Dear Editor,
We would like to sincerely thank Dr. Mathias Jachs and Dr. Mattias Mandorfer for their valuable and insightful comments regarding our recently published paper titled “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis” [
1,
2]. Their comments not only highlighted our contribution in investigating the prognosis meaning of non-invasive tests (NITs) in HBV-related cirrhosis, but also provided profound insights into the limitation of our research as well as potential future research directions in this field.
We fully agree with Drs Jachs and Mandorfer’s perspective that assessing the risk of liver decompensation in patients with HBV-related compensated cirrhosis using NITs is of critical importance. Our findings confirm that Baveno VII criteria (NITs for clinically significant portal hypertension [CSPH] or endoscopy) [
3] effectively stratify the risk of decompensation in these patients [
1]. The addition of spleen stiffness measurement (SSM) further refines risk stratification, particularly for patients in the “grey zone” (liver stiffness measurement [LSM] 15–25 kPa) [
4]. Preliminary analyses suggest that the Baveno VII criteria may safely rule out HBV-related cirrhosis patients at low risk of decompensation, although further validation is warranted. When combined with SSM, our data shows that the Baveno VI criteria (Baveno VI-SSM, with SSM ≤40 kPa) more effectively identifies HBV-related cirrhosis patients at very low risk of decompensation (<1.0 per 1,000 person-years) compared to other non-invasive models. Furthermore, endoscopy assessment following the Baveno VI-SSM model more specifically identify high-risk patients for decompensation compared with other non-invasive models did [
1].
As noticed, the 2-year decompensation rate of 8% in our HBV cohort reflects the protective effects on portal hypertension events with sustained HBV suppression [
5]. By contrast, patients with alcoholic liver disease (ALD) exhibit a decompensation rate approaching 20% [
6]. Consistent with previous reports, the incidence of decompensation in our patients with hepatitis B cirrhosis undergoing long-term antiviral therapy is relatively low [
7]. This suggests that patients who have received antiviral treatment or are on long-term antiviral therapy are the most suitable candidates for noninvasive screening and surveillance. However, it is also essential to further validate non-invasive methods in the context of ALD or metabolic associated steatosis liver disease.
We appreciate the discussion regarding the technical failure rate that was raised. Indeed, the technical failure rate of SSM in our study was very low, which may be attributed to the relatively low body mass index (BMI) of our cohort. High success rate with @50 Hz probe has been shown in our previous study [
8]. Our previous data showed that the SSM@100Hz probe performed better than the SSM@50Hz probe in ruling out unnecessary endoscopy screening [
9]. We further validated that the new spleen-dedicated probe have excellent success rate in patients with chronic liver diseases, even in liver-health population [
10]. Therefore, we recommend the use of the SSM@100Hz probe for obese populations and suggest that future studies should further investigate the applicability and accuracy of the SSM@100Hz probe in patients with varying BMI levels.
As Drs Jachs and Mandorfer pointed out, with the increasing use of non-invasive screening in patients with liver disease and the earlier detection and management of those at high risk of decompensation, hepatocellular carcinoma (HCC) is expected to become more prevalent than decompensation in future follow-ups [
11]. There is also a clear need to develop NITs-based models for assessing HCC risk. Additionally, they highlighted the low rates of non-selective β-blocker (NSBB) use and endoscopic variceal ligation in patients with high-risk varices. We acknowledge that primary prophylaxis for variceal bleeding in HRV patients was the standard of care worldwide during the study period [
2]. In our study, while there is evidence supporting the use of NSBB or ligation, practical challenges remain. These challenges stem from both physician hesitancy (e.g., overestimation of side effects, habit of using NSBB) and patient factors (e.g., adherence, hypotension, fatigue) observed [
12]. Although this reflects deviations from guideline recommendations, it also highlights the real-world challenges of primary prevention of cirrhotic portal hypertension [
13]. Some guidelines have highlighted regional differences in patient adherence, emphasizing the need for implementation research [
14]. In addition, tailored patient education and simplified monitoring protocols have the potential to enhance compliance. To address these issues, additional education and training initiatives are being implemented to increase awareness and acceptance of these strategies among treating physicians. Finally, more optimal recommendation for NSBB in HRV patients should be searched considering the much low probability of decompensation events (43.2 per 1,000 person-year) in HBV-related cirrhosis patients.
High-risk patients require invasive procedures, such as endoscopy or hepatic venous pressure gradient (HVPG) measurement, to assess whether NSBB therapy should be initiated. However, not all high-risk cirrhotic patients are able to undergo these tests. Consequently, patients in need of primary prevention may not be identified or treated promptly. Currently, there is insufficient evidence to support the use of non-invasive methods for guiding the initiation of primary prevention. Importantly, our data reflect real-world clinical scenarios, providing valuable insights into the current management of varices in cirrhotic patients
Unfortunately, we did not have HVPG data in our cohort to verify the direct association of NITs with portal pressure. Since the Baveno VII consensus, non-invasive screening methods have been widely adopted in clinical practice. While HVPG is considered for high-risk patients, its high invasiveness and complexity limit its widespread acceptance among patients. We have validated that SSM@100Hz >50 kPa has excellent capability to diagnose clinical significant portal hypertension defined as HVPG ≥10 mmHg [
15], and longitudinal studies are needed to endorse SSM-guided NSBB initiation. Our cohort is still under follow-up, and the prognostic value of longitudinal NITs will be further explored once a sufficient number of events are available.
In conclusion, our goal is to integrate NITs with treatment strategies in the management of HBV cirrhosis, thereby bridging the gap between ‘testing’ and ‘intervention.’ Meanwhile, we recognize the need to address the undertreatment of high-risk patients in our study, though which does not diminish the value of our work in providing guidance for the management of HBV-related cirrhosis.
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), Nat ional Science and Technology Major Project (2018ZX10723203), National Natural Science Foundation of China (82070650, 82370614), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S131), 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).
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Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
clinically significant portal hypertension
hepatic venous pressure gradient
liver stiffness measurement
spleen stiffness measurement
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Citations
Citations to this article as recorded by
- Reply to correspondence on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
Mathias Jachs, Mattias Mandorfer
Clinical and Molecular Hepatology.2026; 32(1): e106. CrossRef
