Portal Hypertension In Patients Research Articles

A 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system applied to predict postsplenectomy hemodynamic metrics.

Splenectomy is a common surgery for portal hypertensive patients with splenomegaly. Although splenectomy is able to effectively relieve the complications of portal hypertension, it also increases the risk of portal venous system thrombosis remarkably. Previous studies demonstrated that the hemodynamic metrics of the portal venous system could be employed in predicting the risk of postsplenectomy thrombosis, and 3D models were utilized to simulate the blood flow in the portal venous system. Aiming to reflect the global effect of splenectomy and better simulate the hemodynamic metrics, in this study, a 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system was constructed based on population-averaged data in combination with patient-specific preoperative clinical measurements. The pre- and postoperative global blood flows as well as the variations were calculated successfully, and the flow field and time-averaged wall shear stress of the portal venous system were simulated. The model-simulated spatial distributions of the hemodynamic metrics in the portal venous system were comparable with the regions suffering from thrombosis after splenectomy. These results imply that the present model could reflect the reallocation of the blood flow in the splanchnic circulation after splenectomy and simulate the hemodynamic metrics of the portal venous system, which would promote the more accurate risk stratification of postsplenectomy thrombosis and improve the patient-specific postoperative management.Clinical Relevance- The computational model developed by the present study provides a feasible scheme for simulating postsplenectomy hemodynamic metrics of the portal venous system more accurately, which would benefit the risk prediction and prophylaxis of portal venous system thrombosis for portal hypertensive patients receiving splenectomy.

Decreased Platelet Aggregation in Patients with Decompensated Liver Cirrhosis and TIPS Implantation.

Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective treatment of portal hypertension in patients with decompensated liver cirrhosis. However, some patients develop TIPS thrombosis with recurrence of portal hypertension. The role of platelets in TIPS thrombosis and the necessity of antiplatelet therapy is unclear. Therefore, we aimed to study platelet function in patients with liver cirrhosis prior to and after TIPS implantation. Platelet aggregation was tested in peripheral and portal-vein blood patient samples on the day (D) of TIPS implantation (D0), D4 and D30 following the procedure (platelet count above 100 × 103/µL, aspirin starting on D5) using whole-blood impedance aggregometry (WBIA) and light transmission aggregometry (LTA). In addition, surface platelet activation markers (P-selectin, activated GPIIb/IIIa) and platelet-neutrophil complexes (PNCs) were assessed by flow cytometry. Thrombin receptor activating peptide 6 (TRAP-6), adenosine diphosphate (ADP) and arachidonic acid (AA) were used as agonists. Healthy subjects were included as controls. Agonist-induced platelet aggregation was reduced (WBIA: TRAP-6 p < 0.01, ADP p < 0.01, AA p < 0.001; LTA: TRAP-6 p = 0.13, ADP p = 0.05, AA p < 0.01) in patients (D0, n = 13) compared with healthy subjects (n = 9). While surface activation markers at baseline were negligibly low, the percentage of PNCs was higher in patients than in controls (p < 0.05). ADP-induced P-selectin expression was increased (p < 0.001), whereas TRAP-6-induced GPIIb/IIIa activation was impaired (p < 0.001) in patients versus controls. PNC formation in response to agonists was not different between groups. Results did not differ between peripheral and portal-vein blood of patients (D0, n = 11) and did not change over time (D0, D4, D30) following TIPS implantation (n = 9). In summary, patients with decompensated liver cirrhosis display in vitro platelet aggregation defects in response to various agonists. Defective aggregation persists upon TIPS implantation. Therefore, we conclude that antiplatelet treatment to prevent TIPS thrombosis is questionable.

Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis

The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting. In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 109 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 109 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 109 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164. Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I2<25%) for most estimates. Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective β-blocker treatment. None.

Unconventional shunt surgery for non-cirrhotic portal hypertension in patients not suitable for proximal splenorenal shunt.

Proximal splenorenal shunt (PSRS) is a commonly performed procedure to decompress portal hypertension, in patients with refractory variceal bleed, especially in non-cirrhotic portal hypertension (NCPH). If conventional methods are hindered by any technical or pathological factors, alternative surgical techniques may be required. This study analyzes the effectiveness of various unconventional shunt surgeries performed for NCPH. A retrospective analysis of NCPH patients who underwent unconventional shunt surgeries during the period July 2011 to June 2022 was conducted. All patients were followed up for a minimum of 12 months with doppler study of the shunt to assess shunt patency, and upper gastrointestinal endoscopy to evaluate the regression of varices. During the study period, 130 patients underwent shunt surgery; among these, 31 underwent unconventional shunts (splenoadrenal shunt [SAS], 12; interposition mesocaval shunt [iMCS], 8; interposition PSRS [iPSRS], 6; jejunal vein-cava shunt [JCS], 3; left gastroepiploic-renal shunt [LGERS], 2). The main indications for unconventional shunts were left renal vein aberration (SAS, 8/12), splenic vein narrowing (iMCS, 5/8), portalhypertensive vascular changes (iPSRS, 6/6), and portomesenteric thrombosis (JCS, 3/3). The median fall in portal pressure was more in SAS (12.1 mm Hg), and operative time more in JCS, 8.4 hours (range, 5-9 hours). During a median follow-up of 36 months (6-54 months), shunt thrombosis had been reported in all cases of LGERS, and less in SAS (3/12). Variceal regression rate was high in SAS, and least in LGERS. Hypersplenism had reversed in all patients, and 6/31 patients had a recurrent bleed. Unconventional shunt surgery is effective in patients unsuited for other shunts, especially PSRS, and it achieves the desired effects in a significant proportion of patients.

Baveno VI and VII criteria are not suitable for screening for large varices or clinically significant portal hypertension in patients with hepatocellular carcinoma.

Baveno VI and VII criteria are used in patients with cirrhosis to rule out large size oesophageal varices (EV) and rule in/out clinically significant portal hypertension (CSPH). To evaluate their diagnostic performance in these patients. We retrospectively included all patients with Child-Pugh A cirrhosis and HCC who had endoscopy, liver stiffness measurement (LSM) and platelet count within 6 months. They were classified according to the BCLC stage. Favourable Baveno VI criteria were defined by LSM < 20 kPa and platelets > 150 G/L (to rule out large EV), favourable Baveno VII criteria if LSM ≤ 15 kPa and platelets ≥ 150 G/L (to rule out CSPH, which was defined by a HVPG ≥ 10 mm Hg. We included 185 patients; 46% wereBCLC-0/A, 28% BCLC-B and 26% BCLC-C. EV were present in 44% (23% large), and HVPG ≥ 10 mm Hg in 42% (mean 8 mm Hg). In patients with favourable Baveno VI criteria, 8% of the whole cohort (Se 93%, NPV 92%), 11% of BCLC-0-A (Se 89%, NPV 89%) and 10.0% of BCLC-C patients (Se 91%, NPV 90%) had large EV. Among patients with HVPG < 10 mm Hg, 6% had large EV and 17% small. CSPH was present in 23% of patients with favourable Baveno VII criteria among the whole cohort, and in 25% of those with BCLC-0/A. The specificity of LSM ≥ 25 kPa to rule in CSPH was 48%. Favourable Baveno VI criteria are not appropriate to rule out the presence of high-risk EV, or Baveno VII criteria to rule CSPHin/out in patients with HCC.

Quantitative computed tomography‐based approaches for noninvasive diagnosis of portal hypertension in patients with cirrhosis

AbstractNoninvasive diagnosis of portal hypertension in patients with cirrhosis can be achieved using different methods, including laboratory tests and imaging. The Baveno VII consensus suggested that liver stiffness measurements and platelet counts were sufficient for assessing the presence of clinically significant portal hypertension. However, computed tomography (CT) is frequently performed in patients with cirrhosis, and numerous studies have established the possibility of an opportunistic noninvasive diagnosis of portal hypertension using CT. These studies have utilized radiomics, volumetric changes in the liver and spleen, quantitative assessment of liver surface nodularity, and more advanced techniques based on computational fluid dynamics. This review summarizes the main original studies related to the quantitative CT‐based noninvasive diagnosis of portal hypertension.

SAT-327 - Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with advanced chronic liver disease: an individual patient meta-analysis

SAT-327 - Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with advanced chronic liver disease: an individual patient meta-analysis

THU-261 - Albumin levels are associated with portal hypertension in patients with porto sinusoidal vascular disorder

THU-261 - Albumin levels are associated with portal hypertension in patients with porto sinusoidal vascular disorder

FRI-274 - Baveno VI and VII criteria are not suitable for screening of large size esophageal varices and clinically significant portal hypertension in patients with HCC

FRI-274 - Baveno VI and VII criteria are not suitable for screening of large size esophageal varices and clinically significant portal hypertension in patients with HCC

More precise measurement of irregular splenic volume in cirrhotic patients with portal hypertension

Splenomegaly often occurs in cirrhotic patients with portal hypertension (PHT), and therefore, the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question in these patients. Here, we developed a novel approach to assess true splenic volume more precisely. High-quality thin-slice computed tomography data of 112 cirrhotic patients with PHT were obtained and reviewed. Both the conventional measurement and a novel formula obtained from 3-dimensional reconstruction software were used to estimate splenic volume, and the accuracy was compared and verified. In PHT patients, the splenic volume calculated using the conventional method was significantly less than that calculated using the 3-dimensional software. We found that the splenic volume was significantly positively correlated with splenic indices of length (L), thickness (T), and width (W) and also the diameter of the splenic vein. Using these indices, we propose 2 novel formulas using the software to estimate the splenic volume more accurately: SV = 69.686 × L + 53.077 × W + 103.525 × T + 314.510 × diameter of splenic vein −2266.209 (p < 0.01, R2 = 0.805). And a more practical simplified formula: SV' = 0.504 × L × W × Τ + 319.762 × diameter of splenic vein −81.66 (p < 0.01, R2 = 0.784). Although the conventional formula has been widely used for years, it is not suitable for an enlarged spleen. We developed 2 novel formulas for estimating splenic volume from clinical data that were more appropriate for cirrhotic patients with PHT.

Comparison of long-term outcomes of splenectomy with periesophagogastric devascularization and transjugular intrahepatic portosystemic shunt in treating cirrhotic portal hypertension patients with recurrent variceal bleeding

PurposeTransjugular intrahepatic portosystemic shunt (TIPS) and splenectomy with periesophagogastric devascularization (SPD) are widely used to treat cirrhotic portal hypertension (PH) and prevent variceal rebleeding. However, direct comparisons between these two approaches are rare. This study was designed to compare the long-term outcomes of TIPS and SPD in patients with cirrhotic PH and variceal rebleeding.MethodsThe study included cirrhotic PH patients with a history of gastroesophageal variceal bleeding between 18 and 80 years of age who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to January 2022. Patients were enrolled into two groups according to TIPS or SPD was performed. Baseline characteristics were matched using propensity score matching (PSM).ResultsA total of 230 patients underwent TIPS, while 184 underwent SPD. PSM was carried out to balance available covariates, resulting in a total of 83 patients in the TIPS group and 83 patients in the SPD group. Patients in SPD group had better liver function during 60 months follow-up. Five-year overall survival rates in SPD group and TIPS group were 72 and 27%, respectively, at 2 years were 88 and 86%, respectively. The 2- and 5-year freedom from variceal rebleeding rates were 95 and 80% in SPD group and 80 and 54% in TIPS group.ConclusionsSPD is clearly superior to TIPS in terms of OS and freedom from variceal rebleeding in patients with cirrhotic PH. In addition, SPD improved liver function in patients with cirrhotic PH.

Soluble Guanylyl Cyclase Activator BI 685509 Reduces Portal Hypertension and Portosystemic Shunting in a Rat Thioacetamide-Induced Cirrhosis Model.

Portal hypertension (PT) commonly occurs in cirrhosis. Nitric oxide (NO) imbalance contributes to PT via reduced soluble guanylyl cyclase (sGC) activation and cGMP production, resulting in vasoconstriction, endothelial cell dysfunction, and fibrosis. We assessed the effects of BI 685509, an NO-independent sGC activator, on fibrosis and extrahepatic complications in a thioacetamide (TAA)-induced cirrhosis and PT model. Male Sprague-Dawley rats received TAA twice-weekly for 15 weeks (300-150 mg/kg i.p.). BI 685509 was administered daily for the last 12 weeks (0.3, 1, and 3 mg/kg p.o.; n = 8-11 per group) or the final week only (Acute, 3 mg/kg p.o.; n = 6). Rats were anesthetized to measure portal venous pressure. Pharmacokinetics and hepatic cGMP (target engagement) were measured by mass spectrometry. Hepatic Sirius Red morphometry (SRM) and alpha-smooth muscle actin (αSMA) were measured by immunohistochemistry; portosystemic shunting was measured using colored microspheres. BI 685509 dose-dependently increased hepatic cGMP at 1 and 3 mg/kg (3.92 ± 0.34 and 5.14 ± 0.44 versus 2.50 ± 0.19 nM in TAA alone; P < 0.05). TAA increased hepatic SRM, αSMA, PT, and portosystemic shunting. Compared with TAA, 3 mg/kg BI 685509 reduced SRM by 38%, αSMA area by 55%, portal venous pressure by 26%, and portosystemic shunting by 10% (P < 0.05). Acute BI 685509 reduced SRM and PT by 45% and 21%, respectively (P < 0.05). BI 685509 improved hepatic and extrahepatic cirrhosis pathophysiology in TAA-induced cirrhosis. These data support the clinical investigation of BI 685509 for PT in patients with cirrhosis. SIGNIFICANCE STATEMENT: BI 685509 is an NO-independent sGC activator that was tested in a preclinical rat model of TAA-induced nodular, liver fibrosis, portal hypertension, and portal systemic shunting. BI 685509 reduced liver fibrosis, portal hypertension, and portal-systemic shunting in a dose-dependent manner, supporting its clinical assessment to treat portal hypertension in patients with cirrhosis.

Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial

Up-to-datedata about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients. We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL. Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups (P<0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan (P<0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively (P<0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding. Short course of vonoprazan 20mg/day is safe and superior to pantoprazole 40mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.

Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders.

Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression. A retrospective review was performed on a cohort of 58 patients (39 males) with DC/TBD who were prospectively evaluated at a single institute from 2002 to 2019. The median age at initial assessment was 18 (1.4-67.6) years, and median follow-up duration was 6 (1.4-8.2) years. Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non- TINF2 DC/TBD patients. Liver abnormality (defined at baseline assessment by laboratory and/or radiological findings) was present in 72.4% of patients with predominantly cholestatic pattern of liver enzyme elevation. Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the 6-year follow-up; this progression was mainly seen in patients with recessive or TINF2 -associated DC. Significant risk factors associated with progression included the presence of pulmonary or vascular disease. Our experience shows a high prevalence of cholestatic pattern of liver abnormality with progression to portal hypertension in patients with DC/TBD. Presence of pulmonary and/or vascular disease in patients with recessive or TINF2 DC was an important predictor of liver disease progression, suggesting the need for increased vigilance and monitoring for complications in these patients.

The Role of Shear-Wave Elastography of the Spleen in Ruling out the Presence of High-Risk Varices in Non-Alcoholic Fatty Liver Disease (NAFLD)

The progression of liver fibrosis and the presence of portal hypertension are two key points in the follow-up and severity assessment of patients with chronic liver disease. Objective evaluation of such aspects has proven to be difficult due to the lack of reproducible and standardized non-invasive methods. Therefore, the aim of this study was to evaluate whether spleen stiffness (SS) can rule out the presence of high-risk varices (HRVs) in patients with non-alcoholic fatty liver disease (NAFLD). We designed a prospective follow-up of a cohort of 48 consecutive patients diagnosed with compensated advanced chronic liver disease (cACLD) due to NAFLD, between January 2020 and January 2021. After clinical evaluation, laboratory testing, ultrasonography (US), and shear-wave elastography (2D-SWE.GE) of both the liver and the spleen, patients were endoscopically screened for esophageal varices, gastric varices, and portal hypertensive gastropathy. Correlations and predictors were assessed. After univariate, multivariate, and predictive analyses, SS could be referred to as an independent predictor for high-risk varices (AUROC 0.987, p &lt; 0.001, OR 4.985, 95% CI: 1.57–15.73, p = 0.006), with a calculated cutoff value of 17.95 kPa. These results are consistent with those of other, similar studies using both 2D-SWE.GE and a similar module (2D-SWE.SSI) in patients with metabolic liver disease. When confirmed by subsequent larger studies, SS could potentially become a useful non-invasive tool in the assessment of clinically significant portal hypertension in patients with advanced fatty liver disease.

Splenic Artery Embolism in Liver Transplant Patients: A Single-Center Experience.

Hypersplenism, portal hypertension, and ascites have been seen after liver transplants. Patients are usually treated medically with refractory patients potentially undergoing splenectomy. Splenic artery embolism (SAE) is an alternative that can be performed to limit the surgical intervention that may have the benefit of improving portal hypertension. Few studies have studied the effect on main portal vein (MPV) velocities and hepatic artery resistive indices (HARIs) which may be beneficial as markers of portal hypertension. This study aims to evaluate the efficacy and safety of interventional radiology (IR)-guided SAE for the management of portal hypertension in patients who have had liver transplants. A retrospective analysis was conducted on liver transplant patients who had undergone IR-guided SAE post-transplant at a single tertiary transplant center from 2012 to 2022. The primary outcome of intervention efficacy was quantified by peak HARIs and MPV velocities. Ultrasound with Doppler obtained before and after the intervention was reviewed for these parameters. Secondary outcomes included adverseeventsat the time of the procedure and within one year of the procedure, the need for splenectomy, and spleen size. Twenty-eight patients met the criteria for inclusion. The mean age of patients was 52.5 years (21-71 years) and the time after transplant was 149.5 days (2-1588 days). About 96.4% of SAEs were technically successful (n=27). Twenty-one patients had MPV velocities available, and 24 had peak HARIs available. In these patients, HARIs decreased by an average of 0.063 (95% CI 0.014-0.112) after SAE. MPV velocity decreased by an average of 47.2 cm/s (95% CI 27.3-67.1) after SAE. About 10.4% of patients (n=3) developed a procedure-related complication, all of which were femoral access site aneurysms. No (0) patients suffered from bleeding, infections, or abscesses after the procedure. About 10.7% of patients (n=3) required splenectomy after SAE: one splenectomy was due to technical failure and two were due to refractory symptoms. We performed one of the first analyses on MPV and RI and showed that our patients saw an improvement post-embolization with a theoretical improvement in portal hypertension. The complication rate and risk of infection seem to be acceptable risks, making SAE a feasible option for management.

To TIPS or Not to TIPS in High Risk of Variceal Rebleeding and Acute-on-Chronic Liver Failure.

Variceal bleeding is a consequence of severe portal hypertension in patients with liver cirrhosis. Although the rate of bleeding has decreased over time, variceal bleeding in the presence of acute-on-chronic liver failure (ACLF) carries a high risk of treatment failure and short-term mortality. Treatment and/or removal of precipitating events (mainly bacterial infection and alcoholic hepatitis) and decrease of portal pressure may improve outcome of patients with acute decompensation or ACLF. Transjugular intrahepatic portosystemic shunts (TIPSs), especially in the preemptive situation, have been found to efficiently control bleeding, prevent rebleeding, and reduce short-term mortality. Therefore, TIPS placement should be considered as an option in the management of ACLF patients with variceal bleeding.

Portal hypertension in patients with hepatocellular carcinoma and immunotherapy: prognostic relevance of CT-morphologic estimates

BackgroundClinically significant portal hypertension (CSPH) has been identified as an important prognostic factor in patients with hepatocellular carcinoma (HCC) undergoing curative treatment. This study aimed to assess PH estimates as prognostic factors in patients with HCC treated with immunotherapy.MethodsAll patients with HCC treated with an immunotherapeutic agent in first or subsequent lines at our tertiary care center between 2016 and 2021 were included (n = 50). CSPH was diagnosed using the established PH score for non-invasive PH estimation in pre-treatment CT data (cut-off ≥ 4). Influence of PH on overall survival (OS) and progression-free survival (PFS) was assessed in uni- and multivariable analyses.ResultsBased on the PH score, 26 patients (52.0%) were considered to have CSPH. After treatment initiation, patients with CSPH had a significantly impaired median OS (4.1 vs 33.3 months, p < 0.001) and a significantly impaired median PFS (2.7 vs 5.3 months, p = 0.02). In multivariable Cox regression, CSPH remained significantly associated with survival (HR 2.9, p = 0.015) when adjusted for established risk factors.ConclusionsNon-invasive assessment of CSPH using routine CT data yielded an independent prognostic factor in patients with HCC and immunotherapy. Therefore, it might function as an additional imaging biomarker to detect high-risk patients with poor survival and possibly for treatment decision making.

The rationale and study design of two phase II trials examining the effects of BI 685509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis

BackgroundClinically significant portal hypertension (CSPH) drives cirrhosis-related complications (i.e. hepatic decompensation). Impaired nitric oxide (NO) bioavailability promotes sinusoidal vasoconstriction, which is the initial pathomechanism of CSPH development. Activation of soluble guanylyl cyclase (sGC), a key downstream effector of NO, facilitates sinusoidal vasodilation, which in turn may improve CSPH. Two phase II studies are being conducted to assess the efficacy of the NO-independent sGC activator BI 685509 in patients with CSPH due to various cirrhosis aetiologies.MethodsThe 1366.0021 trial (NCT05161481) is a randomised, placebo-controlled, exploratory study that will assess BI 685509 (moderate or high dose) for 24 weeks in patients with CSPH due to alcohol-related liver disease. The 1366.0029 trial (NCT05282121) is a randomised, open-label, parallel-group, exploratory study that will assess BI 685509 (high dose) alone in patients with hepatitis B or C virus infection or non-alcoholic steatohepatitis (NASH) and in combination with 10 mg empagliflozin in patients with NASH and type 2 diabetes mellitus for 8 weeks. The 1366.0021 trial will enrol 105 patients, and the 1366.0029 trial will enrol 80 patients. In both studies, the primary endpoint is the change from baseline in hepatic venous pressure gradient (HVPG) until the end of treatment (24 or 8 weeks, respectively). Secondary endpoints include the proportion of patients with an HVPG reduction of >10% from baseline, the development of decompensation events and the change from baseline in HVPG after 8 weeks in the 1366.0021 trial. In addition, the trials will assess changes in liver and spleen stiffness by transient elastography, changes in hepatic and renal function and the tolerability of BI 685509.DiscussionThese trials will enable assessment of the short-term (8 weeks) and longer-term (24 weeks) safety of BI 685509, and the effect of sGC activation by BI 685509 on CSPH due to various cirrhosis aetiologies. The trials will use central readings of the diagnostic gold standard HVPG for the primary endpoint, and changes in established non-invasive biomarkers, such as liver and spleen stiffness. Ultimately, these trials will provide key information for developing future phase III trials.Trial registration1366.0021: EudraCT no. 2021–001285-38; ClinicalTrials.gov NCT05161481. Registered on 17 December 2021, https://www.clinicaltrials.gov/ct2/show/NCT05161481.1366.0029: EudraCT no. 2021–005171-40; ClinicalTrials.gov NCT05282121. Registered on 16 March 2022, https://www.clinicaltrials.gov/ct2/show/NCT05282121.

Prediction of Esophageal Varices by Non-Invasive Markers in Patients of Hepatic Cirrhosis due To Chronic Hepatitis C

Background: Esophageal varices develop as a consequence of portal hypertension in patients with chronic liver disease. Predicting the varices by non-invasive methods at the time of registration is likely to predict the need for prophylactic β blockers or endoscopic variceal ligation in patients with cirrhosis and portal hypertension. Objective: To evaluate the accuracy of combined non-invasive parameters in predicting the presence of esophageal varices in patients with hepatic cirrhosis due to chronic hepatitis C, using the positive predictive value (PPV) as a measure of performance. Methods: In this cross-sectional study conducted in the Department of Medicine, Unit-I, Sir Ganga Ram Hospital, Lahore, 125 patients fulfilling the inclusion criteria were included. Platelet count, Prothrombin Time/International Normalized Ratio (PT/INR) and portal vein diameter was assessed. Upper gastrointestinal endoscopy was done in all patients to check the presence or absence of esophageal varices. Results: Mean age of the patients was 52.52±8.39 years with 64% males. Mean PT was 10.09±3.13, mean INR was 1.75±0.22, mean platelet count was 83.56±13.47 while mean portal vein diameter was 13.79±0.84. In 61 patients (48.8%) esophageal varices were present on endoscopy and in 85 patients (68%) esophageal varices were predicted by combined non-invasive parameters. Positive predictive value of combined non-invasive parameters was 71.7%. Practical implications: Noninvasive predictors can be used as a screening tool to decide need for preventive drug therapy in esophageal varices and thus help reduce the workload and financial burden of routine endoscopies in all cirrhosis patients. Conclusion: The results suggest that combined non-invasive parameters may be a useful tool in the prediction of esophageal varices in patients with hepatic cirrhosis Keywords: Esophageal varices, Non-invasive predictors, Portal hypertension