Etiologic factor removal (ER) drives recompensation and improves portal hypertension in cirrhosis. Esophageal varices (EV) and portosystemic shunts (PSS) have been found in patients despite hepatic venous pressure gradient (HVPG) dropping below 10 mmHg after ER, questioning HVPG accuracy in reflecting true portal pressure in the setting of ER. We aim to evaluate the correlation of HVPG with direct portal pressure (DPP) in patients with persistence of EV after ER despite HVPG <10 mmHg. This is a bicentric ‘proof of concept’ study evaluating HVPG and ultrasound-guided percutaneous DPP in patients with HCV or alcohol-related cirrhosis with persistent varices and HVPG <10 mmHg after at least 5 years of ER. Seven patients with HCV and three with alcohol-related cirrhosis with persistent varices and HVPG <10 mmHg after at least 5 years of ER were included. At evaluation, all patients had a patent portal vein and were compensated. The median platelet count was 129.5 (IQR 95–145) × 10⁹/ml, and the median liver stiffness measurement was 16.15 (IQR 14.4–22.3) kPa. In five patients, EV remained the same size (two large and three small), and five downsized to small after ER. Wedge hepatic vein pressure (median 19 [IQR 16.5–20] mmHg) and portal pressure (median 18 [IQR 15–19.5] mmHg) had an excellent correlation (R = 0.93, p <0.0001). Portal pressure gradient (PPG) confirmed the absence of clinically significant portal hypertension as identified by HVPG across all the patients. HVPG accurately reflects PPG in the context of HCV and alcohol-related cirrhosis regression. After ER, EV may persist despite HVPG <10 mmHg. The benefit of prophylaxis in patients with EV and HVPG <10 mmHg is unknown. Future studies with clinical endpoints are needed to validate our findings. Despite a favorable evolution after the removal of the etiologic factor, varices persist in some patients, and there is a lack of concise guidelines for the evaluation and management of portal hypertension in this population. Our research underscores the persistence of varices in the absence of clinically significant portal hypertension and significantly demonstrates the accuracy of hepatic venous pressure gradient (HVPG) in reflecting portal vein pressure in this specific patient group. These findings emphasize the crucial role of HVPG in the assessment of portal hypertension after etiologic factor removal and lay the groundwork for further investigation into clinical outcomes and the necessity of non-selective beta-blockers in individuals with persistent varices after the removal of etiologic factor.

Acute variceal bleeding in cirrhosis represents a critical clinical event that significantly impacts patient prognosis, with mortality rates increasing further after a second episode. This underscores the need for immediate intervention and optimal prophylaxis. The creation of a transjugular intrahepatic portosystemic shunt (TIPS) has been proven to be highly effective for managing esophageal variceal bleeding. However, the use of TIPS for managing cardiofundal gastric varices and ectopic varices remains debated due to their unique vascular anatomy and the limited data available. These varices, although less prevalent than esophageal varices, are complex and heterogeneous vascular shunts between the splanchnic venous system and the systemic veins. Indeed, while endoscopic therapy with tissue adhesives is widely endorsed for achieving hemostasis in active hemorrhage, there is no consensus regarding the optimal approach for secondary prophylaxis. Recent research emphasizes the efficacy of endovascular techniques over endoscopic treatments, such as TIPS and endovascular variceal embolization techniques. This review examines the use of TIPS in managing acute variceal bleeding in patients with cirrhosis, focusing specifically on cardiofundal gastric varices and ectopic varices, discussing optimal patient care based on the latest evidence, aiming to improve outcomes for this challenging subset of patients.

Continuous infusion of terlipressin may result in a more sustained reduction in portal pressure with fewer adverse effects than administered as a bolus. This study aimed to compare the hepatic and cardiopulmonary hemodynamic effects and safety profiles of bolus vs. terlipressin continuous infusion. This is a single-center, single-blinded, double-dummy, parallel-group, clinical trial in which 38 patients with cirrhosis and portal hypertension were randomized to receive the following: 1 mg bolus of terlipressin + continuous infusion of placebo (TERLBOL, n = 12), a bolus of placebo + continuous infusion of terlipressin (2 or 4 mg/day if <10% reduction in hepatic venous pressure gradient [HVPG] at 30 min of infusion) (TERLINF, n = 14), or a bolus of octreotide (50 μg) + continuous infusion of octreotide (50 μg/h) (OCTR, n = 12) as an additional control group. HVPG, cardiopulmonary pressures, and cardiac output were measured at baseline and after 30, 60, and 120 min. Sixty-eight percent of patients were male, with a median age of 59 years. There were no significant differences in baseline characteristics. In the TERLBOL group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.14). However, cardiopulmonary and mean arterial pressures significantly increased, whereas cardiac output and heart rate significantly decreased. In the TERLINF group, there were nonsignificant changes in cardiopulmonary hemodynamics or HVPG (NS) despite doubling the infusion dose after 30 min in 13/14 patients. In the OCTR group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.08), and pulmonary capillary pressure significantly decreased. All treatments were well tolerated, and no adverse events were observed. There were nonsignificant reductions in HVPG with the three therapeutic strategies. Further investigations are warranted to determine the optimal dosing strategy for continuous infusion of terlipressin in patients with cirrhosis and portal hypertension. The results of our study do not show a significant reduction in portal pressure, at least in the first 2 h after the selected dose. Although the study was not performed in the setting of acute variceal bleeding and terlipressin was used as a standard therapy, these results do not support the treatment strategy of terlipressin infusion alone at the doses studied for the management of acute variceal bleeding, where a quick reduction in portal pressure is thought to play a major role controlling variceal bleeding. It is important to highlight that the continuously infused terlipressin regimen is better tolerated and appears to have a better cardiopulmonary safety profile. Other treatment strategies of continuous terlipressin infusion, such as initial bolus administration or higher infusion doses, should be evaluated to support its use in managing variceal bleeding. EudraCT No. 2019-004328-39.

Background and Aims: Assessing liver congestion and portal hypertension (PHT) in Budd–Chiari syndrome (BCS) remains challenging. We evaluated liver and spleen stiffness measurements (LSM, SSM) obtained by transient elastography as non‐invasive tools for identifying clinically meaningful liver congestion in BCS. Methods: This retrospective study included consecutive patients with BCS followed at our unit. At each visit, patients were classified as having a controlled or uncontrolled clinical status based on clinical, biochemical, imaging and/or hemodynamic data, by absence or presence of clinically significant PHT. LSM and SSM were independently obtained at all visits and diagnostic performance for classifying clinical status was assessed using receiver operating characteristic (ROC) analysis. Results: Sixty‐six patients were included with a median follow‐up of 65.5 months (range:2–182): 34 had persistently controlled status, 11 persistently uncontrolled, 14 initially uncontrolled improved to sustained controlled status and 7 showed fluctuating status. Two‐hundred eighty‐nine LSM were obtained during periods of controlled clinical status (median:15. 1 kPa , IQR :10.9–19.9) and 203 during uncontrolled status (median: 41. 1 kPa , IQR : 34.8–64.5). LSM discriminated controlled from uncontrolled status ( AUC 0.985). LSM cut‐off of 25 kPa yielded 97.5% sensitivity, 92.5% specificity, 97.6% negative predictive value and 90% positive predictive value. SSM showed good discrimination ( AUC 0.854), with values ≤ 30 kPa ruling out and > 40 kPa ruling in uncontrolled status, but accuracy was inferior to LSM . LSM values rapidly decreased following liver congestion resolution after interventional procedures. Conclusions: In BCS, LSM shows excellent concordance with clinical status and periodic assessment may facilitate clinical management. SSM provides complementary information but does not outperform LSM.

Patients with non-cirrhotic non-tumoral portal venous system thrombosis (NCNT-PVT) require long-term anticoagulation to prevent rethrombosis (either splanchnic or at any site, referred to as overall rethrombosis - oRT) when there is an underlying high-risk thrombophilic disorder or history of previous thrombotic episodes. However, up to 25% of patients without such indications still develop oRT. Elevated factor VIII (≥150%), D-dimer (≥500 ng/ml) or the presence of high molecular risk (HMR) variants have been proposed as risk predictors for oRT in these patients. This study aimed to compare the prognostic value of these three biomarkers in a cohort of patients with NCNT-PVT. We performed a multicenter, retrospective, observational study including 123 patients with NCNT-PVT without an indication for long-term anticoagulation. During a median follow-up of 89.3 months (IQR 36-129), 33 patients (27%) developed venous oRT, with a cumulative incidence of 7%, 17% and 26% at 1, 5 and 10 years. Factor VIII ≥150% and HMR were associated with oRT risk (hazard ratio 5.92, 95% CI 2.67-13.15, p <0.01; and hazard ratio 2.07, 95% CI 1.01-4.24, p = 0.04, respectively) while D-dimer ≥500 ng/ml showed a non-significant trend. Multivariate analysis confirmed factor VIII and HMR as independent predictors. Patients with unprovoked or local factor-associated PVT have a clinically relevant long-term risk of recurrence, with a 25% cumulative incidence of oRT at 10 years. Elevated factor VIII (≥150%) identifies a subgroup at particularly increased risk, and its combination with HMR variants may further refine risk stratification. This study addresses an important clinical gap by evaluating whether prothrombotic and genetic biomarkers can help identify patients with non-cirrhotic, non-tumoral portal vein thrombosis who remain at risk of recurrent thrombosis despite the absence of classical thrombophilia. Our results show that persistently elevated factor VIII levels, alone or combined with high molecular risk variants, are strong predictors of rethrombosis in this population. These findings may help refine recurrence-risk stratification in patients traditionally considered low risk and could support more individualized decisions regarding long-term anticoagulation and follow-up intensity.