Discussion
The Baveno VII criteria is recently validated as a non-invasive tool for detecting CSPH;18 however, the diagnosis of CSPH grey zone remained suboptimal to identify cirrhotic patients for NSBBs treatment to prevent decompensation.18 In this study, we developed a novel CSPH risk model to better stratify the CSPH among cirrhotic patients, with a higher AUC than ANTICIPATE model and Baveno VII criteria to identify CSPH. Most importantly, we demonstrated that treatment with carvedilol significantly reduces the 3-year cumulative incidence of decompensation (primarily ascites) among the high-risk CSPH patients, which provided much-needed evidence of using carvedilol in cirrhotic patients with CSPH.
Currently, non-invasive tools for CSPH stratification are the mainstream trend. It is well known that HVPG ≥10 mmHg is the gold standard to determine the presence of CSPH in patients with viral- and alcohol-related cirrhosis. Given that HVPG is an invasive measurement, more and more non-invasive tests have been proven as a surrogate of HVPG for the diagnosis or prediction of CSPH.2,4-9,19-21Among these non-invasive markers, LSM and PLT are the most favorable parameters and were employed by Baveno VII criteria, which defined an LSM of ≥25 kPa to rule in and LSM ≤15 kPa plus PLT ≥150×109/L to rule out CSPH, respectively.1 Notably, the meta-analysis of the current study also revealed the significant importance of the non-invasive markers of LSM and PLT. More importantly, based on the results of the meta-analysis, we established a novel CSPH risk model, and additionally, we found that the AUC of this novel model was higher and the grey zone was smaller when compared with the Baveno VII criteria for the CSPH identification.
The role of non-invasive tools in stratifying decompensation events is currently widely studied. Subsequently, given patients with CSPH are at increased risk of decompensation events, 1,22 the performance of decompensation stratification was an important issue after the development of a non-invasive CSPH diagnosis tool.4,15,16,23-26 In the current study, the high-risk CSPH patients stratified by the novel CSPH risk model presented significantly higher rates (15.8%) of decompensation than the CSPH medium (2.5%) and low (1.7%) risk patients in the follow-up cohort. Notably, the CSPH medium and low-risk subgroups had similarly low rates (2.5% vs 1.7%) of decompensation during a mean follow-up duration of 39.0 (25.2-55.2) months, which synergistically indicates the favorable performance of the novel CSPH risk model.
Finally, it is well known that NSBBs (carvedilol is more favorable) treatment can prevent decompensation in patients with CSPH; therefore, NSBBs therapy should be initiated in patients with CSPH1,27,28; and a favorable non-invasive CSPH stratification tool is expected to fulfil the mission of guiding the response of NSBBs therapy in patients with high-risk CSPH. According to the Baveno VII consensus, assessing the emerging non-invasive methods to diagnose CSPH and determine response to NSBBs is on the research agenda.1 Meanwhile, and unfortunately, studies are limited in this field, and there is an ongoing need to non-invasively identify patients who may benefit from NSBBs to prevent decompensation.29 Remarkably and excitingly, in this study, we found that the high-risk CSPH patients stratified by the novel CSPH risk model and treated with carvedilol had significantly lower rates of decompensation than those of NSBBs untreated high-risk CSPH patients. Further analysis revealed that the most common decompensation event decreased by carvedilol was the ascites, which was consistent with previous studies.3,30
We acknowledge that limitations were in our study. Firstly, the sample size of the retrospective cohort of cirrhotic patients treated with carvedilol is rather small. Nevertheless, we demonstrated that treatment with carvedilol was associated with a significantly lower incidence of hepatic decompensation among high-risk CSPH patients. Secondly, we lack granular data in this large cohort of cirrhotic patients concerning alcohol intake and changes in body weight over time. Thirdly, the sample of patient with non-alcoholic steatohepatitis is limited. Lastly, given that our cohort was predominantly viral-related cirrhosis, further validation is required among cirrhotic patients with non-viral etiology.
In conclusion, we developed a novel non-invasive model to better risk-stratify the CSPH and subsequent decompensation events among patients with liver cirrhosis. Treatment with carvedilol among high-risk CSPH patients stratified by the novel model significantly reduces the risk of hepatic decompensation.