Hepatic Hemodynamics Research Articles

Doppler evaluation of hepatic hemodynamics after living donor liver transplantation in infants.

Objective: The aim of this study was to explore the hemodynamic changes of hepatic artery and portal vein detected by Doppler ultrasound (DU) in infants who underwent living donor liver transplantation (LDLT). Methods: The data of 41 infant patients (22 Males, 19 Females, median age of 5 months) were collected in the Children’s Hospital affiliated to the Chongqing Medical University from May 2018 to December 2019. The patients underwent left lateral segment LDLT (LLS -LDLT) because of biliary atresia (BA). Hemodynamic parameters, including the peak systolic velocity (PSV), resistivity index (RI) of the hepatic artery (HA), portal vein velocity (PVV), and portal vein flow (PVF) were recorded from Doppler ultrasound on the day before the operation, and on the 1st, the 7th, the 14th and the 30th day after LDLT procedures. The changes of PSVHA, RIHA, PVV and PVF before and on the 1st day after transplantation were analyzed by paired t-test. The comparison of the data between different postoperative time points were assessed by ANOVA. Results: Compared with the parameters measured before LDLT, PSVHA, and RIHA decreased, and PVV and PVF increased significantly (p < 0.001) on the 1st day after LLS-LDLT. As for PSV, there was no significant difference between the 7th day and the 1st day after transplantation (POD7 VS POD1, p = 0.167) while there was a substantial difference between the 14th, 30th and 1st day after LT (POD14 vs. POD1, p = 0.003) (POD30 vs. POD1, p < 0.001). And there was a significant difference between the 14th, 30th, and 7th days after LT (POD14 vs. POD7, p = 0.014) (POD30 vs. POD7, p < 0.001). There was no significant difference between 30th and 14th after transplantation (POD30 vs. POD14, p = 0.092). As for RIHA and PVV, the decrease was slow within the first month after the operation, and there was no significant difference at different times. Conclusion: We have identified major hepatic flow changes that occurred in 41 infants who underwent LLS -LDLT due to BA. The data could be used for future studies of LDLT in infants including hemodynamic modeling, liver regeneration and clinical management.

Effects of endoscopic injection sclerotherapy for esophagogastric varices on portal hemodynamics and liver function

ObjectivesTo identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function.MethodsWe selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS.ResultsLow value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence.ConclusionsPatients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS.

State of liver functional activity in children with atopic dermatitis

BACKGROUND: The problem of atopic dermatitis today remains one of the unsolved problems of pediatrics and pediatric allergology. Among the etiopathogenetic mechanisms of atopic dermatitis, the role of endo-allergens formed as a result of impaired digestion and absorption processes in the gastrointestinal tract of a child is separately noted. In such conditions, the load on the detoxification function of the liver increases. In connection with this circumstance, the study of the functional activity of the liver in children with atopic dermatitis is of particular interest. One of its criteria is the nature of intrahepatic hemodynamics.&#x0D; AIM: To find out the features of intrahepatic hemodynamics in the development of atopic dermatitis in children.&#x0D; MATERIALS AND METHODS: 83 children aged 6 months to 5 years with a diagnosis of atopic dermatitis, who made up the main research group, and 33 practically healthy children of the same age, who formed a control group, were examined. The nature of heredity for allergic pathology and morbidity of the gastrointestinal tract was found out in all patients. To obtain information about the functional activity of the liver in all children, hepatic blood flow in the hepatic artery and hepatic vein was studied.&#x0D; RESULTS: Violation of intrahepatic hemodynamics was revealed in children with atopic dermatitis. The blood flow in the hepatic artery in them was characterized by a decrease, and the blood flow in the hepatic vein was characterized by an increase in speed indicators. The detected violations of intrahepatic hemodynamics in children with atopic dermatitis are regarded by the authors of this study as a manifestation of a decrease in the functional activity of hepatocytes in conditions of increased allergenic load.&#x0D; CONCLUSIONS: The study clearly demonstrated a violation of the functional state of hepatocytes in children suffering from atopic dermatitis, expressed in the suppression of hepatic hemodynamics. The question of the primary or secondary nature of this violation is the subject of discussion and further scientific research.

Assessment of hepatic arterial hemodynamics with 4D flow MRI: in vitro analysis of motion and spatial resolution related error and in vivo feasibility study in 20 volunteers.

To assess the ability of four-dimensional (4D) flow MRI to measure hepatic arterial hemodynamics by determining the effects of spatial resolution and respiratory motion suppression in vitro and its applicability in vivo with comparison to two-dimensional (2D) phase-contrast MRI. A dynamic hepatic artery phantom and 20 consecutive volunteers were scanned. The accuracies of Cartesian 4D flow sequences with k-space reordering and navigator gating at four spatial resolutions (0.5- to 1-mm isotropic) and navigator acceptance windows (± 8 to ± 2 mm) and one 2D phase-contrast sequence (0.5-mm in -plane) were assessed in vitro at 3 T. Two sequences centered on gastroduodenal and hepatic artery branches were assessedin vivo for intra - and interobserver agreement and compared to 2D phase-contrast. In vitro, higher spatial resolution led to a greater decrease in error than narrower navigator window (30.5 to -4.67% vs -6.64 to -4.67% for flow). In vivo, hepatic and gastroduodenal arteries were more often visualized with the higher resolution sequence (90 vs 71%). Despite similar interobserver agreement (κ = 0.660 and 0.704), the higher resolution sequence had lower variability for area (CV = 20.04 vs 30.67%), flow (CV = 34.92 vs 51.99%), and average velocity (CV = 26.47 vs 44.76%). 4D flow had lower differences between inflow and outflow at the hepatic artery bifurcation (11.03 ± 5.05% and 15.69 ± 6.14%) than 2D phase-contrast (28.77 ± 21.01%). High-resolution 4D flow can assess hepatic artery anatomy and hemodynamics with improved accuracy, greater vessel visibility, better interobserver reliability, and internal consistency. • Motion-suppressed Cartesian four-dimensional (4D) flow MRI with higher spatial resolution provides more accurate measurements even when accepted respiratory motion exceeds voxel size. • 4D flow MRI with higher spatial resolution provides substantial interobserver agreement for visualization of hepatic artery branches. • Lower peak and average velocities and a trend toward better internal consistency were observed with 4D flow MRI as compared to 2D phase-contrast.

Graft Inflow Modulation in Living-Donor Liver Transplantation: Hepatic Hemodynamic Changes in Splenic Artery Ligation and Splenectomy.

BackgroundExcessive portal flow to an allograft was a key mechanism for small-for-size syndrome in living-donor liver transplantation (LDLT). Good outcomes in LDLT by graft inflow modulation (GIM) using a small graft were reported, but the effect on hepatic hemodynamics is undefined. This report summarizes our experience with GIM and compares the effects of splenic artery ligation (SAL) and splenectomy on hepatic hemodynamic changes.Material/MethodsNinety-nine patients who underwent adult-to-adult LDLT from June 2014 to December 2020 were included in this study. GIM was performed in 36 patients (17 patients with SAL and 19 with splenectomy).ResultsThe GIM group had lower graft-to-recipient weight compared to the no-modulation group (median, 0.91% versus 1.04%, P=0.022). Initial portal venous flow (PVF) was higher in the GIM group (median, 311 versus 156 ml/min/100 g, P<0.001). After GIM, PVF decreased to 224 ml/min/100 g. One-year graft survival with GIM was 89.9%, and for the no-modulation group it was 86.6% (P=0.945). In the subgroup analysis, the efficacy of decompressing PVF was higher in the splenectomy subgroup (median, 14.3% versus 41.8%, P=0.002).ConclusionsGIM was useful for grafts with high PVF. Splenectomy modulated excessive PVF more effectively than did SAL. Perioperative hepatic hemodynamic changes could assist surgeons in selecting different GIM strategies.

Hyperspectral evaluation of liver oxygenation in a murine model of metabolic associated liver disease and hepatocellular carcinoma

Abstract Objective Untreated MAFLD is a continuum of disease ranging from hepatic steatosis to cirrhosis and hepatocellular carcinoma (HCC). Throughout the disease progression, a change in hepatic hemodynamics occurs as portal hypertension. Hepatic arterial buffer response is a compensatory mechanism to maintain liver perfusion facing reduction of portal flow. These changes could also impair hepatic oxygenation homeostasis. The aim of this study is to test this hypothesis in mouse models and to shed light on the oxygenation of fatty, portal hypertensive liver and its impact on HCC carcinogenesis. Methods C57BL/6 mice were fed a HFD starting from 4 weeks of age, porto-systemic shunts (or sham) were created at 8 weeks, and monitored up to 40 weeks. ND-fed non-shunted mice were used as control group. Hyperspectral imaging (HSI) was utilized to quantify tissue oxygenation (StO2) of ND, HFD and HFD-shunted mice. In a second set of experiment, we explored the role of a common hepatic artery ligation in the studied DEN-induced HFD mouse model. Results HFD induced hepatic steatosis and portal pressure compared to ND. Porto-systemic shunt could deviate about 67% of the portal flow through the spleen to the systemic circulation, thus reducing portal pressure close-to-normal levels. Compared to control mice, HFD feeding increased liver oxygenation (p=0.0004), while shunting restored a close to normal level (p&amp;lt;0.001). The oxygenation of small bowel is decreased in a similar manner in both HFD and HFD-shunted mice. In HFD-fed mice, artery ligation led to less carcinogenesis compared to mice without artery ligation (p=0.026). In addition, artery ligation was also associated with smaller HCCs (p=0.027). Conclusion Early stages of MAFLD alter hepatic oxygen homeostasis. Fatty liver, when associated to portal hypertension, express higher liver oxygenation levels, compared to control group. This could due to hepatocyte ballooning with a narrowing of portal system, thus bring portal hypertension state with a simultaneous arterial buffer response. Additionally, small bowel of portal hypertensive mice showed lower oxygen levels mirroring an intestinal venous congestion typical of portal hypertension. Oxygen deprivation, through artery ligation, decreases HCC carcinogenesis and reduces HCC nodules volume. Yet further research is needed but oxygen homeostasis seems play a role in MAFLD progression as well in HCC pathophysiology.

Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure.

Interactions of the heart and the liver remain to be fully understood in the pathophysiology of heart failure (HF). Hepatokines are proteins synthesized and secreted from the liver and regulate systemic metabolisms of peripheral tissues. This study sought to clarify the clinical relevance of hepatokine Fetuin-A in patients with HF. We enrolled 217 participants including 187 hospitalized patients with HF and 30 control subjects who were sought with a comparable age- and sex profile and who had never had HF or structural cardiac abnormalities. First, we examined the levels of Fetuin-A and found that its levels were significantly lower in patients with HF than in the controls. Next, HF patients were categorized into four groups based on hepatic hemodynamics assessed by abdominal ultrasonography which determines liver hypoperfusion by peak systolic velocity (PSV) of the celiac artery and liver stiffness by shear wave elastography (SWE). Fetuin-A levels were significantly decreased in HF patients with liver hypoperfusion compared to those without, but were not different between HF patients with and without elevated liver stiffness. Correlation analysis revealed that circulating Fetuin-A was positively correlated with PSV of the celiac artery but not with SWE of the liver. Kaplan-Meier analysis demonstrated that HF patients with lower Fetuin-A levels were significantly associated with increased adverse outcomes including cardiac deaths and decompensated HF. Liver-derived hepatokine Fetuin-A may be a novel target involved in the cardio-hepatic interactions, as well as a useful biomarker for predicting the prognosis in patients with HF.

Hepatic Positron Emission Tomography: Applications in Metabolism, Haemodynamics and Cancer.

Evaluating in vivo the metabolic rates of the human liver has been a challenge due to its unique perfusion system. Positron emission tomography (PET) represents the current gold standard for assessing non-invasively tissue metabolic rates in vivo. Here, we review the existing literature on the assessment of hepatic metabolism, haemodynamics and cancer with PET. The tracer mainly used in metabolic studies has been [18F]2-fluoro-2-deoxy-D-glucose (18F-FDG). Its application not only enables the evaluation of hepatic glucose uptake in a variety of metabolic conditions and interventions, but based on the kinetics of 18F-FDG, endogenous glucose production can also be assessed. 14(R,S)-[18F]fluoro-6-thia-Heptadecanoic acid (18F-FTHA), 11C-Palmitate and 11C-Acetate have also been applied for the assessment of hepatic fatty acid uptake rates (18F-FTHA and 11C-Palmitate) and blood flow and oxidation (11C-Acetate). Oxygen-15 labelled water (15O-H2O) has been used for the quantification of hepatic perfusion. 18F-FDG is also the most common tracer used for hepatic cancer diagnostics, whereas 11C-Acetate has also shown some promising applications in imaging liver malignancies. The modelling approaches used to analyse PET data and also the challenges in utilizing PET in the assessment of hepatic metabolism are presented.

Features of hepatobiliary system function in biliary dyskinesia in children with type 1 diabetes mellitus

A study of intrahepatic hemodynamics was conducted in 150 children aged 11 to 14 years, of which 33 were practically healthy children, 117 were patients with biliary dyskinesia (85 with type 1 diabetes, 32 without type 1 diabetes). In patients with biliary dyskinesia, a decrease in the speed of blood flow in the hepatic artery with an increase in indices (resistance, pulsation, systolic-diastolic), as well as an increase in the speed of blood flow in the hepatic vein with a decrease in these indices was revealed. The inhibition of hepatic hemodynamics may be due to the deterioration of bile secretion, as a result of a violation of the normal innervation of the bile system, associated with the development of diabetic neuropathy in children with type 1 diabetes. It is suggested that angiopathy of hepatic arteries and veins plays a certain role in the Genesis of intrahepatic blood flow disorders.

The Impact of Injection Distance to Bifurcations on Yttrium-90 Distribution in Liver Cancer Radioembolization

PurposeTo model the effect of the injection location on the distribution of yttrium-90 (90Y) microspheres in the liver during radioembolization using computational simulation and to determine the potential effects of radial movements of the catheter tip. Materials and MethodsNumerical studies were conducted using images from a representative patient with hepatocellular carcinoma. The right hepatic artery (RHA) was segmented from contrast-enhanced cone-beam computed tomography scans. The blood flow was investigated in the trunk of the RHA using numerical simulations for 6 injection position scenarios at 2 sites located at a distance of approximately 5 and 20 mm upstream of the first bifurcation (RHA diameters of approximately 4.6 mm). The 90Y delivery to downstream vessels was calculated from the simulated hepatic artery hemodynamics. ResultsVarying the injection location along the RHA and across the vessel cross-section resulted in different simulated microsphere distributions in the downstream vascular bed. When the catheter tip was 5 mm upstream of the bifurcation, 90Y distribution in the downstream branches varied by as much as 53% with a 1.5-mm radial movement of the tip. However, the catheter radial movement had a weaker effect on the microsphere distribution when the injection plane was farther from the first bifurcation (20 mm), with a maximum delivery variation of 9% to a downstream branch. ConclusionsAn injection location far from bifurcations is recommended to minimize the effect of radial movements of the catheter tip on the microsphere distribution.

Refractory ascites of complex genesis in patients with a severe combined form of extrahepatic portal hypertension

This study demonstrates a successful clinical outcome in a female patient with severe refractory ascites associated with a complex combined form of extrahepatic portal hypertension. The study emphasizes the need and particular importance of comprehensive diagnostics and assessment of the angioarchitectonics in the portal vein system, thorough study of the porto–hepatic circulation and central hemodynamics, as well as of other major homeokinesis disorders. Understanding the pathogenesis of the disease allows for the development of a therapeutic plan with a strictly personalized approach toward the selection and staging of various surgical interventions.

Doppler profiles of renal and hepatic hemodynamics in patients with cirrhosis of the liver

One in five individuals with cirrhosis of the liver may experience renal impairment, a frequent consequence that is linked to increased mortality and morbidity. Even before changes in serum creatinine concentration can be detected, renal hemodynamic alterations start to occur early in the course of functional kidney failure caused by liver disease. Studying the Doppler profiles of renal and hepatic hemodynamics in people with liver cirrhosis is the goal of this review article. People with liver cirrhosis, even before clinical signs of renal impairment appear. Doppler is a quick, reliable, and noninvasive technique that makes it possible to identify renal hemodynamic changes in individuals with liver cirrhosis even before they become clinically obvious.

Triplex Sonographic Evaluation of Portal Vein Indices Among Adults in Port Harcourt, Nigeria.

Chronic liver disease is characterized by progressive hepatic fibrosis and changes in hepatic vascular hemodynamics. Sonography is a readily available tool in the assessment of the hepatic hemodynamic alterations that occur in chronic liver diseases. This study was aimed at sonographically determining the portal vein indices in apparently healthy adults by estimating the portal vein diameter, cross-sectional area, and portal vein velocity. This was a prospective, cross-sectional study carried out among 62 apparently healthy individuals. The participants underwent gray scale and Doppler ultrasonographic examinations of the portal vein. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) IBM Corp. version 23.0 (Armonk, NY: USA). The comparison of means of two groups was with the unpaired t-test, and level of significance was set at 5% (P < 0.05). Forty-six (74.2%) of the 62 participants recruited were male and 16 (25.8%) were female. Participants were aged 18-65 years with a mean age of 39.90 ± 10.34 years. The means of portal vein diameter, cross-sectional area, and portal vein velocity are 1.15 ± 0.12 cm, 0.88 ± 0.18 cm2, and 18.37 ± 2.04 cm/s, respectively. There was no statistically significant difference of all portal vein ultrasound parameters between males and females, except portal vein flow velocity which was higher in males, t-test = 2.273 and P = 0.027 (>0.05). There was no significant correlation between age and ultrasound parameters P > 0.05. The normal values of portal vein diameter, cross-sectional area, and portal vein velocity were established.

Systemic Inflammation and Endotoxemia in Peripheral and Hepatic Venous Circulation with its Correlation with Hepatic Venous Pressure Gradient in Patients with Acute Variceal Bleeding: A Proof of Concept

Background: Limited data exist regarding systemic inflammation and endotoxemia in different circulatory compartments in patients with acute variceal bleeding (AVB). Further, the correlation of these circulatory abnormalities with hepatic venous pressure gradient (HVPG) in AVB remain unexplored. Aim: To assess the circulatory milieu of peripheral and hepatic venous blood with regard to inflammation and endotoxemia and evaluated their correlation with HVPG in patients with AVB. Methods: In this prospective pilot study, serum interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), IgM anti-endotoxin antibody (indirect marker of endotoxemia) were evaluated simultaneously on day-2 of AVB in peripheral vein and hepatic vein at the time of HVPG estimation. Peripheral and hepatic venous circulatory milieu of different parameters was compared using scatter plots. Association of HVPG with parameters in different compartments was evaluated using spearman’s correlation. Results: Systemic circulatory cytokines, endotoxemia and HVPG were evaluated in 27 patients with AVB [mean age: 45.3±13 years, 66% males, mean MELD score: 15±4] with concomitant evaluation of hepatic venous components in a subset (n=16). On comparing hepatic and peripheral venous milieu, while IL-6 (r=0.53, P=0.034) and TNFα (r=0.55, P=0.03) correlated with each other in these compartments, endotoxemia (r=0.074, P=0.79), IL-1 (r=0.19, P=0.49) and CRP (R=0.18, P=0.51) did not. Peripheral venous IL-6 (r=0.71, P=0.001) correlated with HVPG whereas IL-1 (r=0.18, P=0.38), TNFα (r=0.33, P=0.097), CRP (R=0.021, P=0.92) and endotoxemia (r= -0.32, P=0.11) did not. None of the parameters in hepatic venous samples showed correlation with HVPG. Conclusions: The present study provides a proof-of concept of compartment specific pattern of systemic inflammation and endotoxemia in AVB. The association of peripheral but not hepatic venous IL-6 with HVPG suggests the role of systemic response to the event (AVB) as the source of inflammation and possibly a determinant of hepatic hemodynamics in AVB. Endotoxemia (both peripheral and hepatic venous) has a limited role in determining the hepatic hemodynamics in AVB.

A postresection perfusion deficit in the right colon is an independent predictor of perioperative outcome after major hepatectomy

There is a strong interaction between hepatic hemodynamics and perfusion in the splanchnic system. However, little is known about differences in perfusion in different splanchnic compartments and their changes after hepatectomy. Perfusion in various splanchnic compartments (ie, stomach, small intestine, right and left colon, liver) was assessed pre- and post-hepatectomy by intraoperative laser Doppler flowmetry. Differences of splanchnic perfusion between compartments were evaluated by ANOVA, and risk factors of postoperative complications (graded by the comprehensive complication index [CCI]) were analyzed by univariate and multivariate analyses. A prediction model of postoperative complications was developed. A total of 50 and 29 patients with major and minor hepatectomy were enrolled. Splanchnic perfusion at baseline varied significantly across different splanchnic compartments with highest values in the small bowel and right colon (P<.001). Major hepatectomy induced a significant perfusion decrease in the stomach (P=.006), right colon (P<.001) and small bowel (P=.035). A postresection perfusion deficit in the right colon with values below 254 perfusion units (PU) was identified as an independent predictor of clinically relevant complications after major hepatectomy (concordance index: 0.79, 95% CI 0.66-0.87, P=.002). Bootstrap validation confirmed internal validity and excellent calibration. Major hepatectomy causes significant reduction of splanchnic perfusion. An intraoperative posthepatectomy microcirculatory perfusion deficit of the right colon is a strong and independent predictor of clinically relevant postoperative complications after major hepatectomy.

Influence of cytokines, circulating markers and growth factors on liver regeneration and post-hepatectomy liver failure: a systematic review and meta-analysis

The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis. Current investigations of post-hepatectomy liver failure and regeneration are focused on evaluation of circulating hepatic function parameters (transaminases, cholestasis, and coagulation parameters), volumetry and hepatic hemodynamics. However, identification of biochemical factors associated with regeneration and post hepatectomy liver failure is crucial for understanding the pathophysiology and identification of patients at risk. The objective of the present systematic review was to identify circulating factors associated with liver regeneration and post hepatectomy liver failure in patients undergoing hepatectomy. The quantitative analysis was intended if studies provided sufficient data. Electronic databases (MEDLINE via PubMed, Web of Knowledge, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on cell signaling factors in liver regeneration and post-hepatectomy liver failure following liver resection in clinical setting. No date restriction was given. No language restriction was used. Studies were assessed using MINORS. This study was registered at PROSPERO (CRD42020165384) prior to data extraction. In total 1953 publications were evaluated for titles and abstracts after exclusion of duplicates. Full texts of 167 studies were further evaluated for inclusion. 26 articles were included in the review and 6 publications were included in the meta-analyses. High levels of serum hyaluronic acid even preoperatively are associated with PHLF but especially increased levels early after resection are predictive of PHLF with high sensitivity and specificity. Postoperative elevation of HA to levels between 100 and 500 ng/ml is increased the risk for PHLF ([OR] = 246.28, 95% [CI]: 11.82 to 5131.83; p = 0.0004) Inteleukin-6 levels show contradicting result in association with organ dysfunction. HGF positively correlates with liver regeneration. Overall, due to heterogeneity, scarcity, observational study design and largely retrospective analysis, the certainty of evidence, assessed with GRADE, is very low. High levels of serum hyaluronic acid show a strong association with PHLF and increased levels after resection are predictive of PHLF with high sensitivity and specificity, even on POD1. Interleukin-6 levels need to be studied further due to contradictive results in association with organ dysfunction. For HGF, no quantitative analysis could be made. Yet, most studies find positive correlation between high HGF levels and regeneration. Prospective studies investigating HGF and other growth factors, hyaluronic acid and interleukins 1 and 6 in correlation with liver regeneration measured sequentially through e.g. volumetry, and liver function parameters, preferably expanding the analysis to include dynamic liver function tests, are needed to sufficiently illustrate the connection between biomolecule levels and clinical outcomes.

THE PECULIARITIES OF THE DATA OF INSTRUMENTAL EXAMINATIONS OF WOMEN AFFECTED BY UTERINE FIBROIDS WITH CONCOMITANT HEPATOBILIARY DISEASES

Nowadays, women’s reproductive health is a topical issue of obstetrics and gynecology, therefore, great importance is attributed to timely diagnosis and prevention of diseases that influence fertility. The topicality of the issue of uterine hyperplasia, in particular, uterine fibroids, is accounted for by the social significance of the disease. Its incidence rate is constantly growing and makes up from 30 to 50% in women older than 35 years and, according to the data of autopsy, - up to 80%. No doubt, the peculiarities of development and progression of hyperplasia are determined by the reserve potential of various systems and organs, including the hepatobiliary system.The aim of research is to analyze the results of instrumental examinations of the functional capacity of hepatocytes in women affected by uterine fibroids and functional disorders of the hepatobiliary system. Research materials and methods. To accomplish the set objective, we used the following contemporary instrumental examination methods: ultrasonography and rheovasohepatography as well as a clinical and paraclinical analysis of caserecords of 150 women aged between 35 and 45 and affected by uterine fibroids, who were treated at the gynecological department of the Regional Perinatal Centre.Research results. As the research result show, uterine fibroids and the related hormonal disorders often go together with functional and morphological lesion of hepatocytes. Patients affected by uterine fibroids have preconditions for the development of functional disorders of hepatocytes as they present significant disorders of hepatic hemodynamics, decreased blood supply of the liver, as a result of pre- and postcapillary resistance.Conclusions. There is a close connection between uterine fibroids with concomitant hepatobiliary disorders and the severity of hormonal disorders, and the significant lesion of hepatocytes may be irreversible. Thisrequires pathogenetic correction by introducing drugs with hepatoprotective and antioxidant effects.

Structural and functional changes of abdominal organs in patients with hepatocerebral degeneration

The paper presents the results of ultrasound diagnostic of 76 patients with neurological forms of hepatocerebral degeneration (HCD) or Wilson’s disease (WD), who were examined and treated at the clinic of the Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine. According to ultrasound diagnostic, all patients had pathological changes in the liver. In 58% of patients these changes corresponded to chronic hepatitis, in 42% - liver cirrhosis, and in 32% of patients were reported for portal hypertension. Background hepatic hemodynamics of patients was within normal limits, but in 82% of them the reaction to food load was negative. Doppler study showed that background hepatic hemodynamics in patients with neurological forms of hepatocerebral degeneration (GCD) was within normal limits. However, the food load showed that 82% of patients had impaired reciprocal autoregulation of liver microcirculation. This indicates a decrease in their compensatory-adaptive capacity of the liver. This position is confirmed by the fact that 70% of these patients have a decrease in vasoactive endothelial function. Our study of the functional state of the vascular endothelium showed that patients with GCD have a significant decrease in vasoactive endothelial function. In general, the group was only 8.12% at a rate of 10% or more. Despite the young average age of our patients (29.7 years), only 30% of patients had a normal vasoactive reaction. These were patients under the age of 25 from the group of chronic hepatitis. The degree of endothelial dysfunction was significantly higher in patients with liver cirrhosis compared with chronic hepatitis. According to ultrasound elastography, in the vast majority of examined patients with GCD (88%) there was increased stiffness of the liver parenchyma. On the average on group of patients it made 10,62 KPA with a range from 4,74 to 20,69 KPA (norm 0,4-6,0 KPA). Thus, patients with neurological forms of GCD, which are observed by a neurologist, it is necessary before each course of treatment, but at least 1-2 times a year, to conduct ultrasound of the abdominal cavity.

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification.

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray's Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.

Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease

In advanced chronic liver disease (ACLD), deregulated hepatic necroinflammatory processes play a key role in the development of liver microvascular dysfunction, fibrogenesis, and increased hepatic vascular tone, resulting in progression of ACLD and portal hypertension. Given the current lack of an effective treatment, we aimed to characterise the effects of the pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor in 2 preclinical models of ACLD, as well as in liver cells from patients with ACLD. Cirrhotic rats (thioacetamide or common bile duct ligation; TAA or cBDL) randomly received lanifibranor (100 mg/kg/day, po) or vehicle for 14 days (n= 12/group). PPAR expression, systemic and hepatic haemodynamics, presence of ascites, liver sinusoidal endothelial cell (LSEC) phenotype, hepatic stellate cell (HSC) activation, serum transaminases and albumin, hepatic macrophage infiltration, cytokine expression, and liver fibrosis were determined. Hepatic cells were isolated from the livers of patients with cirrhosis and their phenotype was evaluated after treatment with either lanifibranor or vehicle. TAA-cirrhotic rats receiving lanifibranor showed significantly lower portal pressure compared with vehicle-treated animals (-15%; p = 0.003) without decreasing portal blood flow, indicating improved hepatic vascular resistance. Moreover, lanifibranor-treated TAA-rats showed decreased ascites, improved LSEC and HSC phenotypes, ameliorated hepatic microvascular function, reduced hepatic inflammation, and significant fibrosis regression (-32%; p = 0.020). These findings were confirmed in the cBDL rat model as well as in human liver cells from patients with cirrhosis, which exhibited phenotypic improvement upon treatment with lanifibranor. Lanifibranor ameliorates fibrosis and portal hypertension in preclinical models of decompensated cirrhosis. Promising results in human hepatic cells further support its clinical evaluation for the treatment of ACLD. Advanced chronic liver disease (ACLD) constitutes a serious public health issue for which safe and effective treatments are lacking. This study shows that lanifibranor improves portal hypertension and liver fibrosis, 2 key elements of the pathophysiology of ACLD, in preclinical models of the disease. Evaluation of lanifibranor in liver cells from patients with ACLD further supports its beneficial effects.