Mean Hepatic Venous Pressure Gradient Research Articles

Exploring the Role of Hepatic Venous Pressure Gradient Values in Patients with Acute on Chronic Liver Failure: A Pilot Study

Abstract Introduction: Acute on chronic liver failure (ACLF) has been a difficult entity to define. The use of the hepatic venous pressure gradient (HVPG) for the measurement of portal pressure is well established in chronic liver disease. This is based on data showing that improvements in the HVPG are associated with improvements in clinical outcomes. Methods: The study was a prospective observational study conducted in the department of gastroenterology of a tertiary care center in Northern India for 2 years. Thirty cases each of ACLF (Group I), compensated cirrhosis (Group II), and decompensated cirrhosis (Group III) were enrolled. We evaluated the role of HVPG values and complications in patients with liver disease. Results: The mean age of the cohort was 44.2 ± 7.3 years. The most common etiology of ACLF noted in the study was alcohol (54.4%), followed by infections by hepatotropic viruses (22.2%). ACLF has high short-term mortality compared to compensated and decompensated cirrhotics. Compensated cirrhosis is associated with the lower risk of bleed. The model for end-stage liver disease score was higher among the patients of ACLF (25.2 ± 3.1) and decompensated cirrhosis (23.93 ± 2.8) than compensated cirrhotics (9.7 ± 1.8). The mean HVPG was 12.3 ± 7.5 mmHg, which was significantly higher than the normal gradient. It was also noted that the HVPG was significantly higher in the ACLF and decompensated cirrhotics. Conclusions: HVPG monitoring is recommended in ACLF and decompensated liver disease at admission to stratify the risk of early mortality.

The impact of transmembrane 6 superfamily 2 (TM6SF2) rs58542926 on liver-related events in patients with advanced chronic liver disease.

Genetic factors such as the transmembrane 6 superfamily 2 (TM6SF2) rs58542926 single nucleotide variant(SNV) modulate the susceptibility for (advanced) chronic liver disease ([A]CLD). However, the impact of this variant in patients who have already progressed to ACLD is unknown. The association between TM6SF2-rs58542926 genotype and liver-related events was evaluated in 938 ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement. Mean HVPG was 15±7 mmHg and mean UNOS MELD (2016) 11±5 points. Viral hepatitis (n=495, 53%) was the most common cause of ACLD, followed by alcohol-related (ARLD; n=342, 37%) and non-alcoholic fatty liver disease (NAFLD; n=101, 11%). While 754 (80%) patients harboured the TM6SF2 wild-type (C/C), 174 (19%) and 10 (1%) patients had one or two T-alleles. At baseline, patients with at least one TM6SF2 T-allele had more pronounced portal hypertension (HVPG: 16±7 vs. 15±7 mmHg; p=0.031), higher gamma-glutamyl transferase levels (123 [63-229] vs. 97 [55-174] UxL-1; p=0.002), and more commonly hepatocellular carcinoma (17% vs. 12%; p=0.049). Harbouring the TM6SF2 T-allele was associated with the composite endpoint hepatic decompensation/liver transplantation/liver-related death (SHR: 1.44 [95%CI: 1.14-1.83]; p=0.003). This was confirmed in multivariable competing risk regression analyses that were adjusted for severity of portal hypertension and hepatic dysfunction at baseline. The TM6SF2 variant modulates liver disease progression beyond the development of ACLD, as it modifies the risks of hepatic decompensation and liver-related death, independently of baseline liver disease severity.

Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension

BackgroundThe hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension.MethodsA total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson’s correlation coefficient were used for analysis.ResultsConventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively.ConclusionsInnovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.

Characterization of a prothrombotic phenotype using thrombin generation and thrombin activity in cirrhosis and portal hypertension

BackgroundPatients with advanced chronic liver disease (ACLD) may develop a prothrombotic phenotype that seems to be more pronounced with more severe liver dysfunction. An imbalance of endogenous pro- and anticoagulants is not fully captured by routine coagulation assays. MethodsIn a cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement, we assessed thrombin generation (TGA) using two commercially available assays (Technothrombin and Thrombinoscope) with and without addition of soluble thrombomodulin (TM), as well as thrombin activity, alongside a panel of coagulation parameters. ResultsThe cohort encompassed 37 patients (median age 55.3 years, mean HVPG 16 ± 5 mm Hg). In the TM-modified Thrombinoscope TGA, the endogenous thrombin generation potential (ETP) was significantly increased in Child-Pugh-Score (CPS) B/C patients (N = 23, 62 %) compared to CPS A patients (N = 14, 38 %) (ETP: 546 nM∗min (443–696) vs. 404 nM∗min (289–573), p = 0.028). Using the Technothrombin TGA without TM, patients with CPS B/C had decreased ETP compared to CPS A patients (ETP: 2792 ± 1336 nM∗min vs. 5040 ± 816 nM∗min, p < 0.001) and with addition of TM (final concentration: 5 nM; ETP: 2545 ± 1327 nM∗min vs. 4824 ± 929 nM∗min, p < 0.001). Thrombin activity levels were 0.6pM in median (0.2–1.6pM) and above the level of detectability (0.10pM) in 94.6 % of patients but were not correlated to severity of cirrhosis (CPS A 0.7pM vs CPS B/C 0.4pM, p = 0.377) nor to parameters of TGA. ConclusionThrombin plasma levels are elevated in liver disease patients without apparent correlation to TGA or severity of cirrhosis. TGAs can be modified with TM to enable protein C-dependent anticoagulation, but result in differences with regard to severity of liver disease.

Management of Ascites Following Deceased Donor Liver Transplantation: A Case Series.

Background.Persistent ascites after orthotropic liver transplantation has numerous causes and can be challenging to manage. This study aimed to determine the outcomes associated with conservative and endovascular intervention of posttransplant ascites after deceased donor liver transplantation.Methods.Adult (≥18 y) liver transplant recipients (between 2006 and 2019) who underwent hepatic venous pressure studies to investigate posttransplant ascites were included in this retrospective study. Comparisons were made between those who were managed with conservative therapy versus endovascular intervention and were also based on hepatic venous wedge pressure gradient (normal [≤10 mm Hg] versus elevated [>10 mm Hg]).Results.A total of 30 patients underwent hepatic venography to investigate ascites during the study period. The median time from transplant to venography was 70 d. At least 1 endovascular intervention was performed in 18 of 30 patients (62%), and 12 of 30 patients (38%) were managed conservatively. Endovascular interventions included angioplasty (n = 4), hepatic vein stenting (n = 9), or a transjugular intrahepatic portosystemic shunt (n = 7). The mean (range) hepatic venous wedge pressure gradient for the conservative and endovascular intervention groups was 12 mm Hg (3–23) and14 mm Hg (2–35), respectively. At a 6-mo follow-up, ascites resolved in 6 of 12 patients (50%) and 11 of 18 patients (61%) in the medical management and endovascular groups, respectively. The graft survival rates at 6 and 12 mo were (7/12 [58%] versus 17/18 [94%], P = 0.02) and (7/12 [58%] versus 14/18 [78%], P = 0.25), respectively.Conclusions.Despite medical or endovascular intervention, resolution of ascites is achieved in <60% of patients with persistent ascites. Biopsy findings and venographic pressure studies should be carefully integrated into the management of posttransplant ascites.

Evaluating short-term outcomes of the value of sound touch elastography (STE) following the treatment for Budd–Chiari syndrome (BCS): a case series study

To investigate the value of sound touch elastography (STE) in the evaluation of short-term therapeutic effect of Budd-Chiari syndrome (BCS) by measuring liver stiffness (LS), and in addition, to analyse the relationships between liver function, pressure gradient of the hepatic veins, and LS. A case series study was conducted at Affiliated Hospital of Xuzhou Medical University from August 2020 to December 2020. Patients diagnosed with BCS were recruited prospectively and grouped according to Child-Pugh grade before endovascular therapy. LS was measured using STE before and after therapy. Comparisons between the LS and hepatic venous pressure gradient (HVPG) changes of patients were tested with paired sample t-tests. A total of 46 patients (23 males and 23 females) were included in this study. According to the Child-Pugh scoring criteria, 24 patients were classified as grade A, 16 as grade B, and 6 as grade C. LS was significantly different between the three groups (F=127.01, p<0.001). Post-treatment LS was significantly lower than pre-treatment (p<0.001). The mean HVPG before treatment was 13.02±3.82 mmHg and decreased after intervention (p<0.001). The STE is a potential tool for evaluating short-term therapeutic effect of BCS patients.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUNDThe liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis.AIMTo analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT.METHODSFrom January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed.RESULTSThe mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively.CONCLUSIONMeasurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Impact of propofol sedation on the diagnostic accuracy of hepatic venous pressure gradient measurements in patients with cirrhosis

BackgroundMeasurement of the hepatic venous pressure gradient (HVPG) is the gold standard to evaluate the presence and severity of portal hypertension. The procedure is generally safe and well tolerated, but nevertheless, some patients demand for sedation. However, it is unknown whether propofol sedation would impair the accuracy of portal pressure measurements.MethodsThis is a prospective observational cohort study including cirrhotic patients with suspected portal hypertension undergoing invasive measurement of HVPG. Measurements of HVPG were performed in awake condition as well as under sedation with propofol infusion.ResultsIn total, 37 patients were included. Mean HVPG in awake condition was 15.9 mmHg (IQR 13–19) and during sedation 14.1 mmHg (IQR 12–17). While measures of free hepatic vein pressure (FHVP) were not altered after propofol sedation (p = 0.34), wedged hepatic vein pressure values (WHVP) decreased in an average by 2.05 mmHg (95% CI − 2.46 to − 1.16; p < 0.001) which was proportional to the magnitude of HVPG. In 31 out of 37 patients (83.8%), portal hypertension with HVPG ≥ 12 mmHg was found. Under sedation with propofol, two patients (5.4%) with borderline values would have been incorrectly classified as < 12 mmHg. After adjustment for the average difference of − 10%, all patients were correctly classified. Intraclass correlation coefficient between HVPG measurement in awake condition and under propofol sedation was 0.927 (95% CI 0.594–0.975).ConclusionsPropofol sedation during HVPG measurements is generally safe, however it may lead to relevant alterations of HVPG readings.

Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis.

Alcoholic hepatitis (AH) lacks specific histological staging. A novel fibrosis staging that encompasses perisinusoidal fibrosis and cirrhosis sub-stages, substantiated by Hepatic venous pressure gradient (HVPG) and automated fibrosis quantification, is imperative. To correlate novel histological staging system of AH with second-harmonic generation microscopy (SHG)-based q-fibrosis, HVPG, and activated hepatic stellate cells (HSCs). Liver biopsies of AH (n = 175) were staged semi-quantitatively as F0, F1, F2, F3A and F3B and Laennec substages of cirrhosis 4A, 4B and 4C. Stages were correlated with SHG q-fibrosis parameters, HVPG and HSCs. Mean age 41.2 ± 9.4 years, 96.6% males, bilirubin 20.58 ± 8.0 mg/dl and Maddrey's discriminant function 78.9 ± 36.7 displayed advanced fibrosis in 98.6%. With increasing histological stages, an increase in q-fibrosis indices and mean HVPG (p < 0.0001) were recorded; stage 4C showed the most significant difference from other stages (p < 0.000). Stages 3A and 3B were comparable with the stages 4A and 4B, respectively, for q-fibrosis (p = 1) and HVPG (p = 1). HSCs (> 30%) were significantly higher in stage 3 (75%) compared with 4 (49%) and 2 (59%), p = 0.018. Overall agreement for histological staging was excellent for all stages (0.82). SHG quantified fibrosis and HVPG corroborates the novel histological staging of AH. Expansive PCF matches with collagen content and clinical severity to early sub-stages of cirrhosis. This highlights the need for an accurate quantification and inclusion of PCF as a separate stage. SHG-based quantification can be a useful adjunct to histological fibrosis staging systems.

Noninvasive diagnosis of portal hypertension using gadoxetate DCE-MRI of the liver and spleen.

To assess the performance of gadoxetate dynamic contrast-enhanced (DCE) MRI of the liver and spleen for noninvasive diagnosis of portal hypertension (PH). Thirty-five patients (M/F 22/13, mean age 55 years) with chronic liver disease who underwent hepatic venous pressure gradient (HVPG) measurements were prospectively enrolled in this IRB-approved study. All patients underwent multiparametric MRI including gadoxetate DCE-MRI acquisition. Model-based and model-free DCE-MRI analyses were performed. The correlation between DCE-MRI parameters and HVPG was assessed. ROC analysis was employed to determine the diagnostic performance of DCE-MRI parameters alone and in combination for prediction of PH and clinically significant (CS)PH (HVPG > 5 and ≥ 10 mmHg, respectively). Mean HVPG was 7.0 ± 5.0 mmHg (range 0-18 mmHg). Twenty-one (60%) patients had PH, of whom 9 had CSPH. Modeled liver uptake fraction fi and uptake rate ki and model-free parameters liver upslope and uptake were all significantly negatively correlated with HVPG (r range - 0.490 to - 0.398, p value range 0.003-0.018), while spleen interstitial fraction ve was significantly positively correlated with HVPG (r = 0.336, p = 0.048). For PH diagnosis, liver ki showed the best diagnostic performance with an AUC, sensitivity, and specificity of 0.74 (confidence interval (CI) 0.57-0.91), 71.4%, and 78.6%. The combination of liver ki and spleen ve was selected as the best classifier for diagnosis of CSPH with an AUC, sensitivity, and specificity of 0.87 (CI 0.75-0.99), 100%, and 73.1%. Our results demonstrate the potential utility of hepatocyte uptake parameters and spleen interstitial fraction obtained with gadoxetate DCE-MRI for the diagnosis of PH and CSPH. • Liver uptake and spleen interstitial fraction estimates from gadoxetate DCE-MRI are significantly correlated with portal pressure measurements. • Liver uptake rate shows good diagnostic performance for the diagnosis of portal hypertension. • The combination of liver uptake rate with spleen interstitial fraction exhibits excellent diagnostic performance for the diagnosis of clinically significant portal hypertension.

Invasive measurement of portal hypertension in the hemodynamics laboratory as an important element of qualification for the treatment of esophageal varices: A single-center experience

Introduction: The measurement of hepatic venous pressure gradient (HVPG) is an essential prognostic factor in subjects with chronic liver disorders. Aim: The present study aimed to present the feasibility and applicability of HVPG in the modern hemodynamics laboratory in patients with liver cirrhosis as a stage for qualification in variceal band ligation (VBL). Material and methods: We included 78 patients with liver cirrhosis and esophageal varices, who had HVPG measurements taken at the hemodynamics laboratory between January 2015 and January 2019. Results and discussion: The mean age was 55.5 ± 10.9 years, and 66.7% were males. The most common cause of liver cirrhosis was alcohol abuse (65.4%), and the most common varices stage was 3 (83.3%). The mean HVPG was 16.3 ± 6.2 mm Hg. In total, 67 (85.9%) patients had HVPG over 10 mm Hg and underwent VBL. No periprocedural complications were observed. At 12 months, recurrent hospitalizations were observed in 67 (85.9%), 5 (6.4%)had cirrhosis-related bleeding episodes, and 4 (5.1%) patients died. Conclusions: HVPG measurement is a feasible, safe and reproducible procedure that provides valuable diagnostic/prognostic information and helps make therapeutic decisions. This procedure can be done quickly in the modern hemodynamics laboratory.

Impact of Intrahepatic Venovenous Shunt on Hepatic Venous Pressure Gradient Measurement

PurposeTo quantitatively analyze the impact of intrahepatic venovenous shunt (IHVS) on hepatic venous pressure gradient (HVPG) measurement. Materials and MethodsFrom 2015 to 2019, 222 HVPG measurements performed during transjugular intrahepatic portosystemic shunt creation were eligible for this study. Digital subtraction angiography (DSA) software color-coded each pixel of a two-dimensional DSA series by time-intensity curve to classify IHVS. Different degrees of IHVS were found in 36.5% of patients (81/222). Mild IHVS was found in 10.8% of patients (24/222), moderate IHVS was found in 10.8% of patients (24/222), and severe IVHS was found in 14.9% of patients (33/222). ResultsMean wedged hepatic vein pressure (WHVP) and HVPG were significantly lower in patients with IHVS compared with patients without IHVS (WHVP: 17.78 mm Hg ± 7.00 vs 24.89 mm Hg ± 8.69, P = .001; HVPG: 11.93 mm Hg ± 5.76 vs 18.6 mm Hg ± 6.85, P < .001). Mild IHVS had little effect on WHVP and HVPG. Mean WHVP and HVPG were 11 mm Hg lower in patients with moderate IHVS (WHVP: 20.38 mm Hg ± 8.38 vs 31.5 mm Hg ± 9.39, P = .026; HVPG: 13.88 mm Hg ± 6.33 vs 25.00 mm Hg ± 9.81, P < .001) and 15 mm Hg lower in patients with severe IHVS (WHVP: 13.45 mm Hg ± 5.28 vs 28.64 mm Hg ± 6.38, P = .017; HVPG: 8.27 mm Hg ± 3.85 vs 23.45 mm Hg ± 6.95, P < .001) than mean portal vein pressure and portal vein gradient. ConclusionsFor patients with moderate or severe IHVS, HVPG might greatly underestimate the actual value of portal vein pressure, and the portal vein should be catheterized to measure portal pressure.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. Between January 2012 and December 2019 (96months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8mmHg (range: 0-15mmHg). The mean hepatic venous pressure gradient was 3.6±2.6mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 5.9±4.2mmHg (range: 1-15mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47mmHg (range: 0-15mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 10.3±4.1mmHg (range: 5-15mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75days (range: 0-8days). The mean wedge portosystemic gradient was 4.5±3.1mmHg (range: 2-9mmHg) and the mean portosystemic gradient was 14.5±3.7mmHg (range: 12-20mmHg) (P=0.006). HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease.

Background and aimsNon‐O blood type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non‐O‐BT is a risk factor for PVT and (II) whether non‐O‐BT impacts VWF/factor VIII in patients with ACLD.MethodsRetrospective analysis comprising two cohorts: (I) “US” including all adult liver transplantations in the US in the MELD era and (II) “Vienna” comprising patients with a hepatic venous pressure gradient (HVPG) ≥6 mmHg.Results(I) The “US cohort” included 84 947 patients (non‐O: 55.43%). The prevalence of PVT at the time of listing (4.37% vs 4.56%; P = .1762) and at liver transplantation (9.56% vs 9.33%; P = .2546) was similar in patients with O‐ and non‐O‐BT. (II) 411 patients were included in the “Vienna cohort” (non‐O: 64%). Mean HVPG was 18(9) mmHg and 90% had an HVPG ≥10 mmHg. Patients with non‐O‐BT had slightly increased VWF levels (318(164)% vs 309(176)%; P = .048; increase of 23.8%‐23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non‐O‐BT explained only 1% of the variation in VWF and had no effect on FVIII.ConclusionsAlthough non‐O‐BT impacts VWF in patients with early stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non‐O‐BT had no impact on FVIII. These findings may explain the absence of an association between non‐O‐BT and PVT in patients with advanced cirrhosis.

Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial.

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

Lower Gastrointestinal Bleeding in Patients With Cirrhosis—Etiology and Outcomes

Lower gastrointestinal bleeding (LGIB) is a common clinical problem, and may be more prevalent among patients with cirrhosis, especially in the setting of portal hypertension and coagulopathy. However, there is extremely little data available on the subject of LGIB in patients with cirrhosis. Therefore, the primary objective of this study was to better understand the etiology and outcomes of cirrhotic patients hospitalized with LGIB. We analyzed 3,735 cirrhotic patients admitted to the Medical University of South Carolina between January 2011 and September 2018, and identified patients admitted with a primary diagnosis of hematochezia or bright red blood per rectum. Thirty patients with cirrhosis and LGIB were included in the cohort. The mean age was 56 ± 13 years, with 30% women. The mean model of end stage liver disease score was 22, and Child-Pugh (CP) scores were C: 41%, B: 33% and A: 26%. The mean Charlson Comorbidity Index was 5.6. Twenty-four (80%) patients had a clinical decompensating event (hepatic encephalopathy, ascites, esophageal varices); the mean hepatic venous pressure gradient was 14.1 mm Hg (n=8). In 33% of patients, LGIB was considered significant bleeding that necessitated blood transfusion. The most common cause of LGIB was hemorrhoids (11 patients, 37%), followed by portal hypertensive enteropathy or colopathy (7 patients, 23%). Hemoglobin levels on admission were lower in patients with CP B/C cirrhosis than in those with CP A (P < 0.001). The length of stay was 9 ± 10 days, and 5 patients died (mortality, 17%). Despite being uncommon, LGIB in cirrhotic patients is associated with a high mortality rate.

Immunological measurement of aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation.

Background/AimsEnzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation.MethodsA total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation.ResultsMETAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation.ConclusionsALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.

Noninvasive Diagnostic Approach By per Rectal Portal Scintigraphy for Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Cell Transplantation

BackgroundSinusoidal obstruction syndrome (SOS) is a significant, potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). In particular, severe SOS frequently causes multiple organ failure and results in poor prognosis. Although early and accurate diagnosis of SOS is vital to intervene early and improve its prognosis, the diagnostic accuracy of clinical criteria, such as the Seattle criteria and Baltimore criteria, is unsatisfactory. Liver biopsy is a gold standard for SOS diagnosis and should be considered to confirm the diagnosis. However, this procedure confers the risk of major bleeding, potentially leading to fatal outcomes, due to low platelet counts or coagulation disorders in patients with SOS. Therefore, a novel, noninvasive diagnostic approach for SOS is needed.The hepatic venous pressure gradient (HVPG) representing portal pressure has been reported to be the most accurate for SOS diagnosis, but its measurement procedure is invasive. Per rectal portal scintigraphy (PRPS), which is a nuclear medicine examination, can estimate portal pressure safely using the portal shunt index (SI) calculated from radioactivity curves of the liver and heart. Only one case report has shown that PRPS was useful to detect portal hypertension in a patient with SOS after allo-HCT (Okamura H, et al. Acta Haematol 2013).To investigate the usefulness of PRPS for SOS diagnosis, we retrospectively analyzed patients who had hepatic disorder and/or ascites after allo-HCT and underwent transjugular liver biopsy and PRPS.MethodsWe examined consecutive patients who underwent transjugular liver biopsy with HVPG measurement and were assessed using PRPS around the same time at our institution between April 2011 and May 2017. When performing transjugular liver biopsy, we also measured the HVPG. All causes of hepatic disorder and/or ascites were pathologically determined based on liver biopsy, if applicable, with autopsy or needle necropsy findings. In PRPS, 370 MBq of Tc-99m pertechnetate was administered to the upper rectum. The SI was calculated using the ratio of liver to heart counts integrated for 24 seconds immediately after the appearance of the liver or heart time-activity curve.We assessed the diagnostic performances of the HVPG and SI for SOS using receiver-operating characteristic (ROC) curves and calculated the optimal cutoff points using the Youden index. Analyses were performed using GraphPad Prism® version 5.02 and SPSS® version 24.ResultsEleven cases were evaluable. The median onset of liver damage and/or ascites was on day 27 after allo-HCT: early-phase (within 30 days) in 7 cases and late-phase (after 30 days) in 4 cases. All patients were histologically diagnosed: 5 with SOS and 6 with non-SOS. The median interval from PRPS to transjagular liver biopsy was +4 days (range, -13 to 15 days). SI values from PRPS correlated with HVPG values in 11 pairs of the measurements (Spearman correlation coefficient 0.92, P < 0.001, Figure 1A).The areas under the ROC curves of the HVPG and SI for SOS diagnosis were 0.85 (95% confidence interval (CI), 0.61-1.0) and 0.77 (95% CI, 0.45-1.0), respectively. The best cutoff values of the HVPG and SI were calculated as 10 mmHg and 56%, respectively. Table 1 shows the sensitivity, specificity, and positive and negative predictive values for the HVPG, SI, and Seattle criteria for SOS diagnosis among all 11 cases.As a subgroup analysis, in 7 patients who developed hepatic disorder and/or ascites in the early phase after allo-HCT, both HVPG and SI were significantly higher in patients with SOS than in those without SOS (mean HVPG: 13.3 mmHg in SOS vs. 4.3 mmHg in non-SOS, P = 0.01, Figure 1B; mean SI: 58% in SOS vs. 26% in non-SOS, P = 0.03, Figure 1C). Furthermore, in these 7 patients, both the HVPG and SI made it possible to completely discriminate between SOS and non-SOS using cutoff points calculated based on the Youden index (8 mmHg for the HVPG and 44% for the SI).ConclusionWe found that the SI from PRPS represented portal pressure, even in patients after allo-HCT, and that the diagnostic accuracy of PRPS for SOS was not only superior to that of the Seattle criteria, but also comparable to that of the HVPG. In addition, especially in the early phase after allo-HCT, SI may be useful to discriminate between SOS and non-SOS. This noninvasive examination could offer a new diagnostic strategy, along with SOS clinical criteria. [Display omitted] DisclosuresHino:Otsuka Pharmaceutical Co., Ltd.: Research Funding; Novartis: Research Funding. Nakamae:Otsuka Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding.

Correlation of baseline Portal pressure (hepatic venous pressure gradient) and Indocyanine Green Clearance Test With Post-transarterial Chemoembolization Acute Hepatic Failure

Liver failure (LF) is a serious complication of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). This could be influenced by the hemodynamic and functional status of the underlying cirrhotic liver. We evaluated baseline hepatic venous pressure gradient (HVPG) and indocyaninegreen (ICG) clearance as predictive factors for the development of LF in patients with liver cirrhosis undergoing TACE for HCC. Forty-two patients with cirrhosis and HCC, referred for TACE, were clinically evaluated including the assessment of Child Turcotte Pugh score (CTP), Model for End-Stage Liver Disease (MELD), HVPGmeasurement, and ICG retention test. Predictors of development of hepatic failure after TACE were determined. In our study population, the mean age of the patients was 58 years, with mean CTP of 6.60±1.149 and mean MELD score of 9.57±2.923. The mean HVPG and ICG retention at 15min was 13.57±4.64mmHg and 21.571±12.434, respectively. Post-TACE Liver Failure (PTLF within 1 month after TACE) developed in 23.80% patients, whereas 76.19% patients did not have PTLF. The statistically significant preprocedure variables that might predict hepatic failure after TACE using univariate analysis were found to be high CTP, MELD score, ICG retention, HVPG, serum bilirubin, serum creatinine, alfa-fetoprotein levels, large tumor size, and low baseline serum albumin. On multivariate analysis, ICG was an independent factor predictive of hepatic failure after TACE. Pretreatment evaluation of routine liver function is of fundamental importance before TACE. Baseline ICG retention test (ICG-R15) is a marker indicating the state of liver function in patients undergoing TACE and is an independent predictor for PTLF. Our study concludes thatwith a cutoff of 25, ICG-R15 has 92.9% accuracy, 90% sensitivity, and 87.5% specificity to predict hepatic failure after TACE.

Shear wave elastography prior to transjugular intrahepatic portosystemic shunt may predict the decrease in hepatic vein pressure gradient.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to treat portal hypertension complications. Our aim was to evaluate liver and spleen stiffness measurement (LSM and SSM, respectively) changes using acoustic radiation force impulse imaging (ARFI) in comparison to Child-Pugh scores for predicting hepatic venous pressure gradient (HVPG) decreases after TIPS implantation. This prospective study included 31 consecutive clinically significant portal hypertension patients with TIPS indication. All patients received LSM and SSM before TIPS, at baseline, 2days (follow-up 1) and 6weeks (follow-up 2) post-implantation. HVPG was performed during the TIPS procedure. The mean decrease in HVPG after TIPS was 63%. LSM and SSM decreased significantly between baseline and follow-up 2 (p < 0.001 and p < 0.001, respectively). At baseline, follow-up 1 and follow-up 2, significant correlations were detected between mean SSM and mean HVPG (p = 0.026; p = 0.018; p = 0.002, respectively). HVPG decreased to ≤ 10mmHg in 61% of patients for which LSM, SSM, and Child-Pugh score were predictors (p = 0.033, p = 0.002 and p = 0.030, respectively). The area under the curve (AUC) for LSM, SSM, and Child-Pugh was 0.88, 0.90, and 0.84, respectively, with close sensitivity and specificity. SSM had the highest diagnostic accuracy for predicting an HVPG decrease to ≤ 10mmHg in comparison to LSM and Child-Pugh score. Spleen stiffness is superior to liver stiffness and Child-Pugh score as a non-invasive surveillance tool for evaluating patients with clinically significant portal hypertension (HVPG ≥ 10mmHg) prior to TIPS.