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IntroductionPatients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%–6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy.Methods and analysisThis study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.Ethics and disseminationThe study protocol has been approved by the ethics committees of the Sixth People’s Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.Trial registration numberChiCTR2300073864.

Portal hypertension (PH) is the initial and main consequence of liver cirrhosis. Hepatic venous pressure gradient (HVPG) measurement has been widely used to estimate portal pressure gradient (PPG) and detect portal hypertension. However, some clinical studies have found poor correlation between HVPG and PPG, which may lead to the misdiagnosis of portal hypertension. In this study, we provided a method to evaluate patients’ PPG based on clinically measured HVPG with computational fluid dynamics (CFD). Twenty-five patients who underwent HVPG measurement were recruit for analysis. Results show that HVPG significantly correlates with PPG (R = 0.7499, P < 0.0001), with an accuracy to distinguish clinically significant portal hypertension (CSPH) as high as 92 %. However, PH severity classification was underestimated for 36 % patients, especially for patients with hepatic venous collateral formation and presinusoidal portal vein occlusion. It is concluded that HVPG is a relatively reliable diagnostic method for PH when PPG cannot be directly measured. For patients who have clinical symptoms of PH but their HVPG are within a normal range, numerical evaluation of PPG with CFD is an excellent way for their diagnosis.

BackgroundA high portal pressure gradient (PPG) is associated with an increased risk of failure to control esophagogastric variceal hemorrhage and refractory ascites in patients with decompensated cirrhosis. However, direct measurement of PPG is invasive, limiting its routine use in clinical practice. Consequently, there is an urgent need for non-invasive techniques to assess PPG.AimTo develop and validate a deep learning model that predicts PPG values for patients with decompensated cirrhosis and identifies those with high-risk portal hypertension (HRPH), who may benefit from early transjugular intrahepatic portosystemic shunt (TIPS) intervention.MethodsData of 520 decompensated cirrhosis patients who underwent TIPS between June 2014 and December 2022 were retrospectively analyzed. Laboratory and imaging parameters were used to develop an artificial neural network model for predicting PPG, with feature selection via recursive feature elimination for comparison experiments. The best performing model was tested by external validation.ResultsAfter excluding 92 patients, 428 were included in the final analysis. A series of comparison experiments demonstrated that a three-parameter (3P) model, which includes the international normalized ratio, portal vein diameter, and white blood cell count, achieved the highest accuracy of 87.5%. In two distinct external datasets, the model attained accuracy rates of 85.40% and 90.80%, respectively. It also showed notable ability to distinguish HRPH with an AUROC of 0.842 in external validation.ConclusionThe developed 3P model could predict PPG values for decompensated cirrhosis patients and could effectively distinguish HRPH.

Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response. Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events. The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death. Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.

Background and aims To introduce and assess a novel method for portal pressure measurement based on biofluid mechanics in portal hypertensive patients undergoing surgery. Methods The research was a multi-center, retrospective study, conducted on patients who underwent surgery and measurement of free portal pressure (FPP). There were 118 patients included and 21 patients excluded due to the failure or poor results of Doppler ultrasound, and 97 patients were screened. We used patients’ CT images, Doppler ultrasound results of the portal system, blood density and viscosity to reconstruct their portal system and simulate its internal blood flow. According to the patient’s physical property, geometry, and boundary conditions, the Navier–Stokes equations were solved by FLUENT software, and virtual free portal pressure (vFPP) was calculated. Finally, the Bland–Altman Limits of Agreement, intraclass correlation coefficient (ICC), and the Lin’s concordance correlation coefficient were performed to evaluate the numerical correlation between the vFPP and FPP. Results All patients enrolled in this study underwent the surgery, and the FPP of patients was measured during the surgery, with a mean FPP of 22.8 ± 3.3 mmHg (range: 13–33 mmHg). Meanwhile, according to computational biofluid mechanics, all patients’ vFPP was calculated. Then, we further explored whether there was a close relationship between vFPP and FPP in the whole population. For the analysis of Bland–Altman Limits of Agreement, the mean value of difference was − 0.1569 (95% CI: − 0.4305 to 0.1167); lower limit of agreement: − 2.8176 (95% CI: − 3.2868 to − 2.3484); upper limit of agreement: 2.5038 (95% CI: 2.0346 to 2.9730). The ICC was 0.9215 (95% CI: 0.8848 to 0.9468). Furthermore, the Lin’s concordance correlation coefficient showed a numerical correlation between the vFPP and FPP, which was 0.9205 (95% CI: 0.8840 to 0.9459). All these results confirmed that our vFPP model could provide an accurate prediction of FPP in patients. Conclusions The vFPP of patients calculated by computational biofluid mechanics was significantly correlated with the FPP of portal hypertensive patients, which would be a novel, non-invasive, and accurate method for the assessment of portal pressure in surgical patients.

Objective To evaluate the correlation and consistency between hepatic venous pressure gradient(F-HVPG) calculated as the wedged hepatic venous pressure (WHVP) minus free hepatic venous pressure (FHVP), I-HVPG calculated as WHVP minus inferior vena cava pressure (IVCP) in the hepatic segment, and portal pressure gradient (PPG). Methods Data were collected from 112 patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt (TIPS) along with HVPG measurement. FHVP, IVCP, WHVP, and portal venous pressure (PVP) were collected intraoperatively. Pearson’s correlation and Bland–Altman method were used to assess correlation and consistency. Results A total of 112 patients were retrospectively collected. The correlation coefficient (r) values ( p  < 0.001) between FHVP and IVCP, WHVP and PVP, F-HVPG and I-HVPG, F-HVPG and PPG, I-HVPG and PPG were 0.835, 0.717, 0.946, 0.667 and 0.698, respectively; the determination coefficient (R 2 ) values were 0.697, 0.514, 0.895, 0.445 and 0.487, respectively. Bland–Altman plots showed that F-HVPG and I-HVPG had the narrowest 95% limits of agreement. Among patients with FHVP-IVCP > 2 mmHg, the (r) values ( p  < 0.05) between F-HVPG and I-HVPG, F-HVPG and PPG, I-HVPG and PPG were 0.907, 0.648 and 0.807, respectively; the (R 2 ) values were 0.822, 0.420 and 0.651, respectively. Bland–Altman plots showed that I-HVPG had the narrower 95% limits of agreement with PPG. Conclusion F-HVPG and I-HVPG demonstrated high correlation and consistency. I-HVPG consistently correlates more closely with PPG than F-HVPG, both in the overall cohort and in patients with FHVP-IVCP > 2 mmHg. These results suggest that I-HVPG may serve as a more reliable alternative. Due to the significant underestimation of the PPG, HVPG measurement should not be used to exclude patients from a TIPS intervention.

Background Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated. Methods One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6 weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG ≤ 12 mmHg. Results Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4 ± 16.5 vs. 70.3 ± 7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21 ± 5 vs. 26 ± 5 vs. 26 ± 4 mmHg). The correlation of LS and HVPG was stronger in controls with HVPG ≤ 12 mmHg ( R  = 0.951; P  < 0.0001) than in patients with HVPG > 12 mmHg ( R  = 0.538; P  = 0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS ( R  = 0.930; P  < 0.0001). Forty-three percent (53/122) of patients were hemodynamic responders to NSBB. The improvement in the correlation of LS and HVPG under NSBB was mainly noted in hemodynamic responders ( R  = 0.864), but not in nonresponders ( R  = 0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders. Conclusions Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG > 12 mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.

Background Accurate estimation of the hepatic functional reserve before liver resection is important to avoid post-hepatectomy liver failure (PHLF). The aim of the present study was to evaluate the association of indocyanine green retention test with portal pressure by the cause of cirrhosis (non-viral vs. viral) and assessed postoperative outcomes including incidence of PHLF in patients with viral and non-viral cirrhosis. Methods The cohort includes 50 consecutive patients with liver cirrhosis scheduled for liver resection for primary liver tumors at the Lausanne University Hospital between 2009 and 2018. Results There were 31 patients with non-viral liver cirrhosis (Non-virus group) and 19 with viral liver cirrhosis (virus group). The indocyanine green retention rate at 15 min (ICG-R15) ( p  = 0.276), Hepatic Venous Portal Gradient (HVPG; p  = 0.301), and postoperative outcomes did not differ between the non-virus group and viral group. ICG-R15 and HVPG showed a significant linear correlation in all patients (Spearman’s rank correlation coefficient, ρ  = 0.599, p  < 0.001), the non-virus group ( ρ  = 0.555, p  = 0.026), and the virus group ( ρ  = 0.534, p  = 0.007). A receiver operating characteristic curve analysis showed that ICG-R15 was a predictor for presence of portal hypertension (PH; HVPG ≥ 12 mmHg) (area under the curve [AUC] = 0.780). The cut-off value of ICG-R15 for predicting the presence of PH was 16.0% with 72.3% of sensitivity and 79.0% of specificity. Conclusions The ICG-R15 level was associated with portal pressure in both patients with non-virus cirrhosis and patients with virus cirrhosis and predicts the incidence of PH with relatively good discriminatory ability. Clinical trial number https://clinicalTrials.gov(ID:NCT00827723) Local ethics committee number CER-VD 251.08

Background In preclinical models, recombinant human relaxin-2 (serelaxin) had anti-fibrotic effects and ameliorated portal hypertension (PH). A small exploratory study in patients with cirrhosis also suggested that serelaxin could reduce portal pressure. Methods In a phase 2, double-blind, randomised controlled study conducted in a single centre (Royal Infirmary of Edinburgh, UK), male and female adult participants with cirrhosis and clinically significant PH (CSPH; hepatic venous pressure gradient (HVPG) > 10 mmHg) were enrolled. Participants were allocated to serelaxin or placebo in a 3:1 ratio. The placebo was matched to serelaxin on appearance and administration protocol to create and maintain blinding. The primary endpoint was the change from baseline in fasting HVPG after 2 h of peripheral i.v. serelaxin infusion (80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min). Secondary endpoints included the change from baseline in hepatic blood flow and systemic haemodynamics (cardiac index, systemic vascular resistance index and aortic pulse wave velocity). Short-term safety and tolerability of serelaxin were assessed. Results A total of 17 participants were screened, 15 were randomised and 11 completed the study ( n  = 9 serelaxin, n  = 2 placebo). Reasons for withdrawal were baseline HVPG < 10 mmHg ( n  = 2) and technical failure ( n  = 2). The trial ended early due to manufacturer discontinuation of the study drug. The median age was 56 (range 43–69) years and 73% of participants were male. Alcohol was the commonest cirrhosis aetiology ( n  = 10). Participants had a median Model for End-Stage Liver Disease score of 10 (range 6–14). The mean baseline HVPG was 16.3 (range 10.3–21.7) mmHg. Individual responses were variable, but overall there was no statistically significant change in HVPG after 2 h of i.v. serelaxin (arithmetic mean of difference ± SD was 0.4 ± 3.5 mmHg (95% CI –2.3, 3.1; p  = 0.76)). There were also no substantial changes from baseline in hepatic or systemic haemodynamics. We recorded 12 adverse events in 7 participants treated with serelaxin; none were significant, and most were unrelated to the investigational medicinal product. There were no serious adverse events. Conclusion In a small randomised, phase 2, proof-of-concept study in patients with cirrhosis and CSPH, serelaxin infusion was safe and well-tolerated but had a neutral effect on HVPG. Trial registration ClinicalTrials.gov , NCT02669875. Registered on 1 February 2016.

Portal hypertension (PHT) is pivotal in managing decompensated cirrhosis. In clinical practice, hepatic venous collaterals are frequently present, often leading to failure or reduced accuracy of hepatic venous pressure gradient (HVPG) measurements, thereby making HVPG an imperfect surrogate for the portal pressure gradient (PPG). Artificial neural networks (ANNs) have shown potential in integrating multidimensional clinical variables and predicting complex disease states; however, their value in the assessment of PHT remains insufficiently validated. The study compared ANN-predicted PPG with measured PPG and HVPG in two cohorts: Group A (all patients), reflecting routine clinical practice, and Group B (excluding cases with coefficient of variation (CV) > 30%, most with venous collaterals), approximating optimized conditions. Subgroup analyses in Group B further assessed differences by etiology and Child–Pugh class. We retrospectively included 164 patients with decompensated cirrhosis who underwent TIPS between June 2014 and July 2024, with intra-procedural HVPG and PPG measurements. An ANN model predicted PPG based on INR, WBC, and portal vein diameter. Group A included all patients (n = 164), reflecting real-world conditions where HVPG may be affected by collaterals. Group B represented a strict quality-control cohort (n = 101), in which cases with a measurement CV > 30% were excluded; retrospective review indicated that most of these excluded patients exhibited hepatic venous collaterals thereby approximating an “ideal condition” without the influence of collaterals. Statistical analyses included paired t tests, Pearson correlations, Steiger’s Z-tests, and Bland–Altman analysis. Subgroup analyses were conducted by etiology and Child–Pugh class. In the overall cohort (Group A, n = 164), HVPG showed negligible correlation with PPG (r = 0.014), whereas ANN-predicted PPG demonstrated moderate correlation (r = 0.437, P  < 0.001) with significantly narrower LoA. In the quality-controlled cohort (Group B, n = 101), both HVPG and ANN-predicted PPG correlated moderately with PPG (r = 0.457 vs. 0.476) with comparable agreement. Subgroup analyses indicated that ANN outperformed HVPG in hepatitis B and Child–Pugh C patients, while HVPG was slightly better in alcohol-related cirrhosis; both methods performed poorly in autoimmune liver disease. HVPG remains the gold standard for assessing portal pressure but is limited by hepatic venous collaterals, advanced liver dysfunction, and the need for invasive measurement. ANN-predicted PPG showed favorable correlation and agreement with measured PPG, providing a noninvasive, simple, and reproducible complement to HVPG for clinical assessment and follow-up.