Portal Pressure Measurements Research Articles

Non-invasive Measurement of Portal Pressure

To provide an updated overview of the existing and emerging non-invasive diagnostic methods to assess portal hypertension. Data on liver stiffness measurement confirmed that it is a mainstay for assessing the risk of clinically significant portal hypertension in patients with advanced chronic liver disease of any etiology. The Baveno criteria for identifying patients who can safely spare endoscopy have been validated in NASH and cholestatic liver disease. New expanded criteria and other simple non-invasive algorithms including MELD score or spleen stiffness have been proposed and can lead to a higher proportion of endoscopies without significantly increasing the risk of missing large esophageal varices. MR and CT improve the anatomical imaging of gastroesophageal varices and abdominal collaterals and dynamic imaging based on MR and able to quantify hepatic blood flow are in development. Contrast-enhanced ultrasound and methacetin breath test are emerging promising methods to estimate the HVPG non-invasively. Several different non-invasive methods are now available and can be used in clinical practice to achieve a successful identification of patients with clinically significant portal hypertension in chronic liver disease. However, an exact estimation of HVPG is not available yet, and changes in portal pressure cannot yet be detected by non-invasive methods.

Endoscopic foregut surgery and interventions: The future is now. The state-of-the-art and my personal journey.

In this paper, I reviewed the emerging field of endoscopic surgery and present data supporting the contention that endoscopy can now be used to treat many foregut diseases that have been traditionally treated surgically. Within each topic, the content will progress as follows: “lessons learned”, “technical considerations” and “future opportunities”. Lessons learned will provide a brief background and update on the most current literature. Technical considerations will include my personal experience, including tips and tricks that I have learned over the years. Finally, future opportunities will address current unmet needs and potential new areas of development. The foregut is defined as “the upper part of the embryonic alimentary canal from which the pharynx, esophagus, lung, stomach, liver, pancreas, and part of the duodenum develop”. Foregut surgery is well established in treating conditions such as gastroesophageal reflux disease (GERD), achalasia, esophageal diverticula, Barrett’s esophagus (BE) and esophageal cancer, stomach cancer, gastric-outlet obstruction, and obesity. Over the past decade, remarkable progress in interventional endoscopy has culminated in the conceptualization and practice of endoscopic foregut surgery for various clinical conditions summarized in this paper. Regarding GERD, there are now several technologies available to effectively treat it and potentially eliminate symptoms, and the need for long-term treatment with proton pump inhibitors. For the first time, fundoplication can be performed without the need for open or laparoscopic surgery. Long-term data going out 5-10 years are now emerging showing extended durability. In respect to achalasia, per-oral endoscopic myotomy (POEM) which was developed in Japan, has become an alternative to the traditional Heller’s myotomy. Recent meta-analysis show that POEM may have better results than Heller, but the issue of post-POEM GERD still needs to be addressed. There is now a resurgence of endoscopic treatment of Zenker’s diverticula with improved technique (Z-POEM) and equipment; thus, patients are choosing flexible endoscopic treatment as opposed to open or rigid endoscopy options. In regard to BE, endoscopic submucosal dissection (ESD) which is well established in Asia, is now becoming more mainstream in the West for the treatment of BE with high grade dysplasia, as well as early esophageal cancer. In combination with all the ablation technologies (radiofrequency ablation, cryotherapy, hybrid argon plasma coagulation), the entire spectrum of Barrett’s and related dysplasia and early cancer can be managed predominantly by endoscopy.Importantly, in regard to early gastric cancer and submucosal tumors (SMTs) of the stomach, ESD and full thickness resection (FTR) can excise these lesions en-bloc and endoscopic suturing is now used to close large defects and perforations. For treatment of patients with malignant gastric outlet obstruction (GOO), endoscopic gastro-jejunostomy is now showing better results than enteral stenting. G-POEM is also emerging as a treatment option for patients with gastroparesis. Obesity has become an epidemic in many western countries and is becoming also prevalent in Asia. Endoscopic sleeve gastroplasty (ESG) is now becoming an established treatment option, especially for obese patients with body mass index between 30 and 35. Data show an average weight loss of 16 kg after ESG with long-term data confirming sustainability. Finally, in respect to endo-hepatology, there are many new endoscopic interventions that have been developed for patients with liver disease. Endoscopic ultrasound (EUS)-guided liver biopsy and EUS-guided portal pressure measurement are exciting new frontiers for the endo-hepatologists.

Carvedilol Ameliorates Intrahepatic Angiogenesis, Sinusoidal Remodeling and Portal Pressure in Cirrhotic Rats.

BackgroundCarvedilol is the first-line drug for the primary prophylaxis of variceal bleeding due to portal hypertension (PHT) in liver cirrhosis. This study aimed to investigate the effects of carvedilol on intrahepatic angiogenesis and sinusoidal remodeling in cirrhotic rats and explore the underlying mechanisms of carvedilol in PHT.Materials/MethodsFor in vivo experiments, carbon tetrachloride was used to induce liver cirrhosis in rats, and carvedilol was simultaneously administered by gavage. The portal pressure was measured in rats, and liver tissues were examined by immunohistochemistry. Sinusoidal remodeling was observed by transmission electron microscopy. For in vitro experiments, the effects of carvedilol on fibronectin (FN) synthesis in human umbilical vein endothelial cells (HUVECs) were explored by quantitative real-time polymerase chain reaction and western blot analysis.ResultsPortal vein pressure measurements showed that carvedilol reduced portal pressure in cirrhotic rats. Immunohistochemistry assays indicated that carvedilol ameliorated intrahepatic angiogenesis. Transmission electron microscopy examination demonstrated that carvedilol improved sinusoidal remodeling. In the in vitro experiments, carvedilol suppressed transforming growth factor β1 (TGFβ1)-induced FN synthesis in HUVECs by inhibition of the TGFβ1/Smads pathway.ConclusionsCarvedilol ameliorated intrahepatic angiogenesis, sinusoidal remodeling and portal pressure in cirrhotic rats. Carvedilol improved sinusoidal remodeling by suppressing FN synthesis in endothelial cells. Carvedilol has potential utility for treating early-stage liver cirrhosis.

An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products.

The gut-blood barrier (GBB) controls the passage of nutrients, bacterial metabolites and drugs from intestinal lumen to the bloodstream. The GBB integrity is disturbed in gastrointestinal, cardiovascular and metabolic diseases, which may result in easier access of biologically active compounds, such as gut bacterial metabolites, to the bloodstream. Thus, the permeability of the GBB may be a marker of both intestinal and extraintestinal diseases. Furthermore, the increased penetration of bacterial metabolites may affect the functioning of the entire organism. Commonly used methods for studying the GBB permeability are performed ex vivo. The accuracy of those methods is limited, because the functioning of the GBB depends on intestinal blood flow. On the other hand, commonly used in vivo methods may be biased by liver and kidney performance, as those methods are based on evaluation of urine or/and peripheral blood concentrations of exogenous markers. Here, we present a direct measurement of GBB permeability in rats using an in vivo method based on portal blood sampling, which preserves intestinal blood flow and is virtually not affected by the liver and kidney function. Polyurethane catheters are inserted into the portal vein and inferior vena cava just above the hepatic veins confluence. Blood is sampled at baseline and after administration of a selected marker into a desired part of the gastrointestinal tract. Here, we present several applications of the method including (1) evaluation of the colon permeability to TMA, a gut bacterial metabolite, (2) evaluation of liver clearance of TMA, and (3) evaluation of a gut-portal blood-liver-peripheral blood pathway of gut bacteria-derived short-chain fatty acids. Furthermore, the protocol may also be used for tracking intestinal absorption and liver metabolism of drugs or for measurements of portal blood pressure.

Portal venous pressure as a predictor of mortality in cirrhotic patients undergoing emergency surgery

Emergency surgery is a risk factor for mortality in cirrhotic patients. Portal hypertension is an essential feature of decompensated cirrhosis. This study aimed to assess the value of portal venous pressure (PVP) measurement in prediction of 1-month mortality in cirrhotic patients undergoing emergency laparotomy. This prospective study included 121 adults with liver cirrhosis subjected to an emergency laparotomy. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score were used for preoperative patient evaluation. PVP was measured directly at the beginning of surgery. Portal hypertension (PHT) is diagnosed when PVP is greater than 12mmHg. The primary outcome measure was the risk of mortality within one month after surgery. PVP ranged from 5 to 27mmHg; 82 patients (67.8%) had PHT. Fifty-five patients (45.5%) died within 1 month. Mortality was significantly associated with increasing CTP Class, MELD score and PHT (p<0.001 for all). PHT predicts mortality with a sensitivity of 83.6% and specificity of 92.8%. PHT was the only independent predictor of mortality (OR: 23.0, 95%CI: 8.9-59.4). In patients with liver cirrhosis, emergency laparotomy carries a substantial risk of mortality within one month. Portal hypertension is an independent predictor of risk of mortality in these patients.

Hemodynamically efficient portal decompression: the concept of competing spontaneous and surgical shunts

Introduction: Temporary portocaval shunt (PCS) has a positive impact on short-term outcomes after liver transplantation (LT). An alternative to this proximal shunt is a distal passive decompression through mesenterico-saphenous shunt (MSS). The goal of this study was to compare the efficiency of spontaneous and surgical distal versus proximal shunts and discuss their respective place during the anhepatic phase in regard to the anatomy of preexisting spontaneous shunts. Method: Patients transplanted in a 2-year period who underwent portal decompression during the anhepatic phase were included. Intraoperative and in-hospital course were compared according to 2 types of surgical decompression techniques: PCS (n = 44) and MSS (n = 77). The impact of spontaneous shunt anatomy on the hemodynamic and metabolic efficiency of surgical shunts using portal pressure and capillary lactate measurements as well as on early graft function were evaluated. Results: MSS and PCS showed a comparable hemodynamic and metabolic efficiency with no significant difference in terms of portal pressure variations and gut lactate production. There was no significant difference in terms of reperfusion syndrome, transfusion rate, renal failure nor early allograft dysfunction (p = 0.956, 0.575, 0.239 and 0.976 respectively). In case of competing shunts (example: PCS and splenorenal shunt or MSS and left gastric shunt), there was a significantly higher rate of EAD (67% vs 13%; p = 0.002). Conclusion: Classical portacaval anastomosis and passive mesenterico-saphenous shunt offer similar hemodynamic and metabolic efficiency without impacting on the outcomes after liver transplantation. Their respective place should be discussed in regard to the anatomy of preexisting portosystemic shunts.

Liver Biopsy

AbstractLiver biopsies are among the most common procedures performed by the interventional radiologist. Liver biopsies may be performed through the percutaneous or transjugular approaches. Ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) may be used for imaging guidance. Transjugular liver biopsies are generally reserved for specific circumstances in which the percutaneous method is associated with increased risk to the patient, such as coagulopathy, or when portal pressure measurements are desired. In addition, endobiliary biopsy through percutaneous transhepatic tracts may be an important means of assessing biliary strictures when the endoscopic route is impossible. This article serves as a general review of the multiple diagnostic hepatic interventions that may be performed by the interventional radiologist.

Endoscopic Ultrasound-Guided Portal Pressure Measurement and Interventions.

A growing number of studies have explored endoscopic ultrasound (EUS)-guided vascular catheterization. Potential clinical applications of EUS-guided portal venous access include angiography, measurement of the portosystemic pressure gradient, EUS-guided transhepatic intrahepatic portosystemic shunt creation and portal vein sampling for the evaluation in gastrointestinal cancer. The following article reviews the different devices and techniques employed in these applications.

Hepatic venous pressure gradient after portal vein embolization: An accurate predictor of future liver remnant hypertrophy

BackgroundThe impact of portal hemodynamic variations after portal vein embolization on liver regeneration remains unknown. We studied the correlation between the parameters of hepatic venous pressure measured before and after portal vein embolization and future hypertrophy of the liver remnant after portal vein embolization. MethodsBetween 2014 and 2017, we reviewed patients who were eligible for major hepatectomy and who had portal vein embolization. Patients had undergone simultaneous measurement of portal venous pressure and hepatic venous pressure gradient before and after portal vein embolization by direct puncture of portal vein and inferior vena cava. We assessed these parameters to predict future liver remnant hypertrophy. ResultsTwenty-six patients were included. After portal vein embolization, median portal venous pressure (range) increased from 15 (9–24) to 19 (10–27) mm Hg and hepatic venous pressure gradient increased from 5 (0–12) to 8 (0–14) mm Hg. Median future liver remnant volume (range) was 513 (299–933) mL before portal vein embolization versus 724 (499–1279) mL 3 weeks after portal vein embolization, representing a 35% (7.4–83.6) median hypertrophy. Post–portal vein embolization hepatic venous pressure gradient was the most accurate parameter to predict failure of future liver remnant to reach a 30% hypertrophy (c-statistic: 0.882 [95% CI: 0.727–1.000], P < 0.001). A cut-off value of post–portal vein embolization hepatic venous pressure gradient of 8 mm Hg showed a sensitivity of 91% (95% CI: 57%–99%), specificity of 80% (95% CI: 52%–96%), positive predictive value of 77% (95% CI: 46%–95%) and negative predictive value of 92.3% (95% CI: 64.0%–99.8%). On multivariate analysis, post–portal vein embolization hepatic venous pressure gradient and previous chemotherapy were identified as predictors of impaired future liver remnant hypertrophy. ConclusionPost–portal vein embolization hepatic venous pressure gradient is a simple and reproducible tool which accurately predicts future liver remnant hypertrophy after portal vein embolization and allows early detection of patients who may benefit from more aggressive procedures inducing future liver remnant hypertrophy. (Surgery 2018;143:1-2.)

Endoscopic Ultrasound for the Hepatologist: A Comprehensive Review.

In the last few years, the diagnostic and therapeutic utilization of endoscopic ultrasound (EUS) for a variety of liver conditions has exponentially grown. We performed a thorough search for all available studies on the performance of diagnostic and therapeutic EUS in the field of hepatology. This article reviews the indication of EUS in the evaluation and treatment of portal hypertension, portal vein pressure measurement, focal liver lesions, and parenchymal liver diseases, and presents all the clinical evidences available so far in this regard. All the review data suggest that EUS is becoming an increasingly important tool in the armamentarium of the hepatologists for the management of certain liver-related conditions. Implementation in the education of the hepatologists of means to become more familiar with both diagnostic and therapeutic capabilities of EUS is warranted.

Portal pressure and liver stiffness measurements in the prediction of fibrosis regression after sustained virological response in recurrent hepatitis C.

In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694).

Endoscopic Ultrasound-Guided Vascular Interventions: From Diagnosis to Treatment.

The development of endoscopic ultrasound was driven by the need to develop less invasive alternatives to surgical and radiologic interventions for a wide variety of gastrointestinal conditions. During the past decade, there has been a very rapid growth in the clinical role and capabilities of endoscopic ultrasound-guided therapeutic interventions. Endoscopic ultrasound offers both real-time imaging and access to structures within and adjacent to the gastrointestinal tract. The proximity of the gastrointestinal system to vascular structures throughout the abdomen and the mediastinum allows for endoscopic ultrasound-guided vascular access and therapy. The recent development of endoscopic ultrasound-guided vascular interventions has relied both on finding new applications for standard endoscopic accessories and on commandeering tools originally developed for use in interventional radiology. This article provides a review of the literature regarding the current state of endoscopic ultrasound for the management of variceal and nonvariceal bleeding, portal vein angiography and pressure measurements, intrahepatic portosystemic shunts, endoscopic ultrasound-guided fine-needle aspiration for portal vein sampling, drug administration and embolization as well as endoscopic ultrasound-guided cardiac access and treatment.

EUS-guided portal pressure measurement (with videos).

A growing number of studies have explored EUS-guided vascular catheterization due to the relative proximity of the gastrointestinal tract to the major blood vessels of the mediastinum and abdomen. In particular, EUS-guided access of the portal vein (PV) may be favorable given the relative difficulty of PV access through standard percutaneous routes. Two major diagnostic applications of EUS-guided vascular access include angiography and assessment of intravascular pressure. This review will outline the different devices and techniques employed to obtain angiographic visualization and/or direct pressure measurements of the portal circulation. Ease of access, safety, and important lessons learned from each approach will be highlighted.

Comparison of physical parameter measurements between peripheral and portal blood samples in patients with portal hypertension.

Measuring portal venous pressure is necessary to examine, diagnose, and treat portal hypertension, but current methods are invasive. This study aimed to determine whether a noninvasive peripheral blood measurement could be used to estimate portal venous pressure by investigating correlations between certain physical parameter measurements in the peripheral blood with those obtained in portal blood samples. A total of 128 peripheral and portal blood samples from patients (n= 128) were analyzed for blood rheology and routine blood parameters. The mean peripheral and portal whole blood viscosities under the shear rates of 200 s-1 (BV 200 s-1) were 2.97 ± 0.50 mPa.s and 3.06 ± 0.39 mPa.s. The mean peripheral and portal BV 30 s-1 values were 3.96 ± 0.79 mPa.s and 4.16 ± 0.64 mPa.s. We observed strong correlations between peripheral and portal blood measurements of BV 200 s-1 (r2= 0.9649), BV 30 s-1 (r2= 0.9622), BV 5 s-1 (r2= 0.9610), and BV 1 s-1 (r2= 0.9623). Our results indicate that peripheral blood can be used to evaluate certain parameters in portal blood for use in biofluid mechanics studies, and to provide noninvasive measurement of portal venous pressure.

Measurement of Portal Pressure and its Application in the Clinical Setting

AbstractPortal hypertension is a severe, yet common sequela of patients with chronic liver disease and is responsible for many of the complications seen in this population. Measurement of the hepatic venous pressure gradient (HVPG) is the current gold standard technique for identifying and evaluating the severity of portal hypertension. Any increase in HVPG to ≥10 mm Hg is considered clinically significant portal hypertension. Above this threshold, complications of portal hypertension begin to manifest. In addition to assessing portal hypertension, various HVPG thresholds have been shown to have strong prognostic value for risk of complications and therapeutic failure, as well as survival in patients with chronic liver disease. These clinical applications include quantification of disease progression and regression in chronic viral hepatitis, acute alcoholic hepatitis, and hepatocellular carcinoma. Other applications include preoperative evaluation of liver resection and transplantation in patients with cirrhosis and hepatocellular carcinoma, assessment of response to therapy for portal hypertension, and identification of the need for transjugular intrahepatic portosystemic shunt (TIPS) revision.

Small-for-flow liver failure after extended hepatectomy: hot questions and an update

Small-for-size liver syndrome and posthepatectomy liver failure remain a major challenge for surgeons. Recently, updates in literature points to describe this two syndrome as two face of the same coin. These syndromes are characterized by hyperbilirubinemia, coagulopathy, hyper-GGT, high portal pressure and flow in liver remnant, occurring within the first postoperative week. It can lead to post-operative sepsis and bleeding, increasing mortality and morbidity. Despite the large experience in the field of transplantation, few studies are focused on small-for-size syndrome after major hepatectomy. For years, scientists were focused on the size of liver remnant, supposing a small liver remnant, in relation with the primary liver size, was the cause of the syndrome. The strategies used to prevent it after transplantation, have however shown a predominant role of high portal pressure and flow, leading to an alteration in functional regeneration of liver parenchyma, as the prevalent mechanism. According to these evidences, we suggest adopting another nomenclature for the two syndromes: small-for-flow-liver failure. In this article, we analyze and summarize different experiences, proposing our inward algorithm, including the role of portal flow and pressure measurements. This review seeks to be an operative instrument for surgeons and hepatologists in an effort to find a common point of view regarding small for flow liver failure and its management strategies.

Endoscopic Ultrasound-guided Portal Venous Access:

Endoscopic ultrasound (EUS) has evolved from a purely diagnostic to an interventional modality offering minimally invasive alternatives to surgical and radiologic interventions. This has led to a rapidly growing interest in EUS-guided vascular interventions. EUS-guided portal venous access is an emerging technique which opens a new arena for interventional vascular EUS. Portal vein can be accessed under EUS guidance with high precision and low risk of complications thus expanding its application for both benign and malignant conditions. Potential applications of EUS-guided portal vein access include: fine needle aspiration of portal vein thrombus and portal venous blood sampling for circulating tumor cells for diagnosis and staging of occult and known malignancies; portal vein angiography, portal pressure measurement, and creation of endoscopic intrahepatic portosystemic shunt; portal vein embolization and targeted drug delivery. This article will review the current literature on EUS-guided portal vein access, its feasibility and safety in animal and human studies, and current diagnostic and therapeutic applications with future directions.

Endoscopic Ultrasound-Guided Direct Portal Pressure Measurement Using a Digital Pressure Wire with Real-Time Remote Display: A Survival Study.

Portal hypertension is necessary for the development of most clinical complications of cirrhosis. We recently reported a novel, endoscopic ultrasound (EUS)-guided technique for direct portal pressure measurements using a digital pressure wire. The aims of this study were to (1) evaluate safety in an animal survival model and (2) compare direct portal vein (PV) versus transhepatic access of a first-order venule. Yorkshire pigs, weighing 40-55 kg. Procedures were performed under general anesthesia. PV was identified using a linear array echoendoscope and accessed with a 22-G fine needle aspiration needle preloaded with a digital pressure wire. Access was confirmed by portal venography. Mean digital pressure measurements were recorded over 30 seconds, and again after accessing a first-order portal venule in a transhepatic manner. Procedure times and video logs were maintained throughout. Animals were survived for 2 weeks. Repeat portal pressure measurements were performed before euthanasia and necropsy. EUS-guided portal pressure measurements ranged from 3 to 11 mm Hg (mean 6.1) and were performed in a mean time of 214 seconds. There was no difference in measurement between the PV and first-order venule, or between baseline and 2-week follow-up. Five of 5 animals survived without incident. On necropsy, there was no evidence of thrombus or hemorrhage. This study represents the first survival study after EUS-guided direct portal pressure measurements using a digital pressure wire. This method appears safe, straightforward, and precise. Measurements of the PV and a first-order portal venule appear equivalent, and serial measurement seems feasible.

Liver Stiffness Measurement in the Prediction of Clinical Significant Portal Hypertension and Related Complications

Hepatic cirrhosis is the end stage of chronic liver disease and leads to portal hypertension (PH) resulting in disease progression manifested with esophageal varices (EV) formation/bleeding, ascites formation and porto-systemic encephalopathy. The detection, prevention and management of portal hypertension and its complication are important for patient with cirrhosis. Hepatic venous pressure gradient (HVPG) has been the standard reference in portal pressure measurement and good predictor of prognosis and therapeutic effects for patients with PH. However, HVPG measurement is an invasive procedure requiring adequate equipment and needing a certain degree of expertise. Liver stiffness (LS) measured with transient elastography is a non-invasive method and in good correlation with portal pressure assessing with HVPG. Although there is also correlation between LS and presence of EV or high-risk EV, it was not as good as that for clinical significant PH. Most studies have demonstrated LS is useful in the prediction of PHT and its complication for patients with hepatic cirrhosis or advanced fibrosis. Clinically significant PH is >90% likely in patients with LS >20-25kPa. A proposed algorithm using LS, platelet count and abdominal sonography provided a useful strategy to detect early PHT. LS-based score incorporating LS, spleen size and platelet count demonstrated to be useful in identifying patients with clinical significant PHT or EV. Braveno VI consensus recommended avoiding screening scope for those patients with LS<20 kPa and platelet count >150000/mm3. Although useful in the EV prediction, LS measurement is not a replacement of scope in the diagnosis of varices for patients with hepatic cirrhosis.

Endoscopic ultrasonography - emerging applications in hepatology.

The inspection of the liver is a valuable part of the upper endoscopic ultrasonography (EUS) studies, regardless of the primary indication for the examination. The detailed images of the liver segments provided by EUS allows the use of this technique in the study of parenchymal liver disease and even in the diagnosis and classification of focal liver lesions. EUS has also emerged as an important tool in understanding the complex collateral circulation in patients with portal hypertension and their clinical and prognostic value. Recently, EUS-guided portal vein catheterization has been performed for direct portal pressure measurement as an alternative method to evaluate portal hemodynamics. In this review, the authors summarize the available evidence regarding the application of EUS to patients with liver diseases and how we can apply it in our current clinical practice.