To develop a novel non-invasive model for predicting clinically significant portal hypertension (CSPH) in patients with liver cirrhosis, and investigate whether carvedilol therapy could reduce the risk of hepatic decompensation in patients with high-risk CSPH stratified by the novel non-invasive model. Methods A total of 1,304 patients with liver cirrhosis were enrolled in the study. Non-invasive risk factors of CSPH were identified by a systemic review and meta-analysis of studies containing patients with hepatic venous pressure gradient (HVPG)-proved CSPH. Results A total of six studies from the meta-analysis were involved in this study (n=819), and liver stiffness measurement (LSM) and platelet count (PLT) were eventually identified as independent risk factors of CSPH. A novel CSPH risk model was established as follows: 0.095310×LSM (kPa)-0.01005×PLT (×10^9/L)-0.11, and the cutoff values of >0 (high-risk) and <-0.68 (low-risk) were used to rule in and out CSPH, respectively. In the HVPG cohort (n=151), the areas under the receiver operating characteristic curve (IDDF2023-ABS-0098-Figure 1. Performance of different models for diagnosis of clinically significant portal hypertension) of the novel model, ANTICIPATE model, and Baveno VII criteria for stratifying CSPH were 0.91(0.86-0.95), 0.80(0.73-0.87), and 0.83(0.77-0.89). In the follow-up cohort (n=1,102), the cumulative incidences (1.7% vs 2.5% vs 15.8%) of decompensation events were significantly different by using the novel model cutoff values of >0, 0 to -0.68 (medium-risk), and <-0.68 (IDDF2023-ABS-0098 Figure 2. The cumulative incidence of liver decompensation in follow-up cohort, p<0.001). Remarkably, in the carvedilol-treating cohort, the patients with high-risk CSPH stratified by the novel model and treated with carvedilol (treating cohort, n=51) had significantly lower rates of decompensation events than those of non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=102 after PSM, (IDDF2023-ABS-0098 Figure 3. Decompensation according to treatment group (A) Cumulative incidence of decompensation before propensity score matching PSM (B) Cumulative incidence of decompensation after PSM), all p<0.05). Conclusions A novel non-invasive model has favorable CSPH and subsequent decompensation stratification in patients with liver cirrhosis. Treatment with carvedilol among high-risk CSPH patients stratified by the novel model significantly reduces the risk of hepatic decompensation. • Download figure • Open in new tab • Download powerpoint Abstract IDDF2023-ABS-0098 Figure 1 Performance of different models for diagnosis of clinically significant portal hypertension • Download figure • Open in new tab • Download powerpoint Abstract IDDF2023-ABS-0098 Figure 2 The cumulative incidence of liver decompensation in follow-up cohort, p<0.001 • Download figure • Open in new tab • Download powerpoint Abstract IDDF2023-ABS-0098 Figure 3 Decompensation according to treatment group. (A) Cumulative incidence of decompensation before propensity score matching PSM. (B) Cumulative incidence of decompensation after PSM