Surgical strategies to treat portal vein thrombosis during adult liver transplantation.

BACKGROUND: The incidence of portal vein thrombosis (PVT) at the time of liver transplantation (LT) may be variable and underestimated. Therefore, preoperative diagnosis and stratification of its extension is so relevant for adequate surgical planning. Revascularization of the portal vein graft becomes essential for graft and patient survival after LT. Early stages of PVT may be managed with eversion thrombectomy and end-to-end anastomoses. However, severe PVT (grades 3 and 4) poses significant challenges for patients requiring LT, resulting in more complex surgeries and higher complication rates. To address these complexities, various surgical techniques have been developed, including collateral alternative vessel utilization, renoportal anastomoses, mesoportal jump graft placement, cavoportal hemitranspositions, portal vein arterialization, or even multivisceral transplantation. PURPOSE: We herein describe the preoperative surgical planning as well as the different surgical strategies possible to treat portal vein thrombosis during LT. CONCLUSION: A comprehensive preoperative evaluation of PVT is crucial for accurately assessing its extent and severity. This information is vital for proper surgical planning, which ultimately prepares both the surgeon and the patient for potentially complex procedures during LT. The surgical alternatives presented in this technical report offer promising solutions for treating PVT during LT, making it a viable option for selected patients.

Preoperative Predictive Nomogram Based on Alanine Aminotransferase, Prothrombin Time Activity, and Remnant Liver Proportion (APART Score) to Predict Post-Hepatectomy Liver Failure after Major Hepatectomy.

INTRODUCTION: Post-hepatectomy liver failure (PHLF) is a serious complication associated with major hepatectomies. An accurate prediction of PHLF is necessary to determine the feasibility of major hepatectomy. This study aimed to assess the association between PHLF and preoperative laboratory and computed tomography (CT) findings. METHODS: Medical records of 65 patients who underwent major hepatectomy and preoperative CT were retrospectively reviewed. We evaluated future remnant liver volume evaluation models and remnant liver hemodynamics, which were assessed by arterial enhancement fraction (AEF) by using preoperative CT. Variables, including CT findings, were compared between patients with and without PHLF after major hepatectomy, and the preoperative PHLF-predicting nomogram was constructed using multivariate logistic regression. RESULTS: The PHLF group included 21 patients (32.3%). The AEF was not significantly different between the two groups. In the future remnant liver volume evaluation models, future remnant liver proportion (fRLP) had the highest concordance index (C-index) in the receiver operating characteristic curve analysis (C-index, 0.755). Multivariate analysis of preoperative evaluable factors revealed that alanine aminotransferase levels (p = 0.034), prothrombin time activity (p = 0.021), and fRLP (p = 0.012) were independent predictive factors of PHLF. A nomogram (APART score) was constructed using these three factors, with a receiver operating curve showing a C-index of 0.894. According to the APART score, scores of 51-60 indicated moderate risk (40.0%), and scores over 60 indicated a high risk of PHLF (83.3%) (p < 0.001). DISCUSSION: The APART score may help predict PHLF in patients indicated for major hepatectomies.

Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients.

Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.

Improved hemodynamic and liver function in portal hypertensive cirrhotic rats after administration of B. pseudocatenulatum CECT 7765.

PURPOSE: Evaluating whether changes in gut microbiota induced by a bifidobacterial strain may have an effect on the hepatic vascular function in portal hypertensive cirrhotic rats. METHODS: Bile duct ligation (BDL) was performed in rats. A subgroup of animals received B. pseudocatenulatum CECT7765 (109 cfu/daily ig.) for 1 week prior to laparotomy. Hemodynamic, biochemical and inflammatory markers were evaluated. Ileal microbiota composition was identified. Statistical analysis was performed. RESULTS: Sham-operated (n = 6), BDL (n = 6) and BDL treated with bifidobacteria (n = 8) rats were included. B. pseudocatenulatum CECT7765 significantly decreased proteobacteria (p = 0.001) and increased Bacteroidetes (p = 0.001) relative abundance. The bifidobacteria decreased the Firmicutes/Bacteroidetes ratio in the BDL model (p = 0.03). BDL with bifidobacteria vs BDL rats showed: significantly reduced portal vein area, portal flow, congestion index, alkaline phosphatase and total bilirubin, significantly increased serum cytokines and nitric oxide levels, gene expression levels of bile acids receptor FXR and endothelial nitric oxide synthase. Quantitative changes in the Clostridiales and Bacteroidales orders were independently associated with variations in portal vein area and portal flow, while changes in the Proteobacteria phylum were independently associated with congestion. Variations in all liver function markers significantly correlated with total OTUs mainly in the Firmicutes, but only changes in the Clostridiales were independently associated with alkaline phosphatase in the ANCOVA analysis. CONCLUSION: Hemodynamic alterations and liver dysfunction induced by BDL in rats are partially restored after oral administration of B. pseudocatenulatum CECT7765. Results provide a proof-of-concept for the beneficial effect of this bifidobacterial strain in reducing complications derived from portal hypertension in cirrhosis.

Reproducibility study of four-dimensional flow MRI of arterial and portal venous liver hemodynamics: influence of spatio-temporal resolution.

PURPOSE: To evaluate influence of variation in spatio-temporal resolution and scan-rescan reproducibility on three-dimensional (3D) visualization and quantification of arterial and portal venous (PV) liver hemodynamics at four-dimensional (4D) flow MRI. METHODS: Scan-rescan reproducibility of 3D hemodynamic analysis of the liver was evaluated in 10 healthy volunteers using 4D flow MRI at 3T with three different spatio-temporal resolutions (2.4 × 2.0 × 2.4 mm(3), 61.2 ms; 2.5 × 2.0 × 2.4 mm(3), 81.6 ms; 2.6 × 2.5 × 2.6 mm(3), 80 ms) and thus different total scan times. Qualitative flow analysis used 3D streamlines and time-resolved particle traces. Quantitative evaluation was based on maximum and mean velocities, flow volume, and vessel lumen area in the hepatic arterial and PV systems. RESULTS: 4D flow MRI showed good interobserver variability for assessment of arterial and PV liver hemodynamics. 3D flow visualization revealed limitations for the left intrahepatic PV branch. Lower spatio-temporal resolution resulted in underestimation of arterial velocities (mean 15%, P < 0.05). For the PV system, hemodynamic analyses showed significant differences in the velocities for intrahepatic portal vein vessels (P < 0.05). Scan-rescan reproducibility was good except for flow volumes in the arterial system. CONCLUSION: 4D flow MRI for assessment of liver hemodynamics can be performed with low interobserver variability and good reproducibility. Higher spatio-temporal resolution is necessary for complete assessment of the hepatic blood flow required for clinical applications.

Liver fibrosis emulation: Impact of the vascular fibrotic alterations on hemodynamics.

The liver circulatory system comprises two blood supply vascular trees (the hepatic artery and portal venous networks), microcirculation through the hepatic capillaries (the sinusoids), and a blood drainage vascular tree (the hepatic vein network). Vasculature changes due to fibrosis -located predominantly at the microcirculation level- lead to a marked increase in resistance to flow causing an increase in portal pressure (portal hypertension). Here, we present a liver fibrosis/cirrhosis model. We build on our 1D model of the healthy hepatic circulation, which considers the elasticity of the vessels walls and the pulsatile character of blood flow and pressure, and recreate the deteriorated liver vasculature due to fibrosis. We emulate altered sinusoids by fibrous tissue (stiffened, compressed and splitting) and propose boundary conditions to investigate the impact of fibrosis on hemodynamic variables within the organ. We obtain that the sinusoids stiffness leads to changes in the amplitude and shape of the blood flow and pressure waveforms but not in their mean value. For the compressed and splitting sinusoids, we observe significant increases in the mean value and amplitude of the pressure waveform in the altered sinusoids and in the portal venous network. In other words, we obtain the portal hypertension clinically observed in fibrotic/cirrhotic patients. We also study the extent of the spreading fibrosis by performing the structural fibrotic changes in an increasingly number of sinusoids. Finally, we calculate the portal pressure gradient (PPG) in the model and obtain values in agreement with those reported in the literature for fibrotic/cirrhotic patients.

Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension: A case report with 8 years follow-up.

Non-selective beta-blockers are the mainstay of medical therapy for portal hypertension in liver cirrhosis. Inhibitors of phosphodiesterase-5 (PDE-5-inhibitors) reduce portal pressure in the acute setting by > 10% which may suggest a long-term beneficial effect. Currently, there is no available data on long-term treatment of portal hypertension with PDE-5-inhibitors. This case of a patient with liver cirrhosis secondary to autoimmune liver disease with episodes of bleeding from esophageal varices is the first documented case in which a treatment with a PDE-5-inhibitor for eight years was monitored. In the acute setting, the PDE-5-inhibitor Vardenafil lowered portal pressure by 13%. The portal blood flow increased by 28% based on Doppler sonography and by 16% using MRI technique. As maintenance medication the PDE-5-inhibitor Tadalafil was used for eight consecutive years with comparable effects on portal pressure and portal blood flow. There were no recurrence of bleeding and no formation of new varices. Influencing the NO-pathway by the use of PDE-5 inhibitors may have long-term beneficial effects in compensated cirrhosis.

Quantitative PET of liver functions.

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance Kmet (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace Kmet and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

4D flow imaging with MRI.

Magnetic resonance imaging (MRI) has become an important tool for the clinical evaluation of patients with cardiovascular disease. Since its introduction in the late 1980s, 2-dimensional phase contrast MRI (2D PC-MRI) has become a routine part of standard-of-care cardiac MRI for the assessment of regional blood flow in the heart and great vessels. More recently, time-resolved PC-MRI with velocity encoding along all three flow directions and three-dimensional (3D) anatomic coverage (also termed '4D flow MRI') has been developed and applied for the evaluation of cardiovascular hemodynamics in multiple regions of the human body. 4D flow MRI allows for the comprehensive evaluation of complex blood flow patterns by 3D blood flow visualization and flexible retrospective quantification of flow parameters. Recent technical developments, including the utilization of advanced parallel imaging techniques such as k-t GRAPPA, have resulted in reasonable overall scan times, e.g., 8-12 minutes for 4D flow MRI of the aorta and 10-20 minutes for whole heart coverage. As a result, the application of 4D flow MRI in a clinical setting has become more feasible, as documented by an increased number of recent reports on the utility of the technique for the assessment of cardiac and vascular hemodynamics in patient studies. A number of studies have demonstrated the potential of 4D flow MRI to provide an improved assessment of hemodynamics which might aid in the diagnosis and therapeutic management of cardiovascular diseases. The purpose of this review is to describe the methods used for 4D flow MRI acquisition, post-processing and data analysis. In addition, the article provides an overview of the clinical applications of 4D flow MRI and includes a review of applications in the heart, thoracic aorta and hepatic system.