Esophageal varices are life-threatening complications in which the enlargement of the esophageal veins causes bleeding and reduces blood flow to the esophagus. They are complications caused by portal hypertension, renal failure, hepatic dysfunction, and infection. The leading cause of esophageal varices is cirrhosis, as patients with this disease are more susceptible to forming esophageal varices. Bleeding episodes occur due to the rupture of the blood vessels. We present the case of a 45-year-old male patient in the hospital with a history of chronic alcohol use and clinical symptoms of hematemesis, a distended abdomen, and melena. The patient experienced mild symptoms of giddiness and dizziness after undergoing various radiological investigations, laboratory tests, ultrasonography (USG), and CT scans. USG diagnosed portal hypertension, gross ascites, pleural effusion, and hepatosplenomegaly. A CT scan diagnosed the patient with esophageal varices and testicular carcinoma. Laboratory tests diagnosed anemia. The treatment plan included oral and intravenous iron supplements, blood transfusions, vitamin B12, folate supplements, and nonselective beta-blockers to manage portal hypertension and reduce variceal bleeding risk. During acute bleeding episodes, vasoconstrictors and endoscopic band ligation were employed. Regular endoscopies and hepatic venous catheterization were conducted to monitor and manage the condition. Follow-up included regular assessments of hemoglobin levels, iron status, liver function tests, and periodic endoscopies. The patient\'s adherence to beta-blockers was closely monitored. Esophageal varices, often resulting from portal hypertension because of cirrhosis, require early diagnosis and a combination of pharmacological and endoscopic treatments to prevent complications. Advances in treatment have reduced mortality rates, but effective management of portal hypertension and liver dysfunction remains crucial.

UNASSIGNED: EUS-guided portal pressure gradient (PPG) is a novel technique that permits a true, direct measure of portal vein pressure and hepatic vein pressure. This article details our experience and lessons learned from 20 consecutive outpatient EUS-PPG procedures performed at a single center, along with simultaneous EUS-guided liver biopsy, variceal screening, and variceal banding.
UNASSIGNED: Data on the first 20 patients who underwent EUS-PPG at a single center were retrospectively viewed and analyzed. The effects of various liver diseases or other patient-related factors on the clinical and technical success of EUS-PPG measurements, as well as EUS-guided liver biopsy (EUS-LB), were evaluated. During the procedure, if esophageal varices were encountered, they were assessed, and if felt to be clinically indicated, endoscopic variceal ligation was performed.
UNASSIGNED: The 20 patients included 10 male and 10 female patients. All procedures were technically successful. In all patients, the portal vein and hepatic veins could be easily identified. One adverse event of bleeding occurred during the EUS-PPG measuring procedure. All 20 EUS-LBs were technically successful and yielded adequate samples for histological evaluations, with an average of 25 complete portal tracts per sample. Among patients with esophageal varices, 40% of patients underwent banding. The mean EUS-PPG among 5 patients with esophageal varices was 11.6 mm Hg, compared with 3.2 mm Hg among 15 patients without esophageal varices.
UNASSIGNED: This study demonstrates that EUS-PPG is a novel, safe, reproducible, and effective technique. Also, the fact that EUS-PPG, EUS-LB, variceal screening, and variceal banding could be performed in 1 session and on an outpatient basis speaks to the growing relevance and impact of the nascent field of endohepatology.

Managing complications of liver cirrhosis such as varices needing treatment (VNT) and clinically significant portal hypertension (CSPH) demands precise and non-invasive diagnostic methods. This study assesses the efficacy of spleen stiffness measurement (SSM) using a 100-Hz probe for predicting VNT and CSPH, aiming to refine diagnostic thresholds. A retrospective analysis was conducted on 257 cirrhotic patients, comparing the diagnostic performance of SSM against traditional criteria, including Baveno VII, for predicting VNT and CSPH. The DeLong test was used for statistical comparisons among predictive models. The success rate of SSM@100 Hz was 94.60%, and factors related to SSM failure were high body mass index and small spleen volume or length. In our cohort, the identified SSM cut-off of 38.9 kPa, which achieved a sensitivity of 92% and a negative predictive value (NPV) of 98% for detecting VNT, is clinically nearly identical to the established Baveno threshold of 40 kPa. The predictive capability of the SSM-based model for VNT was superior to the LSM ± PLT model (p = 0.017). For CSPH prediction, the SSM model notably outperformed existing non-invasive tests (NITs), with an AUC improvement and significant correlations with HVPG measurements (obtained from 49 patients), highlighting a correlation coefficient of 0.486 (p < 0.001) between SSM and HVPG. Therefore, incorporating SSM into clinical practice significantly enhances the prediction accuracy for both VNT and CSPH in cirrhosis patients, mainly due to the high correlation between SSM and HVPG. SSM@100 Hz can offer valuable clinical assistance in avoiding unnecessary endoscopy in these patients.

UNASSIGNED: Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown.
UNASSIGNED: In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes.
UNASSIGNED: Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion (p < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four (N = 42, 9.5%) patients at 6-12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively.
UNASSIGNED: Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation.

UNASSIGNED: To evaluate the role of hepatic venous pressure gradient (HVPG) measurement in patients with resectable hepatocellular carcinoma (HCC) we describe our experience with the procedure as part of our hospital standard preoperative algorithm. We present our protocol for this situation, the HVPG measurement procedure, and the results of our cohort.
UNASSIGNED: We performed a retrospective statistical analysis of all patients who underwent planned hepatic resection for HCC with HVPG measurement between 1/2016 and 1/2023. The cohort included 35 patients (30 males, mean age 69.5 years) who underwent HVPG measurement before liver resection for HCC.
UNASSIGNED: The success rate of measurement was 91.4%, with serious complications in 2.9% of cases. Due to the clinically significant portal hypertension (CSPH) 31.3% of patients were rejected for resection. Seventeen patients with excluded CSPH underwent resection with one case of a postoperative liver event, liver decompensation, representing 5.9% of them. One patient (5.9%) had a complicated postoperative course with fasciitis. None of the patients who underwent resection (88.2%) was readmitted to the hospital due to surgical complications or a liver event during 90 days of follow-up, and no death was reported. The median overall survival (OS) in the resected subgroup was 70 months (95% CI: 52-86), and in patients rejected for surgery (resection and transplantation) 35 months (95% CI: 13-48).
UNASSIGNED: HVPG measurement is the gold standard for the quantification of portal hypertension. Hepatic vein catheterization is invasive, but a safe procedure, with a clear impact on the management of resectable HCC.

UNASSIGNED: Limited data exist on strategies other than hepatic venous pressure gradient (HVPG) estimation to predict future events in patients with cirrhosis presenting with variceal bleed (VB) but are otherwise compensated. We assessed whether liver stiffness measurement (LSM) during VB episode could accurately predict this risk.
UNASSIGNED: Consecutive patients with cirrhosis with VB as their index decompensation event underwent HVPG and LSM estimation during the VB episode in this prospective study. New onset further decompensation events (ascites, VB, encephalopathy) was assessed over follow-up. The performance characteristics of postbleed LSM were compared with model for end stage liver disease (MELD) score and HVPG to predict future decompensation and were cross-validated.
UNASSIGNED: Mean age of the cohort (n = 68) was 44.2 years and alcohol-related liver disease (55.9%) was the most common etiology. Over a median follow-up of 14 (9-18) months, 18(26.4%) patients developed further decompensation with ascites being the most common event. Patients with further decompensation had a higher median postbleed LSM [60.5 kPa (53-70) vs. 25 kPa (18-34), P < 0.001], HVPG [ 19 mm Hg vs. 16 mmHg, P = 0.005], and MELD score [ 12.5 (11-14.7) vs. 10 (8-12) P < 0.001]. The area under receiver-operator characteristics curve for postbleed LSM [0.928 (95%CI: 0.868-0.988)] was higher than both HVPG [0.733(0.601-0.865), P = 0.003] and MELD score [0.776(0.664-0.889), P = 0.019] to predict further decompensation. Optimism-corrected c-statistic using MELD and postbleed LSM was similar to a combination of HVPG, MELD, and postbleed LSM.
UNASSIGNED: Postbleed LSM is comparable to HVPG estimation in predicting further decompensation events in patients with otherwise compensated cirrhosis presenting with VB.

BACKGROUND: The role of hepatic venous pressure gradient (HVPG) in predicting further decompensation in cirrhosis patients with acute variceal bleeding (AVB) is not known. We aimed to evaluate the role of HVPG in predicting further decompensation in cirrhosis patients with AVB Methods: In this prospective study, 145 patients with cirrhosis with esophageal or gastric AVB were included. HVPG was measured on the day of the AVB. Decompensating events occurring after 42-days of AVB were considered further decompensation.
RESULTS: The median age of the study cohort was 44 years; 88.3% males. The predominant etiology of cirrhosis was alcohol (46.2%). Overall, 40 (27.6%) patients developed further decompensation during median follow-up of 296 days following AVB. Gastro intestinal bleeding n = 27 (18.6%) and new-onset/worsening ascites n = 20 (13.8%) were the most common decompensating events. According to the multivariate model, HVPG was an independent predictor of any further decompensation in esophageal AVB patients but not in gastric variceal bleeding patients. HVPG cut-off of ≥16 mmHg predicted further decompensation in the esophageal AVB. However, HVPG was not an independent predictor of mortality.
CONCLUSIONS: HVPG measured during an episode of acute variceal hemorrhage from esophageal varices predicts further decompensating events in cirrhosis patients.

Cirrhosis transcends various progressive stages from compensation to decompensation driven by the severity of portal hypertension. The downstream effect of increasing portal hypertension severity leads to various pathophysiological pathways, which result in the cardinal complications of cirrhosis, including ascites, variceal hemorrhage, and hepatic encephalopathy. Additionally, the severity of portal hypertension is the central driver for further advanced complications of hyperdynamic circulation, hepatorenal syndrome, and cirrhotic cardiomyopathy. The management of these individual complications has specific nuances which have undergone significant developments. In contrast to the classical natural history of cirrhosis and its complications which follows an insidious trajectory, acute-on-chronic failure (ACLF) leads to a rapidly downhill course with high short-term mortality unless intervened at the early stages. The management of ACLF involves specific interventions, which have quickly evolved in recent years. In this review, we focus on complications of portal hypertension and delve into an approach toward ACLF.

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.

UNASSIGNED: Portal hypertension (PH) is a frequent and severe clinical syndrome associated with chronic liver disease. Considering the mechanobiological effects of hydrostatic pressure and shear stress on endothelial cells, we hypothesised that PH might influence the phenotype of liver sinusoidal endothelial cells (LSECs) during disease progression. The aim of this study was to investigate the effects of increased hydrodynamic pressure on LSECs and to identify endothelial-derived biomarkers of PH.
UNASSIGNED: Primary LSECs were cultured under normal or increased hydrodynamic pressure within a pathophysiological range (1 vs. 12 mmHg) using a microfluidic liver-on-a-chip device. RNA sequencing was used to identify pressure-sensitive genes, which were validated in liver biopsies from two independent cohorts of patients with chronic liver disease with PH (n = 73) and participants without PH (n = 23). Biomarker discovery was performed in two additional independent cohorts of 104 patients with PH and 18 patients without PH.
UNASSIGNED: Transcriptomic analysis revealed marked deleterious effect of pathological pressure in LSECs and identified chromobox 7 (CBX7) as a key transcription factor diminished by pressure. Hepatic CBX7 downregulation was validated in patients with PH and significantly correlated with hepatic venous pressure gradient. MicroRNA 181a-5p was identified as pressure-induced upstream regulator of CBX7. Two downstream targets inhibited by CBX7, namely, E-cadherin (ECAD) and serine protease inhibitor Kazal-type 1 (SPINK1), were found increased in the bloodstream of patients with PH and were highly predictive of PH and clinically significant PH.
UNASSIGNED: We characterise the detrimental effects of increased hydrodynamic pressure on the sinusoidal endothelium, identify CBX7 as a pressure-sensitive transcription factor, and propose the combination of two of its reported products as biomarkers of PH.
UNASSIGNED: Increased pressure in the portal venous system that typically occurs during chronic liver disease (called portal hypertension) is one of the main drivers of related clinical complications, which are linked to a higher risk of death. In this study, we found that pathological pressure has a harmful effect on liver sinusoidal endothelial cells and identified CBX7 as a key protein involved in this process. CBX7 regulates the expression of E-cadherin and SPINK1, and consequently, measuring these proteins in the blood of patients with chronic liver disease allows the prediction of portal hypertension and clinically significant portal hypertension.