Sinusoidal Portal Hypertension Research Articles

Hepatic venous pressure gradient evaluates the Scheuer stage of liver fibrosis by transjugular liver biopsy: a multicenter study

BackgroundHepatic venous pressure gradient (HVPG) is the criterion for assessing sinusoidal portal hypertension. Using HVPG to assess the degree of liver fibrosis by transjugular liver biopsy (TJLB) is still being explored, as no data has been shown that portal hypertension may already be present in patients with advanced hepatic fibrosis (Scheuer stage ≥ S3). The objective of this study was to observe whether portal hypertension exists before progressing to cirrhosis (Scheuer stage = S4). MethodsFifty patients who underwent TJLB and HVPG were enrolled. The correlation between Scheuer stage and HVPG was analyzed using the Pearson correlation coefficient, and the ROC curve predicted the diagnostic value of HVPG in patients with hepatic fibrosis. ResultsThe Scheuer stage and HVPG significantly correlated (r = 0.654, p < 0.001). The AUC of HVPG in predicting advanced liver fibrosis was 0.896, and of cirrhosis was 0.810. There were 45 patients with portal hypertension (HVPG> 5 mmHg), 12 with S3, 29 with S4; There were 42 patients with CSPH (HVPG≥ 10 mmHg), 11 with S3, and 29 with S4. ConclusionHVPG is valuable in evaluating the Scheuer stage of liver fibrosis in patients with TJLB. Portal hypertension might already exist before the progression to cirrhosis in some patients.

Agreement between Wedged Hepatic Venous Pressure and Portal Pressure in Hepatic Sinusoidal Obstruction Syndrome.

Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson's correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland-Altman method were performed for agreement evaluation. A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p &lt; 0.001; ICC: 0.90, p &lt; 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p &lt; 0.05). WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation.

S2945 Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3); COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion: VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient’s clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications.Figure 1.: Sinusoidal dilatation and congestion alongside central vein sclerosis. These are common findings of sinusoidal obstruction syndrome on liver biopsy.

Microbiota transplantation in portal hypertension: promises and pitfalls.

In this commentary, we discuss new findings indicating that microbiota transplantation has favorable impact on portal hypertension (PH) in the experimental model of cirrhosis induced by bile duct ligation (BDL) (Huang et al.; Clin Sci (Lond) (2021) 135(24): 2709-2728, doi: 10.1042/CS20210602). Sinusoidal PH is an ominous outcome of advanced chronic liver disease, characterized by increased intrahepatic vascular resistance (IHVR), splanchnic hyperemia, and the development of portosystemic collaterals. In the work of Huang et al., microbiota transplantation not only alleviated splanchnic hyperdynamic circulation by improving vascular responsiveness and decreasing mesenteric angiogenesis, but also reduced blood flow in portosystemic collaterals. Surprisingly, however, microbiota transplantation had no effect on intrahepatic vasoconstriction in this experimental model. We discuss these observations in the context of recent literature showing that manipulation of the gut microbiota (either by transplantation or through the use of probiotics) may improve IHVR, which is one of the earliest abnormalities in the pathogenesis of sinusoidal PH. Further research is needed to explore the specific molecular and cellular targets associated with the correction of dysbiosis in liver disease.

Review on diagnostic criteria of hepatic sinusoidal obstruction syndrome

Hepatic sinusoidal obstruction syndrome (HSOS) is a kind of hepatic vascular disease which is characterized by damage to hepatic sinusoidal endothelial cells, centrilobular hepatic vein and/or interlobular vein, resulting in stenosis or lumen occlusion, hepatic injury and acute sinusoidal portal hypertension. Generally, most patients with HSOS have mild manifestations, but in severely ill patients, the disease can lead to multiple organ dysfunction/failure, and the mortality rate can be as high as 70%-80%. Therefore, it is important to identify and treat HSOS as soon as possible. This paper introduces the current clinical diagnostic criteria of HSOS, including the Modified Seattle and Baltimore Criteria along with "Nanjing Criteria", and reviews their characteristics, scope of application and limitations.

β-Arrestin2 is a critical component of the GPCR–eNOS signalosome

Endothelial cell nitric oxide (NO) synthase (eNOS), the enzyme responsible for synthesis of NO in endothelial cells, is regulated by complex posttranslational mechanisms. Sinusoidal portal hypertension, a disorder characterized by liver sinusoidal endothelial cell (SEC) injury with resultant reduced eNOS activity and NO production within the liver, has been associated with defects in eNOS protein-protein interactions and posttranslational modifications. We and others have previously identified novel eNOS interactors, including G protein-coupled receptor (GPCR) kinase interactor 1 (GIT1), which we found to play an unexpected stimulatory role in GPCR-mediated eNOS signaling. Here we report that β-arrestin 2 (β-Arr2), a canonical GPCR signaling partner, localizes in SECs with eNOS in a GIT1/eNOS/NO signaling module. Most importantly, we show that β-Arr2 stimulates eNOS activity, and that β-Arr2 expression is reduced and formation of the GIT1/eNOS/NO signaling module is interrupted during liver injury. In β-Arr2-deficient mice, bile duct ligation injury (BDL) led to significantly reduced eNOS activity and to a dramatic increase in portal hypertension compared to BDL in wild-type mice. Overexpression of β-Arr2 in injured or β-Arr2-deficient SECs rescued eNOS function by increasing eNOS complex formation and NO production. We also found that β-Arr2-mediated GIT1/eNOS complex formation is dependent on Erk1/2 and Src, two kinases known to interact with and be activated by β-Arr2 in response to GCPR activation. Our data emphasize that β-Arr2 is an integral component of the GIT1/eNOS/NO signaling pathway and have implications for the pathogenesis of sinusoidal portal hypertension.

Matrix Fibrous Proteins and Cells in Central Vein Fibrosis of Cadaveric Livers

The central vein (CV) is defined as a hepatic vein at the center of the classic liver lobule. It has a cross‐sectional diameter not exceeding 125 μm. The endothelium lining of the vein is thin and has openings that drain every sinusoid of a liver lobule. The rim or wall of the CV is less than 2 μm in thickness with sparse matrix fibrous proteins and cells. Fibrosis of the CV (CVF), also is called perivenular fibrosis, is marked by thickening of the rim of the vein. The fibrotic tissue deposited in the CV may act like a “pervenular fibrous dam” that obliterates the sinusoidal openings into the vein, resulting in sinusoidal portal hypertension. CVF occurs early in hepatic fibrogenesis of rats induced by CCl4 or porcine serum administration. CVF often accompanies perisinusoidal fibrosis of the centrilobular area in alcoholic liver disease and nonalcoholic fatty liver disease. In the liver of elderly cadavers (mean age, 82.1±10.4), we have observed a 49.2 % incidence (31/63 livers) of CVF, but the matrix components of the fibrotic veins are not fully characterized. This study assessed fibrous proteins and cells in CVF of cadaveric livers. A total of 72 fibrotic veins out of 315 veins from 63 livers were studied. The diameters of the veins ranged from 25.4 to 123.7 μm (mean, 75.5 ± 18.3 μm). CVF was considered present when the rim thickness exceeded 9 μm (determined on Sirius red stained sections) coincident with fibrous tissue extension into the perivenous parenchyma. Immunoperoxidase staining revealed that the CV endothelium was positive for factor VIII‐related antigen, a vascular endothelial phenotypic marker. It also stained for CD31 and D34. Staining of basement membrane collagen IV was continuous around the CV endothelium, while laminin, another principal basement membrane protein, was not detected in the CV matrix. Thus, the CV appeared to lack a continuous endothelial basement membrane and a diffusion barrier between the CV circulation and perivenous parenchyma. Fibrillar collagens I, III and V and filamentous collagen VI were robust in the rim of the fibrotic vein. The codistribution of these collagens rendered thickening of the CV as well as provided strength to the CV matrix scaffold. Elastic fibers were noted occasionally among collagen bundles. Myofibroblasts, identified by a‐smooth muscle actin, were the dominant fibrogenic cells producing the fibrous matrix. Few mononuclear cells were also present. The deposition of collagenous fibrous tissue in the rim could occlude the CV endothelial openings, reducing the efficiency and increasing the resistance of sinusoidal blood flow into the CV. This may cause sinusoidal hypertension, impair hepatocyte functions and enhance disease susceptibility of the aged people.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Transient Elastography Anticipates the Diagnosis of VOD/SOS after Adult Allogeneic Stem Cell Transplant: Results from a Prospective Study

Transient Elastography Anticipates the Diagnosis of VOD/SOS after Adult Allogeneic Stem Cell Transplant: Results from a Prospective Study

Biology of portal hypertension.

Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

A computational model of the hepatic circulation applied to analyze the sensitivity of hepatic venous pressure gradient (HVPG) in liver cirrhosis

Measurement of hepatic venous pressure gradient (HVPG) is currently widely adopted to provide an estimate of portal pressure gradient (PPG) in the diagnosis and treatment of portal hypertension associated with liver cirrhosis. Despite the well-documented clinical utility of HVPG, it remains poorly understood how the relationship between HVPG and PPG is affected by factors involved in the pathogenesis and progression of cirrhosis. In the study, a computational model of the hepatic circulation calibrated to in vivo data was developed to simulate the procedure of HVPG measurement and quantitatively investigate the error of HVPG relative to PPG under various pathophysiological conditions. Obtained results confirmed the clinical consensus that HVPG is applicable to the assessment of portal hypertension caused by increased vascular resistance located primarily at the sinusoidal and postsinusoidal sites rather than at the presinusoidal site. On the other hand, our study demonstrated that the accuracy of HVPG measurement was influenced by many factors related to hepatic hemodynamics even in the case of sinusoidal portal hypertension. For instance, varying presinusoidal portal vascular resistance significantly altered the difference between HVPG and PPG, while an enhancement in portosystemic collateral flow tended to improve the accuracy of HVPG measurement. Moreover, it was found that presinusoidal and postsinusoidal vascular resistances interfered with each other with respect to their influence on HVPG measurement. These findings suggest that one should take into account patient-specific pathological conditions in order to achieve a better understanding and utilization of HVPG in the clinical practice.

Heparin-Induced Thrombotic Thrombocytopenia in Budd-Chiari Syndrome: Anticoagulation of Choice?

Budd Chiari Syndrome (BCS) is characterized by hepatic venous outflow tract obstruction leading to post sinusoidal portal hypertension. If untreated, BCS is often fatal. Guidelines recommend heparin and its derivatives for anticoagulation (AC) in BCS. A 23 year-old Caucasian female with no medical history presented with a ten day history of abdominal pain and worsening distension. She reported occasional alcohol use and a remote history of oral contraceptive use 2 years back. She denied a personal and family history of liver disease and hypercoagulable disorders. Laboratory tests showed Hgb of 16.7 gm/dl, WBC of 18.9K, platelet of 525K, AST of 733 U/L, ALT of 889 U/L, AP of 162 U/L, total bilirubin of 3.6 mg/dl, and INR of 1.42. Doppler ultrasound (US) of the liver showed occlusion of the hepatic veins, hepato-splenomegaly and ascites. Contrast-enhanced computed tomography (CECT) confirmed these findings and showed patent but dilated (1.4 cm) portal vasculature and collaterals suggestive of portal hypertension. She was started on intravenous heparin and underwent Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement with a final gradient of 5mmHg. Her liver enzymes initially improved, but began to worsen 8 days later. She developed marked thrombocytopenia and abdominal ecchymosis with eschar (Figure 1). A repeat US Doppler showed decreased flow within TIPS (Figure 2) and new portal vein thrombosis. Positive immunoassay for heparin antibodies confirmed Heparin Induced Thrombotic Thrombocytopenia (HITT). Anticoagulation was changed to bivalirudin and she underwent TIPS revision with thrombectomy. Hypercoagulable work up revealed JAK2-V617F mutation suggestive of myeloproliferative processes- Polycythemia Vera (PCV) and Essential Thrombocythemia (ET). The incidence of BCS is 0.2-0.8 per million/year, however the mortality in untreated BCS is 80-90%. Most BCS cases are acquired and up to 84% of cases have thrombotic diathesis, the most common being PCV and/or ET. Aside from TIPS and liver transplantation, initial AC with heparin is the standard of care. The overall prevalence of HITT from all use is low at 0.2-5.2%. However, in a retrospective study, 9/32 (28%) patients with BCS developed HITT. Our patient initially responded to heparin, but later had extension of thrombosis. This raises the question of alternative anticoagulation such as Direct Thrombin inhibitors in this patient population.Figure: Abdominal eschar due to HITT.Figure: Clotted TIPS - pre and post IR revision.Figure: US doppler showing clotted TIPS.

Nodular Regenerative Hyperplasia

A 38-year-old man with a history of two kidney transplants as well as genotype 3A hepatitis C virus (HCV) without cirrhosis presented with hematemesis. The patient was a nonresponder to pegylated IFN and ribavirin. A transjugular liver biopsy 2 years prior revealed stage 0 fibrosis without portal hypertension (HVPG=2 mm Hg). The patient completed a 12-week course of daclatasvir, sofosbuvir, and ribavirin, and achieved viral eradication with SVR12. Following HCV eradication, the patient developed new-onset ascites. Abdominal ultrasound revealed nodular-appearing liver and moderate ascites. Diagnostic paracentesis showed SAAG > 1.1 with low total protein (< 1.0 g/dL) and no evidence of SBP. He presented after one episode of hematemesis and was found to have a hemoglobin of 6.7 g/dL (baseline 10 g/dL). Emergent EGD revealed new medium-sized esophageal varices that were banded. Despite octreotide infusion, he developed recurrent hematemesis on hospital day 2. Repeat EGD revealed evidence of recurrent variceal bleeding. Liver biopsy demonstrated sinusoidal portal hypertension (HVPG=13 mm Hg) and nodular regenerative hyperplasia of the liver. He underwent TIPS insertion for recurrent variceal bleed with significant reduction in portal pressure gradient and resolution of bleeding. Nodular regenerative hyperplasia (NRH) is a form of noncirrhotic portal hypertension (NCPH). Histologically, NRH is distinguished from other causes of NCPH by diffuse parenchymal regenerative nodules and an absence of or minimal fibrosis in the perisinusoidal/periportal regions. The exact pathophysiology is not clearly defined; however, a generally accepted hypothesis involves hepatocyte hyperplasia in response to chronic inflammation, vascular disease, or direct endothelial injury from drugs, autoantibodies, T-cells, malignancies, or viruses. Development of NRH typically occurs within 1 to 6 years of insult, with some cases reporting development of NRH as early as 5-6 months after exposure toxic agents (i.e. azathioprine, oxaliplatin). Treatment involves avoiding and/or discontinuing offending agents and management of portal hypertension. While NRH is a rare but known complication of solid organ transplantation, it has yet to be reported following successful HCV therapy with direct-acting antiviral agents. In conclusion, we report a novel case of clinically significant NCPH secondary to NRH that developed in a kidney transplant recipient immediately following eradication of HCV.

Ascitis Secondary to Budd Chiari Syndrome Managed By Endovascular Stenting

Introduction Budd-Chiari syndrome (BCS) is an uncommon condition characterized by obstruction of the hepatic venous outflow. Presentation varies from a completely asymptomatic condition to fulminant liver failure 1. BCS is an example of post sinusoidal portal hypertension. The management can be divided into three main categories: medical, surgical, and endovascular 2 . The purpose of this article is to present a case of BCS with ascites managed by endovascular stenting.

Effect of glucocerebrosidase (GC) deficiency in osteoblasts on mineralization and osteoclastogenesis: Implications for bone pathology in Gaucher disease

Gaucher disease (GD) is one of the most common lysosomal diseases. It results from deficiency of the lysosomal enzyme glucocerebrosidase, which leads to accumulation of glucocerebroside and other glycolipids within the lysosomes of macrophages. Regarding liver involvement, hepatomegaly is universal and hepatic fibrosis typically occurs. Later in the disease, sinusoidal portal hypertension can be seen, but cirrhosis and hepatic failure are rare. Metabolic disorders are also common, and during enzymatic replacement therapy are characterized by hypometabolism and reduced levels of adiponectin which can be a risk factor for steatohepatitis. Transitory elastography (TE) is a novel non-invasive method for the assessment of hepatic fibrosis, by measuring liver stiffness. Controlled attenuation parameter (CAP), evaluated with transient elastography, is an efficient method to detect steatosis and define its grades. The AST-to-platelet ratio (APRI) can also be used to estimate fibrosis grade. For predicting significant fibrosis, an APRI cut-off of 0.7 had a sensitivity of 77% and a specificity of 72%. It was most studied in patients with hepatitis C. The aim of this study was to evaluate the hepatic involvement in a group of patients with GD, measuring fibrosis and steatosis by TE with CAP. We also compared the TE results with APRI index. Ten patients in treatment with taliglucerase were included. In 7 patients, TE values were compatible with fibrosis F0/F2 (lower than 9.5 kPA) and the APRI was lower than 0.7. In 2 patients, values were compatible with advanced fibrosis F4 (upper than 12.5 kPA) and APRI was higher than 0.7. In one patient, in whom the TE was difficult to perform because of obesity, there was a discordance between TE that was compatible with fibrosis (F0/F1) and the APRI (which was higher than 0.7). Concerning CAP values, 7 patients had values compatible with low, less than 11%, of steatosis. Two had values compatible with steatosis between 33–66% and 1 had a value compatiblewith steatosis greater than 67%. Therewas no correlation between fibrosis grade and values of CAP. None of the patients had values of transaminases higher than 2 times the upper limit value. TE with CAP can be a valuable tool to evaluate hepatic involvement in GD patients, and in this small sample had a good correlation with APRI index. Studies with larger numbers of subjects should be done to confirm this inference.

Use of bevacizumab to reduce the rate of oxaliplatin-induced thrombocytopenia and splenomegaly.

564 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. In the NSABP C-08 study a reduced rate of thrombocytopenia (1.4% vs 3.4%, P &lt;0.01) was seen in the bevacizumab arm. Evidence suggests that bevacizumab may protect against HSI, though the clinical impact of this has not been well examined. Methods: A retrospective review of metastatic colorectal cancer patients treated at MD Anderson Cancer Center from 1/2003 to 1/2010 with ≥3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab was conducted. Presence of known liver disease, prior liver surgery, absence of spleen, or adjuvant oxaliplatin were exclusion criteria. Splenic volumes pre, during, and post FOLFOX treatment were determined from CT scans and correlated with platelet counts and treatment. Results: 184 pts (138 FOLFOX/Bev; 46 FOLFOX) were identified. The median number of cycles (9 for each cohort) and the total oxaliplatin dose (P = 0.78) did not differ between the two cohorts. The development of splenomegaly (spleen volume increase of ≥30%) was more common in the non-Bev cohort, 48% vs 32%, P=0.013. The median time to splenomegaly was longer in the Bev cohort, 7.6 vs 5.5 months, P=0.023. When comparing patients with and without splenomegaly, the presence of splenomegaly correlated with thrombocytopenia (&lt;150 platelet count) at 3 months (40% vs. 16%, P=0.0005) and beyond (lower mean platelet counts during 3 to 6 months of treatment, P &lt;0.0001 by Two-way ANOVA). A correlation with thrombocytopenia was also seen in the non-Bev vs. Bev cohort at both 3 months (43% vs 24%, P = 0.006) and beyond (P = 0.003). Conclusions: The addition of bevacizumab to oxaliplatin chemotherapy reduces the frequency of splenic enlargement, which directly correlates with a reduced rate of thrombocytopenia. Further study to understand the hepato-protective mechanism of anti-VEGF therapy is needed.

Prospective Study Comparing Different Indirect Methods to Measure Portal Pressure

Purpose To compare the accuracy of wedged hepatic venous pressure (WHVP) measurement with use of an end-hole catheter or an occlusion-balloon catheter versus direct portal pressure (PP) measurement in patients with cirrhosis with sinusoidal portal hypertension and to investigate the factors that affect the results of these indirect measurements. Materials and Methods In a cohort of 174 patients with cirrhosis referred for transjugular intrahepatic portosystemic shunt creation, indirect PP was measured with an end-hole catheter and an occlusion-balloon catheter placed in the right hepatic vein. Direct PP was measured by a pigtail catheter in the main branch of the portal vein. Results PP was more accurately estimated by the occlusion-balloon technique: mean WHVP measurements were 25.5 mm Hg ± 7.9 and 30.6 mm Hg ± 13.9, respectively, for the occlusion-balloon and end-hole catheter techniques, and the direct PP measurement was 25.0 mm Hg ± 7.0. The median absolute differences between direct and the indirect methods were 6.0 mm Hg with the end-hole catheter and 2.0 mm Hg with the occlusion-balloon catheter ( P < .0001, signed-rank test). Relative to direct PP measurements, the occlusion-balloon technique overestimated pressures in cases of higher Model for End-Stage Liver Disease (MELD) scores (Spearman ρ = −0.24; P = .0005). Conclusions Compared with direct PP measurements, agreement was clearly higher for indirect WHVP measurement with occlusion-balloon catheters versus end-hole catheters. However, in patients with a high MELD score, there was an overestimation of PP with the occlusion-balloon method.

Invited Commentary

First, I would like to thank Dr. Haskal for asking me to comment on this important and timely article. Prospective Study Comparing Different Indirect Methods to Measure Portal PressureJournal of Vascular and Interventional RadiologyVol. 22Issue 11PreviewTo compare the accuracy of wedged hepatic venous pressure (WHVP) measurement with use of an end-hole catheter or an occlusion-balloon catheter versus direct portal pressure (PP) measurement in patients with cirrhosis with sinusoidal portal hypertension and to investigate the factors that affect the results of these indirect measurements. Full-Text PDF

OP10 Relaxin inhibits human myofibroblast contractility and modulates portal hypertension in vivo

IntroductionThe peptide hormone relaxin (H2-RLN) has a broad range of biological activities including antifibrotic, anti-inflammatory and haemodynamic effects in a range of target tissues. Increased intrahepatic vascular resistance in cirrhosis...

Pharmacological effects are model specific in animal models of portal hypertension

Pharmacological effects are model specific in animal models of portal hypertension

Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model.

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.