Objective: To develop a novel non-invasive model for CSPH, and investigate whether carvedilol could reduce the risk of decompensation in patients with high-risk CSPH stratified by the novel model. Methods: International multicenter observational study with a median follow-up time of 38 months. Three cohorts were included in study from 6 countries. In this study, a total of 1,304 patients were fulfilled diagnosis of liver cirrhosis. Patients were treated with carvedilol in longitudinal carvedilol-treating cohort. The primary outcome was the development of the first hepatic decompensation . Results: Six studies from the meta-analysis were involved (n=819), and LSM and platelet count (PLT) were identified as independent risk factors of CSPH, with pooled risk ratios of 1.10 (95% confidence interval [CI] 1.06-1.15) and 0.99 (95% CI 0.98-0.99). A novel model was established. In HVPG cohort (n=151), the areas under the receiver operating characteristic curve (AUC) of the novel model, ANTICIPATE model, and Baveno VII criteria for CSPH were 0.91 (95% CI 0.86-0.95), 0.80 (95% CI 0.73-0.87), and 0.83 (95% CI 0.77-0.89). The novel model narrows down the grey zone to 22.5%, significantly lower than 50.3%, using Baveno VII criteria (p<0.001). In 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 (p<0.001). In the carvedilol-treating cohort, the patients with high-risk CSPH stratified by the novel model (treating cohort, n=51) had significantly lower rates of decompensation than those of NSBBs untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=102 after PSM, all p<0.05). Conclusion: A novel model provides stratification for CSPH and decompensation in patients with liver cirrhosis. Treatment with carvedilol significantly reduces the risk of decompensation among high-risk CSPH patients stratified by the novel model.

Background and aims: The type 2 diabetes mellitus (T2DM) is a common comorbidity of chronic hepatitis C (CHC). This study intended to investigate the impact of direct-acting antiviral agents (DAAs)-induced sustained virological response (SVR) on glycometabolism in CHC patients with T2DM. Methods: We searched PubMed, Scopus, Web of Science, and Embase up to July 7th, 2021. Studies reporting the association between DAA-induced SVR and glycometabolism in diabetic patients were retained. Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels before DAA treatment and after SVR were conducted meta-analyses with random-effects models. Results: 1371 potentially relevant articles were screened. Our analysis included 16 studies with data for 5024 patients. A significant improvement was noted in glycemic control in SVR group, with a mean HbA1c reduction of 0.57% (95% CI: 0.46–0.69%; I2=72.8%) and FPG reduction of 22.28mg/dL (95% CI: 13.35–31.21mg/dL; I2=96.18%). Conversely, changes of HbA1c in non-SVR group were a mean increase of 0.03% (95% CI: -0.15–0.22%; I2=68.75%). Subgroup analyses about HbA1c and FPG classified by study type both showed decline of the two indicators after SVR, and especially a reduction of HbA1c, 0.52% (95% CI: 0.39–0.65%; I2=73.5%) in retrospective study subgroup and 0.70% (95% CI: 0.54–0.87%; I2=36.15%) in prospective study subgroup, indicating lower heterogeneity in prospective studies. Egger’s test suggested publication bias in impact of DAAs on FPG, and no publication bias in impact on HbA1c. Sensitivity analyses confirmed robustness of the results. Conclusion: The glyco-metabolic control improved in terms of HbA1c and FPG level after DAA-induced SVR. However, further large and well-designed prospective cohort studies are still warranted and a prolonged follow-up is needed.