SerpinB3 as hepatic marker of post-resective shear stress.

Post-resective liver failure is a frequent complication of liver surgery and it is due to portal hyperperfusion of the remnant liver and to arterial vasoconstriction, as buffer response of the hepatic artery. In this context, splenectomy allows a reduction of portal flow and increases the survival chance in preclinical models. SerpinB3 is over-expressed in the liver in oxidative stress conditions, as a mechanism of cell defense to provide survival by apoptosis inhibition and cell proliferation. In this study, the expression of SerpinB3 was assessed as predictor of liver damage in in vivo models of major hepatic resection with or without splenectomy. Wistar male rats were divided into 4 groups: group A received 30% hepatic resection, group B > 60% resection, group C > 60% resection with splenectomy and group D sham-operated. Before and after surgery liver function tests, echo Doppler ultrasound and gene expression were assessed. Transaminase values and ammonium were significantly higher in groups that underwent major hepatic resection. Echo Doppler ultrasound showed the highest portal flow and resistance of the hepatic artery in the group with > 60% hepatectomy without splenectomy, while the association of splenectomy determined no increase in portal flow and hepatic artery resistance. Only the group of rats without splenectomy showed higher shear-stress conditions, reflected by higher levels of HO-1, Nox1 and of Serpinb3, the latter associated with an increase of IL-6. In conclusion, splenectomy controls inflammation and oxidative damage, preventing the expression of Serpinb3. Therefore, SerpinB3 can be considered as a marker of post-resective shear stress.

Technical challenges in LDLT - Overcoming small for size syndrome and venous outflow reconstruction.

Living Donor Liver Transplantation (LDLT) emerged as an alternative treatment option for patients with end-stage liver disease waiting for an organ from a deceased donor. In addition to allowing for a faster access to transplantation, LDLT provides improved recipient outcomes when compared to deceased donor LT. However, it represents a more complex and demanding procedure for the transplant surgeon. In addition to a comprehensive preoperative donor assessment and stringent technical considerations during the donor hepatectomy to ensure upmost donor safety, the recipient procedure also comes with intrinsic challenges during LDLT. A proper approach during both procedures will result in favorable donor and recipient's outcomes. Hence, it is critical for the transplant surgeon to know how to overcome such technical challenges and avoid deleterious complications. One of the most feared complications following LDLT is small-for-size syndrome (SFSS). Although, surgical advances and deeper understanding of the pathophysiology behind SFSS has allowed for a safer implementation of LDLT, there is currently no consensus on the best strategy to prevent or manage this complication. Therefore, we aim to review current practices in technically challenging situations during LDLT, with a particular focus on management of small grafts and venous outflow reconstructions, as they possess one of the biggest technical challenges faced during LDLT.

In silico modeling for the hepatic circulation and transport: From the liver organ to lobules.

The function of the liver depends critically on its blood supply. Numerous in silico models have been developed to study various aspects of the hepatic circulation, including not only the macro-hemodynamics at the organ level, but also the microcirculation at the lobular level. In addition, computational models of blood flow and bile flow have been used to study the transport, metabolism, and clearance of drugs in pharmacokinetic studies. These in silico models aim to provide insights into the liver organ function under both healthy and diseased states, and to assist quantitative analysis for surgical planning and postsurgery treatment. The purpose of this review is to provide an update on state-of-the-art in silico models of the hepatic circulation and transport processes. We introduce the numerical methods and the physiological background of these models. We also discuss multiscale frameworks that have been proposed for the liver, and their linkage with the large context of systems biology, systems pharmacology, and the Physiome project. This article is categorized under: Metabolic Diseases > Computational Models Metabolic Diseases > Biomedical Engineering Cardiovascular Diseases > Computational Models.

Hepatic blood flow regulation but not oxygen extraction capability is impaired in prolonged experimental abdominal sepsis.

Impaired oxygen utilization has been proposed to play a significant role in sepsis-induced liver dysfunction, but its magnitude and temporal course during prolonged resuscitation is controversial. The aim of this study is to evaluate the capability of the liver to increase oxygen extraction in sepsis during repeated acute portal vein blood flow reduction. Twenty anesthetized and mechanically ventilated pigs with hepatic hemodynamic monitoring were randomized to fecal peritonitis or controls (n = 10, each). After 8-h untreated sepsis, the animals were resuscitated for three days. The ability to increase hepatic O2 extraction was evaluated by repeated, acute decreases in hepatic oxygen delivery (Do2) via reduction of portal flow. Blood samples for liver function and liver biopsies were obtained repeatedly. Although liver function tests, ATP content, and Do2 remained unaltered, there were signs of liver injury in blood samples and overt liver cell necrosis in biopsies. With acute portal vein occlusion, hepatic Do2 decreased more in septic animals compared with controls [max. decrease: 1.66 ± 0.68 mL/min/kg in sepsis vs. 1.19 ± 0.42 mL/min/kg in controls; portal venous flow (Qpv) reduction-sepsis interaction: P = 0.028]. Hepatic arterial buffer response (HABR) was impaired but recovered after 3-day resuscitation, whereas hepatic oxygen extraction increased similarly during the procedures in both groups (max. increase: 0.27 ± 0.13 in sepsis vs. 0.18 ± 0.09 in controls; all P > 0.05). Our data indicate maintained capacity of the liver to acutely increase O2 extraction, whereas blood flow regulation is transiently impaired with the potential to contribute to liver injury in sepsis.NEW & NOTEWORTHY The capacity to acutely increase hepatic O2 extraction with portal flow reduction is maintained in sepsis with accompanying liver injury, but hepatic blood flow regulation is impaired.

Effect of norepinephrine infusion on hepatic blood flow and its interaction with somatostatin: an observational cohort study.

BACKGROUND: Norepinephrine (NE) is a α1-adrenergic mediated vasopressor and a key player in the treatment of perioperative hypotension. Apart from modulating systemic hemodynamics, NE may also affect regional blood flow, such as the hepatic circulation, which contains a wide variety of adrenergic receptors. It may alter regional vascular tonus and hepatic blood flow (HBF) by reducing portal vein flow (PVF) or hepatic arterial flow (HAF). The aim of this study was to assess the effects of NE on HBF. METHODS: Patients scheduled for pancreaticoduodenectomy were included. All patients received standardized anesthetic care using propofol and remifentanil and were hemodynamically stabilized using a goal-directed hemodynamic strategy guided by Pulsioflex™. On surgical indication, somatostatin (SOMATO) was given to reduce pancreatic secretion. HBF measurements were performed using transit-time ultrasound (Medistim™). Baseline hemodynamic and HBF measurements were made after pancreatectomy, at T1. Afterwards, NE infusion was initiated to increase mean arterial pressure (MAP) by 10 - 20% of baseline MAP (T2) and by 20 - 30% of baseline MAP (T3). HBF and hemodynamic measurements were performed simultaneously at these three time-points. RESULTS: A total of 28 patients were analyzed. Administration of NE significantly increased MAP but had no effect on cardiac index. NE infusion reduced total HBF in all patients (p < 0.01) by a reduction HAF (p < 0.01), while the effect on PVF remained unclear. Post-hoc analysis showed that SOMATO-treated patients had a significant lower PVF at baseline (p < 0.05), which did not change during NE infusion. In these patients, reduction of total HBF was primarily related to a reduction of HAF (p < 0.01). In untreated patients, NE infusion reduced total HBF both by a reduction HAF (p < 0.01) and PVF (p < 0.05). CONCLUSION: Administration of NE reduced total HBF, by decreasing HAF, while the effect on PVF remained unclear. SOMATO-treated patients had a lower PVF at baseline, which remained unaffected during NE infusion. In these patients the decrease in total HBF with NE was entirely related to the decrease in HAF. In SOMATO-untreated patients PVF also significantly decreased with NE. TRIAL REGISTRATION: Study protocol EC: 2019/0395. EudraCT n°: 2018-004,139-66 (25 - 03 - 2019). Clin.trail.gov: NCT03965117 (28 - 05 - 2019).

Effect of meal intake for evaluating hepatic artery by Doppler ultrasonography in liver transplants: Does fasting matter for screening hepatic artery due to hemodynamic changes in splanchnic circulation?

PURPOSE: The aim of this study is to assess the utility of fasting on Doppler ultrasonography findings of hepatic artery in liver transplants. METHODS: Liver transplant patients without vascular abnormalities were prospectively evaluated between December 2017 and January 2020. Doppler sonography was used to describe hemodynamic changes in response to a standard meal. The diameter, peak systolic velocity, blood flow, resistive index (RI) of the main hepatic artery and portal vein peak velocity were measured. RESULTS: The mean hepatic arterial diameter of 44 patients was higher in the fasting group (4.5 mm) than in the postprandial group (3.3 mm) (p < .05). The mean hepatic arterial blood flow decreased (from .276 to .127 L/min) and hepatic arterial RI increased (from .66 to .71) following meal ingestion (p < .05). Hepatic arterial velocity was significantly lower and portal venous velocity was higher after oral intake. CONCLUSION: Meal ingestion has an important effect on hepatic artery Doppler features in liver transplants. Therefore, Doppler ultrasound evaluation should be considered after appropriate fasting due to postprandial responses of liver transplant.

Morphometric analysis of the human common hepatic artery reveals a rich and accessible target for sympathetic liver denervation.

This study quantified the distribution of nerves and adjacent anatomies surrounding human common hepatic artery (CHA) as guidance for catheter based denervation. CHA collected from cadaveric human donors (n = 20) were histologically evaluated and periarterial dimensions and distributions of nerves, lymph nodes, pancreas and blood vessels quantified by digital morphometry. Nerve abundance decreased significantly with distance from the aortic ostium (P < 0.0001) and was higher in the Superior/Inferior compared to the Anterior/Posterior quadrants (P = 0.014). In each locational group, nerves were absent from the artery wall, and starting 0.5-1.0 mm from the lumen exhibited a first order dependence on radial distance, fully defined by the median distance. Median subject-averaged nerve distance to the lumen was 2.75 mm, ranging from 2.1-3.1 mm in different arterial segments and quadrants and 2.0-3.5 mm in individuals. Inter-individual variance was high, with certain individuals exhibiting 50th and 75th nerve distances of, respectively, 3.5 and 6.5 mm The pancreas rarely approached within 4 mm of the lumen proximally and 2.5 mm more distally. The data indicate that the CHA is a rich and accessible target for sympathetic denervation regardless of sex and diabetes, with efficacy and safety most optimally balanced proximally.

The within-individual reproducibility of the disease severity index from the HepQuant SHUNT test of liver function and physiology.

The HepQuant SHUNT test quantifies liver function and blood flow using systemic and portal clearances of cholate. The test can identify the risk of well-compensated patients to develop complications of cirrhosis. To confirm the reliability of a single HepQuant SHUNT test we defined its within-individual reproducibility. Healthy subjects (n = 16), 16 with nonalcoholic steatohepatitis (NASH), and 16 with chronic hepatitis C virus (HCV) underwent 3 HepQuant SHUNT tests on 3 separate days within 30 days. The test involves simultaneous administration of 20 mg 13C-cholate IV and 40 mg d4-cholate PO, and subsequent collection of 3 mL blood samples at 5, 20, 45, 60, and 90 minutes. Clearances are expressed as systemic and portal hepatic filtration rate. Portal-systemic shunting (SHUNT), a disease severity index (DSI), and an estimate of DSI (STAT) are calculated from the clearances. Reproducibility was determined by the intraclass correlation coefficient (ICC > 0.70) and Bland-Altman analysis. Equal numbers of NASH and HCV patients had either early (F0-F2) or advanced (F3/F4) stages of fibrosis. All F3/F4 subjects were clinically compensated. The intraclass correlation coefficient (ICC) for DSI was 0.94 (0.90-0.96 95% confidence interval) indicating excellent reproducibility. The other test parameters had ICCs ranging from 0.74 (SHUNT) to 0.90 (STAT). In Bland-Altman analysis, the mean of differences between measurements of DSI was 0.13 with standard deviation 2.12. The excellent reproducibility of the HepQuant SHUNT test, particularly DSI, supports the use this minimally invasive, blood-based test as a reliable test of liver function and physiology.

Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum.

Intestinal permeability is a critical factor for orally administered drugs. It can be facilitated by uptake transporters or limited by efflux transporters and metabolic enzymes in the intestine. The present study aimed to characterize the Ussing chamber system incorporating human intestinal tissue as an in vitro model for investigating the impact of intestinal uptake/efflux transporters on the intestinal absorption of substrate drugs in humans. We confirmed the functions of major intestinal uptake/efflux drug transporters in freshly isolated human jejunum sections by demonstrating a significant decrease in the mucosal uptake of cefadroxil (peptide transporter 1) and methotrexate (proton-coupled folate transporter), mucosal-to-serosal permeability of ribavirin (concentrative nucleoside transporters/equilibrative nucleoside transporters), and serosal-to-mucosal permeability of P-glycoprotein and breast cancer resistance protein substrates in the presence of their typical inhibitors. The mucosal-to-serosal apparent permeability coefficients (Papp) of 19 drugs, including substrates of drug transporters and cytochrome P450 3A, ranged from 0.60 × 10-6 to 29 × 10-6 cm/s and showed a good correlation with reported fraction of an oral dose that enters the gut wall and passes into the portal circulation with escaping intestinal metabolism (FaFg) values in humans. Furthermore, the Papp values for cefadroxil, methotrexate, and ribavirin in the presence of the corresponding transporter inhibitors underestimated the FaFg of these drugs, which clearly showed that intestinal uptake transporters facilitate their intestinal absorption in humans. In conclusion, the functions of major intestinal uptake/efflux drug transporters could be maintained in freshly isolated human jejunum sections. The Ussing chamber system incorporating human intestinal tissue would be useful for evaluating the impact of intestinal uptake/efflux transporters on the intestinal absorption of various types of drugs in humans. SIGNIFICANCE STATEMENT: Although previous studies have predicted the intestinal absorption of drugs in humans using the Ussing chamber system incorporating human intestinal tissue, there is little systematic information about drug transport mediated by multiple transporters in this system. We confirmed the functions of major intestinal uptake/efflux transporters in freshly isolated human jejunum sections and demonstrated that the mucosal-to-serosal apparent permeability coefficient of various types of drugs showed a good correlation with reported human FaFg values.

An image-based geometric model for numerical simulation of blood perfusion within the liver lobules.

An image-based numerical algorithm is presented for simulating blood flow through the liver tissue. First, a geometric model is constructed by applying image processing techniques on a real microscopic image of a liver tissue. Then, incompressible blood flow through liver lobules is simulated. Effects of tissue heterogeneity and deformity, presence/absence of the second central vein in a particular lobule, and apparent sinusoids density in the liver cross section on the blood flow are investigated. Numerical results indicate that the existence of thick low permeability vascular septum, high permeability sinusoids, and lobule tissue heterogeneity can considerably affect interlobular and intralobular blood flow.

The Efficacy of Sonazoid-enhanced Ultrasonography in Decision-making for Liver Abscess Treatment.

Objective The usefulness of contrast-enhanced ultrasonography (CEUS) for making decisions in the treatment of liver abscess is unknown. Methods We evaluated the internal blood flow in the arterial-predominant phase by CEUS using Sonazoid® in 21 patients. The stain area rate was evaluated in maximum parting plane of abscess in CEUS. Patients were divided into two groups: the vascular phase enhancement (VE) group, in which ≥50% of the abscess cavity was enhanced (12 patients), and the vascular phase non-enhancement (VNE) group, in which <50% of the abscess cavity was enhanced (9 patients). The rate of patients who were cured by conservative treatment alone was examined in both groups. The defect rate of all liver abscesses in the post-vascular phase was also evaluated. Results In the VE group, improvement by conservative treatment alone was obtained in 11 out of 12 patients (91.7%), while in the VNE group, improvement by conservative treatment alone was obtained in only 1 out of 9 patients (11.1%), a significant difference (p<0.001). In the VE group, one patient did not improve with conservative treatment alone because the abscess ruptured near the liver surface. In the VE group, the abscess size was smaller than in the VNE group. By examining the defect rate in the post-vascular phase, it was found that 16 out of 21 patients (76.2%) showed 71% or more defects. Conclusion The enhancement rate in the arterial-predominant phase of CEUS was considered useful for determining the treatment approach for liver abscess.

Model Assisted Analysis of the Hepatic Arterial Buffer Response During Ex Vivo Porcine Liver Perfusion.

OBJECTIVE: The hepatic arterial buffer response is a well-known phenomenon in hepatic circulation, describing the response of hepatic arterial resistance to changes in portal vein flow. Several vasoactive metabolites underlying its mechanism have been proposed, however, there is currently no clear consensus. The aim of this study is to investigate the hepatic arterial buffer response of porcine livers preserved in a controlled ex vivo perfusion machine. METHODS: Porcine livers are perfused on an ex vivo perfusion machine and hemodynamic experiments investigating the hepatic arterial resistance response to portal vein flow and vena cava pressure variations are conducted. A simple hemodynamic model is developed to support the interpretation of the received measurements. Further, a mechanism is proposed that explains hepatic arterial resistance changes in response to vena cava pressure as myogenic and in response to portal vein flow as a combined washout and myogenic effect. RESULTS: A clear correlation between hepatic sinusoidal pressure levels and hepatic arterial resistance is observed where an increase of approximately 4 mmHg of hepatic sinusoidal pressure level results in doubling of the hepatic arterial resistance. This relation is considered during the analysis of the portal vein flow variations resulting in a reduced isolated effect of adenosine washout on hepatic arterial resistance. With an average buffer capacity of 27% during our experiments, the hepatic arterial buffer response shows to be unimpaired in the ex vivo scenario. CONCLUSION: First, washout and myogenic effects both influence the hepatic arterial buffer response; and second, hepatic sinusoidal pressure levels strongly influence the hepatic arterial resistance. SIGNIFICANCE: These results present new findings in hemodynamics of the liver, which are fundamental for successful ex vivo liver perfusion.

Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis.

Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB1 and CB2 receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.

Anatomically based simulation of hepatic perfusion in the human liver.

Liver structures of a healthy subject are digitised and segmented from computed tomography (CT) images, and hepatic perfusion is modelled in the hepatic artery and portal vein of the healthy subject with structured tree-based outflow boundary conditions. This self-similar structured tree is widely used in the literature, eg, blood flow simulation in larger systemic arteries and cerebral circulation, and is used in this study to model the effect of the smaller hepatic arteries and arterioles, as well as the smaller hepatic portal veins and portal venules. Physiologically reasonable results are obtained. Since the structured tree terminates at the size of the microvasculature system in liver lobules, the structured tree boundary condition will enable the proposed organ-level model of hepatic arterial flow to be easily connected to tissue-level models of liver lobules. Blood flow in the hepatic vein is also modelled in this subject with three-element Windkessel model as outflow boundary conditions. The benefit of integrating the perfusion in all hepatic vascular vessels is that it helps us analyse some complicated clinical phenomenon more efficiently, eg, one possible application is to obtain the portal pressure gradient (PPG) to help examine the reliability of hepatic venous pressure gradient (HVPG) as an indirect measure of portal pressure. Moreover, since four to six generations of hepatic vessels, which are sufficient for liver classification analysis, were employed in the model, this study is setting the computational foundation of a potentially handy surgical tool.

Multicollinearity and misleading statistical results.

Multicollinearity represents a high degree of linear intercorrelation between explanatory variables in a multiple regression model and leads to incorrect results of regression analyses. Diagnostic tools of multicollinearity include the variance inflation factor (VIF), condition index and condition number, and variance decomposition proportion (VDP). The multicollinearity can be expressed by the coefficient of determination (Rh2) of a multiple regression model with one explanatory variable (Xh) as the model's response variable and the others (Xi [i ≠ h]) as its explanatory variables. The variance (σh2) of the regression coefficients constituting the final regression model are proportional to the VIF. Hence, an increase in Rh2 (strong multicollinearity) increases σh2. The larger σh2 produces unreliable probability values and confidence intervals of the regression coefficients. The square root of the ratio of the maximum eigenvalue to each eigenvalue from the correlation matrix of standardized explanatory variables is referred to as the condition index. The condition number is the maximum condition index. Multicollinearity is present when the VIF is higher than 5 to 10 or the condition indices are higher than 10 to 30. However, they cannot indicate multicollinear explanatory variables. VDPs obtained from the eigenvectors can identify the multicollinear variables by showing the extent of the inflation of σh2 according to each condition index. When two or more VDPs, which correspond to a common condition index higher than 10 to 30, are higher than 0.8 to 0.9, their associated explanatory variables are multicollinear. Excluding multicollinear explanatory variables leads to statistically stable multiple regression models.

Shift in Sympathovagal Balance Toward Parasympathetic Predominance Is Associated With Attenuation of Portal Hyperperfusion in Cirrhotic Recipients Undergoing Living Donor Liver Transplant.

BACKGROUND: The autonomic innervation to a liver graft remains lost up to 1 year after liver transplant. Therefore, we investigated the effects of recipients' autonomic nervous activity on the extent of portal hyperperfusion of a partial liver graft in the absence of the autonomic innervation. METHODS: A total of 31 cirrhotic recipients undergoing right lobe living donor liver transplant were analyzed. Following a 10-minute absence of surgical stimulation after hepatic artery and bile duct reconstruction, the electrocardiogram and blood pressure waveforms were recorded for 5 minutes. Low-frequency (LF) and high-frequency (HF) powers and their ratio (LF/HF) were calculated using fast Fourier transform from the electrocardiogram waveform. A decrease in LF/HF represents a shift in sympathovagal balance toward parasympathetic predominance. Then, portal venous (PVF) and hepatic arterial (HAF) blood flows were measured in mL/min per 100 g of liver weight using spectral Doppler ultrasonography. A decrease in their ratio (PVF/HAF) represents attenuation of portal hyperperfusion. RESULTS: The medians of the PVF and HAF were 349 and 27 mL/min/100 g liver weight with interquartile ranges of 272 to 617 mL/min/100 g liver weight and 22 to 41 mL/min/100 g liver weight, respectively, yielding a median of the PVF/HAF of 13.7 (interquartile range, 8.5-21.3). The median of LF/HF was 0.67 (interquartile range, 0.16-1.45). With a reduction in LF/HF, PVF/HAF decreased according to an S-curve regression model between them (PVF/HAF=e2.743+-0.031LF/HF,adjustedR2=0.129,P=0.027). CONCLUSION: A shift in sympathovagal balance toward parasympathetic predominance is associated with attenuation of portal hyperperfusion in a partial liver graft.

Portal hyperperfusion after major liver resection and associated sinusoidal damage is a therapeutic target to protect the remnant liver.

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model (n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control (n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min-1·100 g-1 preoperatively to 240 (48) mL·min-1·100 g-1 at 6 h after resection (P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min-1·100 g-1 preoperatively to 7.7 (1.7) mL·min-1·100 g-1 8 h after resection (P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o2) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection.NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.

Comparison of Patients With and Without Anterior Sector Venous Drainage in Right Lobe Liver Transplantation From Live Donors in Terms of Complications, Rejections, and Graft Survival: Single-Center Experience.

AIM: The issue of performing an anastomosis of the anterior sector veins to the vena cava in living donor liver transplantation is still controversial. We aimed to research whether there was any difference in terms of complications, rejections, and graft survival between patients with and without anterior sector venous drainage to the vena cava. PATIENTS AND METHODS: Patients were retrospectively investigated for demographic data and ratio of graft needed to available graft weight. Donors had volumetric calculations and middle hepatic vein anterior sector drainage documented in detail. RESULTS: Seventy-three donors with middle hepatic vein drainage were included. Thirty-five had anterior sector venous drainage performed and 38 patients did not have drainage procedures performed. The incidence of general complications was higher in the group without anterior sector drainage (78.3% and P = .002). Biloma linked to bile leaks were observed in 8 patients without drainage (72.8%) and 3 patients with drainage (27.2%). Late acute rejection occurring during follow up after transplantation was identified in 28 patients (11.6%). Of these, 1 (14.3%) had anterior sector drainage and 6 (85.7%) were in the patient group without drainage (P = .067). CONCLUSION: As a result of this study, for patients with grafts at the volume limit (graft weight to receiver weight ratio <0.8) and with congestion observed in the anterior sector after liver implantation and for patients with outflow problems identified on Doppler ultrasonography, anterior sector veins >5 mm should definitely be drained into the vena cava. Hence, both complication and rejection rates will reduce, and we can lengthen the graft, and thus patient, survival.

Hepato-splanchnic circulatory stress: An important effect of hemodialysis.

The gastro-intestinal tract is being increasingly recognized as the site of key pathophysiological processes in the hemodialysis patient. Intestinal dysbiosis, increased intraluminal toxin production, and increased intestinal permeability are commonly observed processes which contribute to the pathogenesis of cardiovascular disease and thus elevated mortality. The acute circulatory effects of dialysis itself may contribute significantly to the development of gastrointestinal dysfunction as a result of both local and distant effects. Additionally, the liver, a relatively unknown entity in this process, has a substantial role as a functional barrier between the portal and systemic circulation and in the metabolism of pathogenic gut-derived uremic toxins. Here we summarize the evidence for acute gastro-intestinal and hepatic effects of hemodialysis and identify gaps in knowledge to date which require further study.

Study of Hepatic Vascular Dynamics Based on Symmetrical Pulsating Perfusion.

BACKGROUND The traditionally used perfusion method is constant flow. This study proposes a novel method called Symmetric Pulsating Flow (SPF) and verified that this method is applicable. MATERIAL AND METHODS The fluid dynamic behavior of perfusate in the vessel, the shear stress, and the vascular deformation were simulated based on the bi-directional fluid-structure interaction. The differences of the fluid dynamic behaviors and the mechanical characteristics of vascular wall were studied and compared between the 2 methods during the process of hepatic perfusion. The simulations and comparisons were carried out on 3 different vascular models. RESULTS Utilizing the constant flow perfusion, a double vortex clearly appeared at the rear end of the foreign matter and reflux retention can be caused by the double vortex. The reflux retention caused lower shear stress against the vascular wall and thus brought new accumulation of foreign matter. The SPF perfusion, however, prevented the double vortex, and avoided such reflux retention during the vascular perfusion. In addition, the SPF can clean the vascular wall better with a slower speed, which causes less injury to the vessel, and the pulsating effect can reduce the accumulation of new foreign matter. CONCLUSIONS The SPF perfusion can clean the vascular wall more thoroughly with less injury.