Significant Portal Hypertension Research Articles

Endoscopic ultrasound‐guided portal pressure gradient identifies patients with previously undiagnosed clinically significant portal hypertension

AbstractAimsPortal hypertension (PH) is a complication of cirrhosis that leads to hepatic decompensation. Assessing the portal pressure gradient (PPG) provides valuable information for disease assessment, staging, and prognosis. In this study, we aimed to report the utilization of endoscopic ultrasound (EUS)‐guided PPG (EUS‐PPG) measurements in a real‐world setting.MethodsThis retrospective analysis included patients at a tertiary care center who underwent EUS‐PPG between February 2021 and May 2022. The most common indication was to establish or exclude the diagnosis of cirrhosis, followed by an assessment of surgical risk in the setting of suspected cirrhosis. Extensive demographic and clinical data were collected, and statistical analysis was performed using the Student's t test.ResultsEighteen patients underwent EUS‐PPG. Technical success was achieved in 17 of the 18 patients. No complications were observed. The mean scores of Child‐Pugh, Model for End‐Stage Liver Disease‐Sodium, and Fibrosis‐4 scores were 5.1 ± 0.5, 9.0 ± 3.0, and 3.7 ± 4.5, respectively. Of the 18 patients, two presented with esophageal varices and six with portal hypertensive gastropathy. The mean PPG was 5.8 ± 4.5 mmHg, and five patients exhibited clinically significant PH (CSPH). Of the 18 patients, 15 underwent concurrent EUS‐liver biopsy, which was 100% successful and provided diagnostic histology for all patients. The PPG data led to changes in the clinical management of 17 patients.ConclusionsEUS‐PPG is safe and technically feasible. The Child‐Pugh score did not correlate well with the presence of CSPH; however, PPG measurements resulted in changes in the management of almost all patients. Larger studies correlating EUS‐PPG with other assessments of liver diseases are required.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10mmHg. A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15kPa and platelet count ≥ 150 × 109/L] OR SSM < 21kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25kPa OR SSM ≥ 50kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Distribution of Normative Percentiles of Liver Stiffness Measurement Using Ultrasound Shear Wave Elastography in an Adult Asian Indian Population

Abstract Objective The aim of this study was to determine the normative percentiles for liver stiffness measurement (LSM) using shear wave elastography in an adult Asian Indian population as part of the preventive radiology initiative of the Indian Radiological and Imaging Association (IRIA). Methods LSMs were ascertained by two-dimensional (2D) shear wave elastography using the Mindray Resona series of ultrasound machines. The image quality was assessed using the motion stability index (M-STB) and reliability (RLB) map. Ten acquisitions were documented, and an interquartile range-to-median (IQR/M) ratio ≤30% kilopascal (kPa) units was considered a good-quality measurement. A subgroup of the study population without comorbidities was chosen to derive the normative percentile distribution of LSM using a generalized least squares multivariable fractional polynomial regression model that adjusted for sex and body mass index (BMI). The effectiveness of the estimated percentiles was assessed on the entire study population using the greater than 90th percentile value of the LSM as the cutoff for abnormality. Results The study included 852 people who underwent shear wave elastography from June 2022 to July 2023. The magnitude of compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) was 6.81% (95% confidence interval [CI]: 5.30–8.7) and 4.91% (95% CI: 3.67–6.60), respectively. The normative percentiles were estimated from 282 persons without associated comorbidity and risk factors. The mean age (standard deviation [SD]) of the normal individuals was 40.90 ± 12.92 years, and 210 (71.47%) were males. The mean age (SD) of the 570 persons excluded from the normative percentiles analysis was 47.94 (12.49) years and 72.11% were males. The sex- and BMI-adjusted age-specific 90th percentiles of LSM were 8.76, 8.78, 8.96, 8.97, 9.25, and 9.45 kPa for 18 to 20, 21 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years, respectively. Conclusion The sex- and BMI-adjusted age-specific 90th percentiles for LSM using shear wave elastography in Asian Indian adults are almost similar to the greater than 9 kPa cutoff proposed by the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement guidelines to discriminate cACLD and CSPH from normal individuals.

Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous–portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension.

Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD). Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups. We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH. We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.

Review article: Recent advances in ascites and acute kidney injury management in cirrhosis.

Better understanding of disease pathophysiology has led to advances in managing ascites and its associated complications including hepatorenal syndrome-acute kidney Injury (HRS-AKI), especially medicinal and interventional advances. To review the latest changes in the management of ascites and HRS-AKI. A literature search was conducted in Pubmed, using the keywords cirrhosis, ascites, renal dysfunction, acute kidney injury, hepatorenal syndrome, beta-blockers, albumin, TIPS and vasoconstrictors, including only publications in English. The medicinal advances include earlier treatment of clinically significant portal hypertension to delay the onset of ascites and the use of human albumin solution to attenuate systemic inflammation thus improving the haemodynamic changes associated with cirrhosis. Furthermore, new classes of drugs such as sodium glucose co-transporter 2 are being investigated for use in patients with cirrhosis and ascites. For HRS-AKI management, newer pharmacological agents such as vasopressin partial agonists and relaxin are being studied. Interventional advances include the refinement of TIPS technique and patient selection to improve outcomes in patients with refractory ascites. The development of the alfa pump system and the study of outcomes associated with the use of long-term palliative abdominal drain will also serve to improve the quality of life in patients with refractory ascites. New treatment strategies emerged from better understanding of the pathophysiology of ascites and HRS-AKI have shown improved prognosis in these patients. The future will see many of these approaches confirmed in large multi-centre clinical trials with the aim to benefit the patients with ascites and HRS-AKI.

Four-dimensional flow magnetic resonance imaging for noninvasive diagnosis of clinically significant portal hypertension and high-risk gastroesophageal varices in patients with cirrhosis

IntroductionNoninvasive diagnoses of clinically significant portal hypertension (CSPH) and high-risk gastroesophageal varices are clinically relevant but challenging. Four-dimensional (4D) flow magnetic resonance imaging (MRI) provides comprehensive flow information and is a promising alternative. This study evaluated the efficacy of 4D flow MRI as a noninvasive method for diagnosing CSPH and high-risk varices in patients with liver cirrhosis. MethodsThis prospective study enrolled consecutive patients diagnosed with liver cirrhosis at a tertiary referral center between October 2020 and March 2021. Each participant underwent abdominal 4D flow MRI. Hemodynamic parameters within the portal vein, including the average and peak flow velocities, normalized flow volume (Qnormal), and regurgitant fraction (R%), were extracted and compared between healthy individuals and patients with CSPH and between participants with high- and low-risk varices. Subsequently, these parameters were incorporated into a logistic regression (LR) model refined using L1 regularization and validated using five-fold cross-validation. The diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. ResultsEighty-two participants were enrolled (71 patients diagnosed with liver cirrhosis and 11 healthy individuals serving as controls). Among hemodynamic parameters, patients with CSPH exhibited a notable increase in Qnormal of 0.66 ​± ​0.19 ​ml∗m2/[cycle∗kg] (P ​= ​0.001) and an R% of 1.98 (2.05) (P ​= ​0.002). Similarly, patients with high-risk varices showed a higher Qnormal of 0.61 ​± ​0.15 ​ml∗m2/[cycle∗kg] (P ​< ​0.001) and R% of 1.88 (2.81) (P ​= ​0.006). ROC analysis revealed an area under the curve (AUC) for Qnormal of 0.93 and 0.91 for R% for diagnosing CSPH, while the LR model showcased a superior AUC of 0.95. For high-risk varices, Qnormal and R% showed AUC values of 0.75 and 0.70, respectively, whereas the LR model showed a higher AUC of 0.84. ConclusionAs a noninvasive imaging modality, 4D flow MRI exhibits considerable potential for the diagnosis of CSPH and high-risk gastroesophageal varices; thus, it may minimize the reliance on invasive procedures in patients with cirrhosis.

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

Non-invasive liver disease assessment to identify portal hypertension: A systematic review supporting the AASLD Practice Guideline.

Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. Hepatic venous pressure gradient (HVPG), a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and by its availability, non-invasive liver disease assessments (NILDAs) to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. We conducted a systematic review of Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22nd, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies which compared non-invasive tests (blood, and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥10mm Hg) in patients with chronic liver disease (this therefore limited the number of studies that could be included). Outcomes reported included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2,492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood based tests, including aspartate to platelet ratio index (APRI) (56% sensitivity and 68% specificity) and fibrosis-4 (FIB-4) (54% sensitivity and 73% specificity) had low accuracy measures. Imaging based tests (transient elastography (TE) and shear wave elastography detection of liver stiffness (LSM)) had better accuracy, but also had substantial variation; at 15kPa, TE sensitivity was 90%-96% and specificity was 48%-50% while at 25kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging based tests are the best available NILDA to detect CSPH, CSPH is highly unlikely to be present at an LSM ≤15kPa and likely to be present at an LSM ≥25kPa. While imaging-based NILDA appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the SR. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

Carvedilol has emerged as the preferred β-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Machine Learning-Based Assessment of Survival and Risk Factors in Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma for Optimized Patient Management.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients.

The Usefulness of Non-Invasive Liver Stiffness Measurements by Fibroscan in Predicting Clinically Significant Portal Hypertension in Cirrhotic Patients

Background: Liver stiffness measurement (LSM) has proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. The aim of our study is to investigate if LSM could predict the size of Esophageal varices (EV) in patients with liver cirrhosis to limit upper endoscopic procedures only to those patients that really need it (patients with large EV or EV at risk for bleeding). Methods: Our retrospective study includes 46 cirrhotic patients over a period of 40 months between January 2019 and April 2022, at the Service of Digestive Functional Explorations of Hepato-gastroenterology of the University hospital Ibn-Sina of RABAT, all patients underwent a liver stiffness measurement by Transient elastography FibroScan. Results: Of the 46 cirrhotic patients included in this study, with a mean age of 58.5(21-90) years, 18 (39.1%) of patients were male and 28(60.9%) were female. the predominant etiology of cirrhosis was chronic viral hepatitis C 20 (43.5%). The area under the ROC curve of the diagnosis of large EVs (EV≥II) was 0.724 (95%CI). The optimal cut-off of elasticity was 20.5 for this purpose, with a sensitivity of 66.7%, specificity of 94.74%. Conclusions: these results indicate that Transient elastography FibroScan is a reliable, non-invasive method to assess portal hypertension and can be used for the screening and diagnosis of clinically significant portal hypertension.

Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

Simple blood tests to diagnose compensated advanced chronic liver disease and stratify the risk of clinically significant portal hypertension.

Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. The limited availability of liver stiffness measurements (LSM) impedes the identification of patients at risk for cACLD/CSPH outside of specialized clinics. We aimed to develop a blood-based algorithm to identify cACLD by fibrosis-4 (FIB-4) and CSPH by von Willebrand factor/platelet count ratio (VITRO). Patients with (suspected) compensated chronic liver disease undergoing FIB-4+LSM were included in the LSM/FIB-4 cohorts from Vienna and Salzburg. The HVPG/VITRO cohorts included patients undergoing HVPG-measurement + VITRO from Vienna and Bern.LSM/FIB-4-derivation-cohort: We included 6143 patients, of whom 211 (3.4%) developed hepatic decompensation. In all, 1724 (28.1%) had LSM ≥ 10 kPa, which corresponded to FIB-4 ≥ 1.75. Importantly, both LSM (AUROC:0.897 [95% CI:0.865-0.929]) and FIB-4 (AUROC:0.914 [95% CI:0.885-0.944]) were similarly accurate in predicting hepatic decompensation within 3 years. FIB-4 ≥ 1.75 identified patients at risk for first hepatic decompensation (5 y-cumulative incidence:7.6%), while in those <1.75, the risk was negligible (0.3%).HVPG/VITRO-derivation cohort: 247 patients of whom 202 had cACLD/FIB-4 ≥ 1.75 were included. VITRO exhibited an excellent diagnostic performance for CSPH (AUROC:0.889 [95% CI:0.844-0.934]), similar to LSM (AUROC:0.856 [95% CI:0.801-0.910], p = 0.351) and the ANTICIPATE model (AUROC:0.910 [95% CI:0.869-0.952], p = 0.498). VITRO < 1.0/ ≥ 2.5 ruled-out (sensitivity:100.0%)/ruled-in (specificity:92.4%) CSPH. The diagnostic performance was comparable to the Baveno-VII criteria.LSM/FIB-4-derivation cohort findings were externally validated in n = 1560 patients, while HVPG/VITRO-derivation-cohort findings were internally (n = 133) and externally (n = 55) validated. Simple, broadly available laboratory tests (FIB-4/VITRO) facilitate cACLD detection and CSPH risk stratification in patients with (suspected) liver disease. This blood-based approach is applicable outside of specialized clinics and may promote early intervention.

Validation of Baveno VII criteria and other non-invasive diagnostic algorithms for clinically significant portal hypertension in hepatitis delta

Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. Patients with HDV-cACLD (LSM ≥10kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. Fifty-one patients (HVPG ≥10mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p < 0.001), VITRO (n= 31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p < 0.001), and SSM (n= 20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p < 0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII 'grey zone' (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options.

Protocolo diagnóstico de la hepatopatía crónica

Chronic liver disease is usually paucisymptomatic until the complications of liver failure and/or portal hypertension appear. In most cases, the diagnostic suspicion usually begins with abnormalities on the liver profile and/or a finding on imaging tests. The etiological diagnosis is broad, with the most frequent causes being metabolic dysfunction-associated liver disease, viral liver disease, and alcohol-related liver disease. A medical history and physical examination are the basis for guiding the diagnostic process, which must be supported by additional analytical and radiological tests. This etiologic evaluation must always be performed alongside an assessment of liver disease severity through an estimation of the degree of fibrosis and the presence of clinically significant portal hypertension. Currently, both of these are preferably estimated in a non-invasive manner. This protocol aims to summarize the fundamental keys to the diagnostic process in the case of suspected chronic liver disease.

Drug treatment of portal hypertension - Current approaches

AbstractIn western industrialized nations, liver cirrhosis is the most common cause of portal hypertension. Portal hypertension is defined by a persistent increase in portal pressure &gt;7mmHg. An HVPG &gt;10mmHg defines the presence of clinically significant portal hypertension. The presence of clinically significant portal hypertension (CSPH) in patients with liver cirrhosis is a key risk factor for the transition from a compensated to a decompensated stage of the disease. CPSH can be determined invasively by measuring HPVG or noninvasively by measuring liver stiffness, platelet count and spleen stiffness. If acute decompensation manifests itself (e.g. ascites, esophageal variceal bleeding), this is associated with a significant increase in patient morbidity and mortality. Non-selective beta blockers (NSBB) are the standard medical therapy for portal hypertension in the presence of CSPH. Due to the additional α1-antiadrenergic effects, carvedilol leads to a greater reduction in portal pressure compared to traditional NSBB (e.g. Propanolol). In patients with compensated liver cirrhosis, carvedilol is better than traditional NSBB at reducing the risk of variceal bleeding and the occurrence of hepatic decompensation. The early identification of CSPH and evaluation of drug therapy to reduce portal hypertension is therefore crucial to improve the prognosis of patients.

A223 DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS AT THE OTTAWA HOSPITAL

Abstract Background Primary sclerosing cholangitis (PSC) is present in up to 8% of individuals with inflammatory bowel disease (IBD). Characteristics of this population are unique and data are limited. Aims To describe the demographic and clinical characteristics of all individuals with PSC-IBD managed at The Ottawa Hospital (TOH). Methods A chart review was performed for 132 patients with PSC-IBD followed at TOH between January 1998 and July 2023. Results Of 132 individuals with PSC-IBD identified at TOH, 26.5% had Crohn’s disease (CD), 68.2% had ulcerative colitis (UC) and 5.3% had IBD-unclassified. Median age at diagnosis were 25.3 (IQR 20.94) for IBD and 33.84 (IQR 23.98) for PSC, and 66.7% of all patients were male. More than 17% had a co-morbid autoimmune disease other than IBD or PSC. Of those with CD, roughly 15% had fibrostenotic or penetrating complications and 17% had perianal disease at the time of IBD diagnosis. Only 28% ever had a liver biopsy, whereas the majority were diagnosed with PSC by cholangiography. PSC distribution was isolated intrahepatic in 47%, isolated extra-hepatic in 5.1% and mixed intra/extra-hepatic in 38.5%. Clinically significant portal hypertension was present in 11.5% at PSC diagnosis, while 27.3% and 16.7% developed cirrhosis and liver decompensation, respectively by last follow-up. 17.4% underwent liver transplant, of which 30.4% developed PSC recurrence post-transplant. Conclusions Our study showed that the majority of PSC-IBD patients are young males with UC. Co-morbid autoimmune diseases are common while isolated extra-hepatic PSC is uncommon. Cirrhosis, liver decompensation and liver transplant are frequent occurrences in this population. PSC recurrence post-transplant is observed in more than 30% of patients. Funding Agencies None

Innovations in endoscopic ultrasound for portal hypertension and its role in managing complications in clinical practice: Lessons learned from a tertiary referral public hospital

AbstractPortal hypertension (PH) poses significant challenges. This paper presents an innovative study on the utilization of endoscopic ultrasound (EUS) for both the diagnosis and management of PH. Conducted at Dr. Cipto Mangunkusumo National General Hospital in Jakarta, this retrospective case series included patients diagnosed with PH through clinical examination, imaging evaluation, and esophagogastroduodenoscopy. Exclusion criteria comprised a history of reduced blood consumption within the last 5 days, hepatocellular carcinoma, massive ascites, or elevated international normalized ratio (&gt;1.4). EUS‐guided portal pressure gradient (PPG) measurements were performed using an innovative standard manometer. The study involved 15 patients, with 14 having liver cirrhosis and 1 diagnosed with Budd–Chiari syndrome. Among them, nine patients experienced bleeding due to gastroesophageal varices. Small and large esophageal varices were identified in four and eight patients, respectively. Gastroesophageal varices type 1 were observed in two patients, and type 2 in four patients. Isolated gastric fundal varices type 1 were present in one patient. Based on EUS‐PPG measurements, 14 patients exhibited clinically significant portal hypertension. Seven patients underwent endoscopic band ligation and three underwent EUS‐guided cyanoacrylate injection during the same session as the EUS‐PPG measurement procedure. Notably, no adverse events, such as abdominal pain, perforation, or bleeding were observed during or after the procedure. EUS emerges as a promising and accurate tool for both diagnosis and management.

Non-selective beta-blockers lower the risk of first decompensation in patients with cirrhosis and enduring clinically significant portal hypertension after etiological treatment

Non-selective beta-blockers lower the risk of first decompensation in patients with cirrhosis and enduring clinically significant portal hypertension after etiological treatment