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A 52-year-old male with alcoholic cirrhosis. Spectral analysis of the main portal vein demonstrates alternating hepatopetal and hepatofugal flows in a tachypneic patient, compatible with a toand-fro flow in the main portal vein.
Source publication
Doppler ultrasonography of the hepatic vasculature is an integral part of evaluating precirrhotic and cirrhotic patients. While the reversal of the portal venous flow is a well-recognized phenomenon, other flow patterns, although not as easily understood, may play an important role in assessing the disease status. This article discusses the differe...
Context in source publication
Context 1
... flow can be encountered whereby the nearly stagnant blood column in the portal veins is seen to shift into and out of the liver with the respiratory cycle. The effect of transient flow reversal or cessation of the forward flow during inspiration can be simulated with the Valsalva maneuver, which also results in a transient hepatofugal flow (Fig. 5). With worsening portal hypertension, stagnation of the blood column can lead to thrombosis or progress to a frank flow ...
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Introduction: Non-cirrhotic portal hypertension (NCPH) usually has lower liver stiffness (LS) and hepatic pressure gradient (HPVG), than cirrhosis. At times, it can have elevated LS and HVPG and be confused with liver cirrhosis. In this study we aimed to categorize those entities of NCPH with higher values of LS and HVPG for the prognostic relevanc...
Background
Measurement 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 pressur...
Purpose
Several randomized controlled clinical trials have been conducted to investigate the role of carvedilol and propranolol on the effect of portal pressure in patients with cirrhosis, leading to controversial results. Current meta-analysis was performed to compare the efficacy of the two drugs on portal pressure.
Patients and methods
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Background
Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue.
Methods
Consecutive...
Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are...
Citations
... Specific time constraints for drug absorption from the small intestines and colon, at 5 h and 30 h, respectively, are applied in accord with the literature values [13]. The high blood flow rate in the portal vein (20-40 cm/s) [14] imposes the rapid removal of the absorbed drug molecules towards the liver maintaining sink conditions in the first-order drug transfer; thus, oral drug absorption obeys zero-order kinetics; see Figure 1. Furthermore, the relevant physiologically based finite-time pharmacokinetic (PBFTPK) models were developed and used for the analysis of oral concentration and time data [15]. ...
... A schematic of the drug molecules (solid circles) moving from the small intestine to the portal vein, where a rapid blood flow (20-40 cm/s)[14] maintains sink conditions throughout the drug absorption process. ...
Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug’s gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time (F.A.T.) concept and the relevant physiologically based finite-time pharmacokinetic (PBFTPK) models developed provided a better physiologically sound description of oral drug absorption. Methods: In this study, we re-analyzed, using PBFTPK models, seven data sets of ketoprofen, amplodipine, theophylline (three formulations), and two formulations (reference, test) from a levonorgestrel bioequivalence study. Equations for one-compartment-model drugs, for the estimation of fraction of dose absorbed or the bioavailable fraction exclusively from oral data, were developed. Results: In all cases, meaningful estimates for (i) the number of absorption stages, namely, one for ketoprofen and the levonorgestrel formulations, two for amlodipine, the immediate-release theophylline formulation, and the extended-release Theotrim formulation, and three for the extended-release Theodur formulation, (ii) the duration of each absorption stage and the corresponding drug input rate, and (iii) the total duration of drug absorption, which ranged from 0.75 h (ketoprofen) to 11.6 h for Theodur were derived. Estimates for the bioavailable fraction of ketoprofen and two theophylline formulations exhibiting one-compartment-model kinetics were derived. Conclusions: This study provides insights into the detailed characteristics of oral drug absorption. The use of PBFTPK models in drug absorption analysis can be leveraged as a computational framework to discontinue the perpetuation of the mathematical fallacy of classical pharmacokinetic analysis based on the absorption rate constant as well as in the physiologically based pharmacokinetic (PBPK) studies and pharmacometrics. The present study is an additional piece of evidence for the scientific and regulatory changes required to be implemented by the regulatory agencies in the not-too-distant future.
... Exclusion criteria included the impossibility to obtain an adequate hepatic ultrasound assessment; pregnancy; S-wave reversal in hepatic vein Doppler; confirmed or suspected abdominal hypertension; chronic kidney disease in hemodialysis [17]; patients with limitations of therapeutic effort; Child C cirrhosis [18]; moderate to severe tricuspid regurgitation; cardiac arrhythmias; spontaneous ventilation; extracorporeal life support; severe respiratory failure (PaO 2 :FiO 2 ratio of < 100 mm Hg) and/ or need of PEEP > 15 cm H20. ...
Background
Assessment of dynamic parameters to guide fluid administration is one of the mainstays of current resuscitation strategies. Each test has its own limitations, but passive leg raising (PLR) has emerged as one of the most versatile preload responsiveness tests. However, it requires real-time cardiac output (CO) measurement either through advanced monitoring devices, which are not routinely available, or echocardiography, which is not always feasible. Analysis of the hepatic vein Doppler waveform change, a simpler ultrasound-based assessment, during a dynamic test such as PLR could be useful in predicting preload responsiveness. The objective of this study was to assess the diagnostic accuracy of hepatic vein Doppler S and D-wave velocities during PLR as a predictor of preload responsiveness.
Methods
Prospective observational study conducted in two medical–surgical ICUs in Chile. Patients in circulatory failure and connected to controlled mechanical ventilation were included from August to December 2023. A baseline ultrasound assessment of cardiac function was performed. Then, simultaneously, ultrasound measurements of hepatic vein Doppler S and D waves and cardiac output by continuous pulse contour analysis device were performed during a PLR maneuver.
Results
Thirty-seven patients were analyzed. 63% of the patients were preload responsive defined by a 10% increase in CO after passive leg raising. A 20% increase in the maximum S wave velocity after PLR showed the best diagnostic accuracy with a sensitivity of 69.6% (49.1–84.4) and specificity of 92.8 (68.5–99.6) to detect preload responsiveness, with an area under curve of receiving operator characteristic (AUC–ROC) of 0.82 ± 0.07 ( p = 0.001 vs. AUC–ROC of 0.5). D-wave velocities showed worse diagnostic accuracy.
Conclusions
Hepatic vein Doppler assessment emerges as a novel complementary technique with adequate predictive capacity to identify preload responsiveness in patients in mechanical ventilation and circulatory failure. This technique could become valuable in scenarios of basic hemodynamic monitoring and when echocardiography is not feasible. Future studies should confirm these results.
... Between November 2022 and June 2023, we included consecutive patients aged > 18 years who required invasive mechanical ventilation and vasopressor support. The exclusion criteria were as follows: a) more than 24 h after ICU admission, b) inadequate echographic window precluding adequate ultrasound assessment, c) mechanical circulatory support, d) pregnancy, e) chronic dialysis [29], f ) Child-Pugh C cirrhosis [30], g) prone positioning, and h) any limitation of life support at ICU admission. Eligible patients were assessed at a single time point during the first 24 h after ICU admission, in which fluid responsiveness status and VC signals were measured simultaneously. ...
Background
Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission.
Methods
Multicenter, prospective cross-sectional observational study conducted in three medical–surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected.
Results
Ninety patients were included. Median age was 63 [45–71] years old, and median SOFA score was 9 [7–11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR−). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR− groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals.
Conclusions
Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.
... The Doppler flow pa ern in chronic liver disease exhibits various forms corresponding to the severity of disease. In addition, the Doppler flow of the portal vein is influenced by various factors, such as right heart failure or arteriovenous shunting [33,34]. Liver cirrhosis, in particular, might show diverse pa erns of portal vein flow such as retrograde flow, pulsatile flow, or even antegrade flow with low portal venous velocity, contingent on the presence of portal hypertension or arteriovenous shunts [35]. ...
... The Doppler flow pattern in chronic liver disease exhibits various forms corresponding to the severity of disease. In addition, the Doppler flow of the portal vein is influenced by various factors, such as right heart failure or arteriovenous shunting [33,34]. Liver cirrhosis, in particular, might show diverse patterns of portal vein flow such as retrograde flow, pulsatile flow, or even antegrade flow with low portal venous velocity, contingent on the presence of portal hypertension or arteriovenous shunts [35]. ...
(1) Background: Despite numerous noninvasive methods for assessing liver fibrosis, effective ultrasound parameters remain limited. We aimed to identify easily measurable ultrasound parameters capable of predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and metabolic-dysfunction-associated steatotic liver disease (MASLD); (2) Methods: The data of 994 patients diagnosed with NAFLD via ultrasound at the Armed Forces Goyang Hospital were retrospectively collected from June 2022 to July 2023. A liver stiffness measurement (LSM) ≥ 8.2 kPa was classified as significant fibrosis. Liver steatosis with cardiometabolic risk factors was defined as MASLD. Two ultrasound variables, the portal venous pulsatility index (VPI) and main portal vein diameter (MPVD), were measured; (3) Results: Of 994 patients, 68 had significant fibrosis. Significant differences in VPI (0.27 vs. 0.34, p < 0.001) and MPVD (10.16 mm vs. 8.98 mm, p < 0.001) were observed between the fibrotic and non-fibrotic groups. A logistic analysis adjusted for age and body mass index (BMI) revealed that only VPI (OR of 0.955, p = 0.022, VPI on a 0.01 scale) and MPVD (OR of 1.501, p < 0.001) were significantly associated with significant liver fibrosis. In the MASLD cohort (n = 939), VPI and MPVD were associated with significant fibrosis. To achieve better accuracy in predicting liver fibrosis, we established a nomogram that incorporated MPVD and VPI. The established nomogram was validated in the test cohort, yielding an area under the receiver operating characteristic curve of 0.821 for detecting significant liver fibrosis; (4) Conclusions: VPI and MPVD, as possible surrogate markers, are useful in predicting significant fibrosis in patients with NAFLD and MASLD.
... In severe fatty liver disease leading to cirrhosis, the hepatic parenchymal echotexture might not show clear changes, posing diagnostic challenges. Hemodynamic changes include portal blood vessel dilatation (main vein diameter > 13 mm), decreased portal blood flow rate, altered portal blood flow direction, and changes in hepatic vein blood flow patterns, with observed umbilical vein as lateral blood flow and expanded left gastric vein [15]. As cirrhosis progresses and portal hypertension worsens, intrahepatic blood flow changes, leading to many studies measuring these changes using ultrasound examinations. ...
The ultrasound examination, capable of non-invasively detecting subtle changes in the liver's structure and form, can be extremely helpful. It is not only useful in identifying liver tumors but also in diagnosing and differentiating various liver diseases. Continuous monitoring with ultrasound is especially valuable in patients with chronic hepatitis B and C, as well as other chronic liver diseases, for understanding disease progression and early detection of hepatocellular carcinoma. It is also used in determining the degree of liver fibrosis. Therefore, our goal is to enhance diagnostic capabilities by describing basic ultrasound findings related to diffuse liver diseases.
... Normal portal vein flows (PVF) present with gentle undulations on Doppler assessment, and high portal vein pulsatility is present in arterio-portal shunting, right heart failure, and tricuspid regurgitation. [80] In cardiac surgery, a high portal pulsatility fraction (50%) was shown to be associated with RV dysfunction, leading to venous hypertension and low systemic perfusion, consequently increasing postoperative complications. [81] Also, portal flow pulsatility can predict liver function test abnormalities in patients with congestive heart failure. ...
Orthotopic liver transplantation (OLT) is the standard of care for patients suffering from end stage liver disease (ESLD). This is a high-risk procedure with the potential for hemorrhage, large shifts in preload and afterload, and release of vasoactive mediators that can have profound effects on hemodynamic equilibrium. In addition, patients with ESLD can have preexisting coronary artery disease, cirrhotic cardiomyopathy, porto-pulomary hypertension and imbalanced coagulation. As cardiovascular involvement is invariable and patient are at an appreciable risk of intraoperative cardiac arrest, Trans esophageal echocardiography (TEE) is increasingly becoming a routinely utilized monitor during OLT in patients without contraindications to its use. A comprehensive TEE assessment performed by trained operators provides a wealth of information on baseline cardiac function, while a focused study specific for the ESLD patients can help in prompt diagnosis and treatment of critical events. Future studies utilizing TEE will eventually optimize examination safety, quality, permit patient risk stratification, provide intraoperative guidance, and allow for evaluation of graft vasculature.
... It is worth noting that while portal Doppler remains unaffected by right atrial pressure, a false negative interpretation can occur in the setting of liver Frontiers in Cardiovascular Medicine cirrhosis due to centrilobular fibrosis. Therefore, a scenario of a seemingly normal pattern (pulsatility <30%) can mask hepatic congestion (44). In TR, key intrarenal waveform findings include an elevated x-descent and a significant increase in the v-wave. ...
There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the “forgotten” defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.
... 4 Extrahepatic manifestations on Doppler include features of PHT like enlarged portal vein diameter > 12 mm, decreased portal vein velocity of <16 cm/s (►Fig. 1C; normal velocity is between 20 and 40 cm/s), 5 hepatofugal flow, enlarged and tortuous hepatic artery, 4 splenomegaly, and portosystemic collaterals. Portal vein thrombosis can occur in cirrhosis (prevalence: 0.6-15.8%). ...
... Studies comparing fibrosis staging using ARFI and FibroScan have shown that the accuracy in fibrosis staging using ARFI is similar or better than that of FibroScan. 8,[10][11][12] The update to the Society of Radiologists in Ultrasound (SRU) consensus suggests using a "rule of four" (5,9,13, and 17 kPa) for fibrosis staging with ARFI-based techniques in patients with chronic viral hepatitis or nonalcholic fatty liver disease. 8 ►Table 2 summarizes these cutoff value recommendations. ...
Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices.
... While the relevance of helical or vortical flow in the portal vein remains unknown, studies suggest that portal venous flow is mainly linear or faintly helical. Linear flow can be altered by factors including respiratory variation, portal hypertension, surgery, and vessel diameter and angulation [18,[20][21][22][23]. ...
Purpose
The purpose of this work was to establish normal reference values for 4D flow MRI-derived flow, velocity, and vessel diameters, and to define characteristic flow patterns in the portal venous system of healthy adult subjects.
Methods
For this retrospective study, we screened all available 4D flow MRI exams of the upper abdomen in healthy adults acquired at our institution between 2012 and 2022 at either 1.5 T or 3.0 T MRI after ≥ 5 h fasting. Flow, velocity, and effective diameter were quantified in the 8 planes in the portal venous system (splenic vein, superior mesenteric vein, main, right, and left portal veins). Vessel delineation was manually adjusted over time. Reference ranges for were defined as the mean ± 2 standard deviations. Three readers noted helical and vortical flow on time-resolved pathline visualizations. Conservation of mass flow analysis was performed for quality assurance.
Results
We included 44 healthy subjects (26 female, 18–74 years) in the analysis. We report reference values for mean and peak flow, mean velocity, and vessel diameter in the healthy portal vein using 4D flow MRI. Normal flow patterns in the portal vein included faint helical (66%) or linear flow (34%). Conservation of mass analysis demonstrated a relative error of 1.1 ± 4.6% standard deviation (SD) at the splenomesenteric confluence and − 1.4 ± 4.1% SD at the portal bifurcation.
Conclusion
We have reported normal hemodynamic values that are necessary baseline data for emerging clinical applications of 4D flow MRI in the portal venous system. Results are consistent with previously published values from smaller cohorts.
Graphical abstract
... In fact this is true because drug absorption takes place under sink conditions for physicochemical and physiological reasons. Thus, for BCS class II, III and IV drugs with low solubility and/or low permeability drug concentration in the GI tract remains essentially constant; in parallel, high blood flow in the vena cava, 20-40 cm/s [10] imposes sink conditions for the drug transfer rate. For class I drugs with high solubility and high permeability, absorption is very rapid and is completed in very short time. ...
To date, mechanistic modeling of oral drug absorption has been achieved via the use of physiologically based pharmacokinetic (PBPK) modeling, and more specifically, physiologically based biopharmaceutics model (PBBM). The concept of finite absorption time (FAT) has been developed recently and the application of the relevant physiologically based finite time pharmacokinetic (PBFTPK) models to experimental data provides explicit evidence that drug absorption terminates at a specific time point. In this manuscript, we explored how PBBM and PBFTPK models compare when applied to the same dataset. A set of six compounds with clinical data from immediate-release formulation were selected. Both models resulted in absorption time estimates within the small intestinal transit time, with PBFTPK models generally providing shorter time estimates. A clear relationship between the absorption rate and the product of permeability and luminal concentration was observed, in concurrence with the fundamental assumptions of PBFTPK models. We propose that future research on the synergy between the two modeling approaches can lead to both improvements in the initial parameterization of PBPK/PBBM models but to also expand mechanistic oral absorption concepts to more traditional pharmacometrics applications.
