Liver cirrhosis is a major global health concern, affecting over 110 million people worldwide and contributing to more than 1.3 million deaths annually [
1,
2]. It ranks as the 11th leading cause of mortality globally, with approximately 5–12% of patients with compensated cirrhosis progressing to decompensation each year [
3-
5]. Once decompensation occurs, the prognosis dramatically worsens, with median survival times dropping from over 12 years in compensated cirrhosis to just about 2 years in decompensated cirrhosis [
4-
7]. Among the factors influencing clinical outcomes in these patients, portal hypertension plays a critical role. The gold standard for assessing portal hypertension is the hepatic venous pressure gradient (HVPG), with a threshold of ≥10 mmHg defining clinically significant portal hypertension (CSPH) [
8]. However, HVPG measurement is invasive, costly, and requires specialized training, which limits its routine clinical application [
8]. Therefore, the development of non-invasive risk stratification tools for compensated advanced chronic liver disease (cACLD) patients has become an urgent priority to enable timely interventions and personalized management strategies.
The Baveno VI consensus initially recommended a combination of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) and platelet count (PLT) for non-invasive risk stratification in cACLD patients [
9]. Specifically, patients with LSM <20 kPa and PLT >150×10
9/L were deemed unlikely to have high-risk varices (HRV), allowing them to avoid unnecessary esophagogastroduodenoscopy (EGD). Further validation studies have supported the effectiveness of this model in reducing the need for EGD surveillance [
10,
11]. Recent advances, including the renewing Baveno VII consensus, have introduced spleen stiffness measurement (SSM) as a valuable addition to risk stratification, and the Baveno VI-SSM model, incorporating SSM ≤40 kPa, has been suggested to improve the accuracy of identifying HRV [
12].
In addition to improving risk stratification for varices, the Baveno VII consensus places increased emphasis on the early diagnosis of CSPH, as early pharmacological interventions can significantly improve outcomes. The Baveno VII criteria suggest LSM ≤15 kPa and PLT ≥150×10
9/L to rule out CSPH and LSM ≥25 kPa to rule in CSPH. Additionally, SSM <21 kPa and SSM >50 kPa are proposed to rule out and rule in CSPH, respectively [
12]. Despite these promising developments, a significant challenge remains—the presence of a diagnostic grey zone, where 40–60% of patients do not fit clearly into either high-risk or low-risk categories [
13]. This has led to the development of combined algorithms, such as those incorporating both Baveno VII criteria and SSM, which have shown promise in reducing the grey zone for CSPH [
14].
In the current issue, Wang et al. [
15] present a pivotal study validating the Baveno VI-SSM model for risk stratification in hepatitis B virus (HBV)-related compensated cirrhosis. Over a median follow-up of 30 months, they prospectively enrolled 1,224 patients who underwent VCTE to assess both LSM and SSM, as well as EGD. The study explored liver-related events, including decompensation (e.g., ascites, portal hypertension-related bleeding, or overt hepatic encephalopathy), hepatocellular carcinoma, and mortality. Notably, 493 patients underwent a second evaluation of EGD and VCTE with a median follow-up of 17 months, providing important insights into disease progression.
The study findings are highly encouraging. Using the Baveno VI criteria, 34.6% of patients (424/1,224) were able to avoid EGD screening, and none of these patients experienced decompensation during follow-up. When the Baveno VI-SSM model was applied, 54.2% of patients (664/1,224) were able to avoid EGD screening, and only one decompensation event was observed, at a rate of 0.5 per 1,000 person-years. Compared to other Baveno VII models, the Baveno VII-SSM (with a single cutoff for SSM) demonstrated the greatest ability in identifying patients at low risk of decompensation, classifying 48.4% of patients identified as low-risk. However, the Baveno VI-SSM model identified 54.2% of patients as being at low risk of decompensation, which was significantly higher compared to the Baveno VII-SSM model (
P=0.004). The combination models based on the Baveno VI criteria, Baveno VII criteria, and different cutoff values of SSM are presented in
Table 1.
Further analysis revealed that among 560 patients who underwent EGD due to an unfavored Baveno VI-SSM model, 41.8% (234/560) were diagnosed with HRV, with a decompensation incidence rate of 42.8 per 1,000 person-years. In contrast, the decompensation incidence rate among high-risk patients identified by the Baveno VII-SSM model (single cutoff) was lower than that of patients diagnosed with HRV via EGD screening following the Baveno VI-SSM assessment (42.8 vs. 21.1 per 1,000 person-years, P=0.009). Patients diagnosed with HRV using the Baveno VI-SSM had a significantly higher cumulative incidence of decompensation compared to those identified with CSPH by the Baveno VII-SSM model (single-cutoff) (P<0.001).
The longitudinal follow-up in a subgroup of 493 patients, who underwent repeat EGD assessment after a median of 17 months, further confirmed the utility of the Baveno VI-SSM model. Among the patients who met the Baveno VI-SSM model at baseline, 89.6% (242/270) maintained a favored Baveno VI-SSM status at the second assessment, with only one case of esophageal varices progression and no cases of decompensation observed. Among the 223 patients with an unfavored Baveno VI-SSM status at baseline, 62.8% (140/223) remained with the unfavored status at the second assessment, with 20 experiencing esophageal varices progression and 8 developing decompensation events. Compared with patients with consecutive favored Baveno VI-SSM assessments, those with consecutive unfavorable assessments had a significantly higher rate of esophageal varices progression (99.5 vs. 2.6 per 1,000 person-years, P<0.001) and a greater incidence of decompensation (34.2 vs. 0 per 1,000 person-years, P=0.027). This highlights the prognostic value of repeated, non-invasive evaluations for monitoring cirrhotic patients over time.
However, some limitations in the study should be noted. The cohort was composed solely of HBV-related cirrhosis patients, and it remains uncertain whether the Baveno VI-SSM model would perform similarly in patients with other liver disease etiologies, such as metabolic dysfunction-associated fatty liver disease or alcoholic liver disease. The relatively short median follow-up may not fully capture the long-term trajectory of liver-related events, and longer follow-up periods will be necessary for a comprehensive assessment. Additionally, the study employed the standard 50 Hz VCTE probe for measuring SSM, while the spleen-dedicated 100 Hz probe may offer enhanced accuracy of SSM value, warranting further investigation. Moreover, among the HBV-related cirrhosis patients, 82% had achieved viral suppression under continuous antiviral therapy, while a small proportion did not. The performance of the Baveno VI-SSM model in the subgroup of HBV-related cirrhosis patients with viral suppression has not yet been evaluated.
In clinical practice, the Baveno VI-SSM model holds great promise as a non-invasive, cost-effective tool for risk stratification in HBV-related cirrhosis, allowing clinicians to optimize surveillance and treatment strategies. Its ability to identify patients at low risk for decompensation not only reduces unnecessary EGD procedures, but also facilitates a more targeted approach to pharmacological management for high risk patients. Villanueva et al. [
16,
17] reported that long-term treatment with non-selective beta-blockers (NSBBs) could enhance decompensation-free survival in patients with compensated cirrhosis and CSPH, primarily by reducing the incidence of ascites. Carvedilol, which combines non-selective β-blocking effects with α-1 adrenergic receptor blockade, effectively improves hepatic vascular resistance and is recommended as the preferred NSBB for CSPH [
12,
18]. The HVPG response is defined as a reduction of HVPG ≥10% from baseline or a drop below 12 mmHg [
9]. However, since approximately 25% of patients treated with carvedilol are non-responders [
19,
20], future studies should focus on exploring the SSM-based model to identify patients who would likely benefit from NSBB therapy.
In conclusion, the Baveno VI-SSM model represents a significant advancement in the non-invasive management of portal hypertension in cirrhotic patients. With further validation in broader cohorts and long-term follow-up studies, it has the potential to become a cornerstone of personalized care for patients with compensated cirrhosis, reducing healthcare costs and improving patient outcomes.
FOOTNOTES
-
Authors’ contribution
All authors were responsible for the interpretation of data, the drafting, and the critical revision of the manuscript for
important intellectual content. All authors approved the final
version of the article.
-
Acknowledgements
The Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); Research Personnel Cultivation Programme of Zhongda Hospital Southeast University (CZXM-GSP-RC125, CZXM-GSPRC119); China Postdoctoral Science Foundation (2024M 750461); National Natural Science Foundation of China (82402413); Natural Science Foundation of Jiangsu Province (BK20241681); Health Research Program of Anhui (AHWJ2023A30169).
-
Conflicts of Interest
The authors declare no conflicts of interest.
Table 1.Combination models based on the Baveno VI criteria, Baveno VII criteria, and different cutoff values of SSM for risk stratification
Table 1.
|
Baveno VI/VII criteria |
Method |
|
Baveno VI criteria |
LSM <20 kPa and PLT >150×109/L |
|
Baveno VI-SSM |
(LSM <20 kPa and PLT >150×109/L) or SSM ≤40 kPa |
|
Baveno VII criteria |
|
|
Rule out |
LSM ≤15 kPa and PLT ≥150×109/L |
|
Rule in |
LSM ≥25 kPa |
|
Baveno VII-SSM (single-cutoff) |
|
|
Rule out |
LSM ≤15 kPa; PLT ≥150×109/L; SSM ≤40 kPa |
|
Rule in |
LSM ≥25 kPa; PLT <150×109/L; SSM >40 kPa |
|
Baveno VII-SSM (dual-cutoff) |
|
|
Rule out |
LSM ≤15 kPa; PLT ≥150×109/L; SSM <21 kPa |
|
Rule in |
LSM ≥25 kPa; PLT <150×109/L; SSM >50 kPa |
Abbreviations
compensated advanced chronic liver disease
clinically significant portal hypertension
esophagogastroduodenoscopy
hepatic venous pressure gradient
liver stiffness measurement
non-selective beta-blockers
spleen stiffness measurement
vibration-controlled transient elastography
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