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.