondence to editorial 1 on “Baveno VISSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”. Clin Mol Hepatol 2026;32:e58-e61.
- 9. Wang H, Chen J. Correspondence to editorial 2 on “Baveno VISSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”. Clin Mol Hepatol 2026;32:e62-e64.
- 10. Wang H, Chen J. Correspondence to editorial 3 on “Baveno VISSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”. Clin Mol Hepatol 2026;32:e65-e67.
- 11. Wang H, Chen J. The evolution of non-invasive strategies in cirrhosis management-from screening to precision monitoring: Editorial on “Fibrosis-4plus score: a novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): an international multicenter study”. Clin Mol Hepatol 2026;32:403-406.
Citations
Citations to this article as recorded by
