Hepatic Arterial Blood Flow Research Articles

Sex‐dependent Liver Volume Recovery and Hemodynamics Measured by Non‐Invasive Ultrasound Imaging after Partial Hepatectomy in Rats

Initiation of liver regrowth after partial hepatectomy (PHx) is often linked to increased flow per unit tissue through the hepatic portal vein. Previous studies of liver hemodynamics have used surgical implants, however ultrasound‐based methods can non‐invasively measure blood flow, organ volume, and other physiological parameters.Male and female Sprague‐Dawley rats were pair‐fed liquid diet containing ethanol or carbohydrate per Lieber DeCarli protocol for 5–6 weeks prior to a 70% PHx in which left lateral and medial lobes were surgically removed. A VEVO 2100 (VisualSonics, Toronto, Canada) high‐frequency ultrasound system with a motorized‐step ultrasound transducer was utilized to calculate liver volume using a 3D mapping software. Shear‐wave elastography measured liver stiffness with an Aplio i800 ultrasound system (Canon Medical Systems, Tustin, CA, USA). Color and Spectral Doppler evaluated blood flow velocity in the portal vein (PV) and the main hepatic artery (HA) at their entry into the right lobe. Laser coupled photoacoustic imaging aided in quantification of oxygen saturation in the liver tissue.Liver regrowth as measured by liver volume was impaired in ethanol‐fed male rats as early as 48 hours after PHx, only recovering ~70% of initial volume by one week. In contrast, all other animals, including ethanol‐fed females, had recovered to ~100% of liver volume by one week post‐PHx. All animals showed increased PV and HA blood flow per liver volume immediately after PHx. Relative PV flow continued to increase by the 12‐hour time point, while relative HA flow had variable changes. Ethanol‐fed males had decreased ratio of PV/HA flow compared to all other animals prior to PHx. In the first 24 hours after PHx, relative HA flow decreased or remained stable for most groups, but increased for ethanol‐fed females. Liver stiffness increased immediately after PHx and again by 10 hours after PHx for all groups, though never reaching values that would suggest fibrosis. Stiffness remained elevated for at least 96 hours for all groups, and resolved by one week post‐PHx. Photoacoustic imaging showed liver tissue oxygen saturation fluctuating between 50–60% for all animals, with no discernable patterns.Ethanol‐fed male rats had an impaired liver volume recovery response after PHx, however this ethanol‐mediated impairment was not seen in females. Interestingly, ethanol‐fed males were the only group to have a decreased PV/HA flow ratio prior to PHx, while ethanol‐fed females were unique in their prolonged increase in HA flow at 10 hours post‐PHx. Taken together, these results implicate increased HA flow as a compensatory mechanism in chronic ethanol‐fed rats.Support or Funding InformationSupported by NIH NIAAA R01 AA018873, T32 AA007463 and NIBIB U01 EB023224.

Effects of Trendelenburg position and increased airway pressure on hepatic regional blood flow of normal and resected liver.

High portal venous blood flow (Qpv) may contribute to posthepatectomy liver failure. Both Trendelenburg position (TP) and elevated airway pressure (Paw) increase backpressure to venous return and may thereby reduce Qpv. The aim of this study was to evaluate the effects of TP and increased Paw on hepatosplanchnic hemodynamics before and after major liver resection. Arterial and venous blood pressures, Qpv, extrasplanchnic inferior vena cava (Qivc), superior mesenteric (Qsma), hepatic (Qha), and carotid artery blood flows (Qca) were measured in 14 anesthetized and mechanically ventilated pigs in supine and 30° TP during end-expiratory hold at 5 cmH2O positive end-expiratory pressure (PEEP) and during inspiratory hold with Paw of 15, 20, 25, and 30 cmH2O. After major liver resection, the interventions were repeated in seven randomly selected animals. At baseline, TP increased right atrial pressure (Pra) and Qpv but not Qivc or Qsma. With increased Paw in the supine position, Pra increased and all regional blood flows decreased. TP during increasing Paw attenuated the decrease in Qpv, Qsma, and Qivc but not in Qha or Qca. After liver resection, the effects of TP during increasing Paw remained, albeit at higher portal vein pressures. However, TP alone did not increase IVC venous return. Increasing Paw in supine position reduces Qpv and all other regional flows, while the reduction in Qpv is attenuated in TP, suggesting partly preserved liver waterfall or decreased intrahepatic resistance. Liver resection, despite resulting in major intrahepatic blood flow changes, does not fundamentally influence the interaction of increasing Paw and TP on regional perfusion.NEW & NOTEWORTHY In Trendelenburg position (TP), liver blood flow is the only contributor to increased venous return measured in the inferior vena cava (IVC), which attenuates the decreased IVC venous return induced by increasing airway pressure. After liver resection, TP similarly attenuated effects of increasing airway pressure.

Intraoperative evaluation of hepatic artery blood flow during pancreatoduodenectomy (HEPARFLOW): Protocol of an exploratory study

IntroductionPancreatoduodenectomy is the treatment of choice for a range of benign and malignant diseases. The pancreatic head must be separated from its supplying vessels, especially the gastroduodenal artery, during this operation. However, dissection of the gastroduodenal artery can disturb blood supply to the liver and result in liver ischemia. There is currently no well-established algorithm to evaluate and ensure sufficient blood flow in patients with altered hepatic artery blood flow. To address this important issue, this study aims to establish a basis for assessing liver blood supply during pancreatoduodenectomy. Furthermore, factors influencing arterial blood flow and related postoperative complications will be evaluated. Methods and analysisThe HEPARFLOW study is a single institutional single-arm prospective exploratory observational clinical trial. All consecutive patients undergoing elective partial or total pancreatoduodenectomy will be screened for inclusion until 100 patients are enrolled. Blood flow in the proper hepatic artery, gastroduodenal artery, portal vein, and additional vessels supplying the liver will be measured during pancreatoduodenectomy using Doppler flowmetry. All patients will be followed up for 90 days after surgery. At each visit, standard clinical data, postoperative complications and mortality will be recorded. DiscussionThis will be the first study to prospectively assess intraoperative flow rates of the hepatic artery and portal vein to evaluate liver blood supply during pancreatoduodenectomy. The preoperative and intraoperative factors influencing blood flow in the hepatic arteries will be identified. This study may also reveal the hemodynamic and clinical relevance of a compression of the celiac axis during pancreatoduodenectomy. Ethics and disseminationThis study was approved by the Ethics Committee of the University of Heidelberg (S-073/2018). The results will be published in a peer-reviewed journal and will be presented at medical meetings.

Improved Visualization of the Necrotic Zone after Microwave Ablation Using Computed Tomography Volume Perfusion in an In Vivo Porcine Model

After hepatic microwave ablation, the differentiation between fully necrotic and persistent vital tissue through contrast enhanced CT remains a clinical challenge. Therefore, there is a need to evaluate new imaging modalities, such as CT perfusion (CTP) to improve the visualization of coagulation necrosis. MWA and CTP were prospectively performed in five healthy pigs. After the procedure, the pigs were euthanized, and the livers explanted. Orthogonal histological slices of the ablations were stained with a vital stain, digitalized and the necrotic core was segmented. CTP maps were calculated using a dual-input deconvolution algorithm. The segmented necrotic zones were overlaid on the DICOM images to calculate the accuracy of depiction by CECT/CTP compared to the histological reference standard. A receiver operating characteristic analysis was performed to determine the agreement/true positive rate and disagreement/false discovery rate between CECT/CTP and histology. Standard CECT showed a true positive rate of 81% and a false discovery rate of 52% for display of the coagulation necrosis. Using CTP, delineation of the coagulation necrosis could be improved significantly through the display of hepatic blood volume and hepatic arterial blood flow (p < 0.001). The ratios of true positive rate/false discovery rate were 89%/25% and 90%/50% respectively. Other parameter maps showed an inferior performance compared to CECT.

Hepatic flow is an intraoperative predictor of early allograft dysfunction in whole-graft deceased donor liver transplantation: An observational cohort study.

BACKGROUNDEarly allograft dysfunction (EAD) after liver transplantation (LT) is an important cause of morbidity and mortality. To ensure adequate graft function, a critical hepatocellular mass is required in addition to an appropriate blood supply. We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.AIMTo study whether hepatic flow is an independent predictor of EAD following LT.METHODSThis is an observational cohort study in a single institution. Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow. EAD was defined using the Olthoff criteria. Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD. Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models.RESULTSA total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients. A total of 54 (27.7%) patients developed EAD. The median follow-up was 39 mo. Portal venous flow, hepatic arterial flow (HAF) and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses. HAF is an independent prognostic factor for 30-d patient mortality.CONCLUSIONIntraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD; Moreover, HAF should be considered a predictor of 30-d patient mortality.

Сlinical case of pancreatic cancer

Description of a rare case of pancreas body tumor, which was grown into celiac trunk, is presented. The patient was saved due toanftomy of right hepatic artery, which was a branch of superior mesenteric artery.&#x0D; Patient Z.V, 60 years old, came to the clinic with such complaints as pain, heaviness in abdomen and waist area,weakness.4–5 cm tumor of pancreas body was detectedduring surgery. The tumor had grown into celiac trunk and into left adrenal gland.&#x0D; The friable tissue of hepato-duodenal ligament was dissected duringthe surgery.Thesurgeons mobilized duodenum usingKoxertechnique. As a result of this manipulation, the followingblood vesselswere visualized:inferior vena cava and abdominal aorta, celiac trunk, superior mesentericartery. Surgical team opened ligament of Treitz and excisedpancreas body2.5 cm away from thetumor proximally. The stump was sewed with “mattress stich”, celiac trunk was sectioned and entangled, surgeons also dissected common hepatic artery. After section they checked blood supply of liver. The pressure of blood flowing from gastro-duodenal and pancreato-duodenal artery was enough for providing normal blood flow in the left hepatic artery.&#x0D; Morphological result of the excisedtissue — Ductal adenocarcinoma (No 672).&#x0D; The patient’sstate was satisfactory when he left the clinic. He underwent medical check-up three times next year. He feels well, his state of health is normal. Patient is capable of working.&#x0D; This case is interesting due to the anatomy of right hepatic artery (which was a branch of superior mesenteric artery) that saved patient’s life.

Predictive Value of Intraoperative Indocyanine Green Clearance Measurement on Postoperative Liver Function After Anatomic Major Liver Resection

BackgroundThe aim of this study was to evaluate the predictive value of measuring indocyanine green (ICG) clearance during intraoperative partial occlusion of liver lobes to be resected on postoperative liver function following major anatomic liver resection. MethodsWe prospectively included 46 patients, and 35 patients ultimately underwent anatomic major liver resection. ICG clearance was measured preoperatively and intraoperatively. Intraoperative ICG clearance was measured immediately after selective occlusion of hepatic arterial, portal, and hepatic venous blood flow to the liver lobes to be resected. The albumin-bilirubin (ALBI) grade, albumin-indocyanine green evaluation (ALICE) grade, platelet count, remnant liver volume per kilogram of weight (RLV/kg), and future liver remnant plasma clearance rate of ICG (ICGK-FLR) were measured preoperatively. ResultsAn intraoperative ICG retention at 15 min (I-R15) greater than 13.8% indicates transient posthepatectomy liver failure (PHLF) and Clavien-Dindo > grade I complications. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) for predicting PHLF and Clavien-Dindo > grade I complications was 0.797 and 0.734, respectively (p = 0.001 and 0.014). Furthermore, an I-R15 greater than 22.7% indicates mid-term PHLF, and the AUC was 0.911 (p < 0.0001). The I-R15 is a better predictor of PHLF than the ALBI grade, ALICE grade, platelet count, RLV/kg, and ICGK-FLR. ConclusionsIntraoperative ICG clearance measurements during partial occlusion of blood flow accurately predict postoperative liver function and could be new criteria for determining the feasibility and safety of anatomic major liver resection.

Quantitative 4D-Digital Subtraction Angiography to Assess Changes in Hepatic Arterial Flow during Transarterial Embolization: A Feasibility Study in a Swine Model

PurposeTo determine the feasibility of using time-resolved 3D-digital subtraction angiography (4D-DSA) for quantifying changes in hepatic arterial blood flow and velocity during transarterial embolization. Materials and MethodsHepatic arteriography and selective transarterial embolization were performed in 4 female domestic swine (mean weight, 54 kg) using 100–300-μm microspheres. Conventional 2D and 4D-DSA were performed before, during, and after each embolization. From the 4D-DSA reconstructions, blood flow and velocity values were calculated for hepatic arterial branches using a pulsatility-based algorithm. 4D-DSA velocity values were compared to those measured using an intravascular Doppler wire with a linear regression analysis. Paired t-tests were used to compare data before and after embolization. ResultsThere was a weak-to-moderate but statistically significant correlation of flow velocities measured with 4D-DSA and the Doppler wire (r = 0.35, n = 39, P = .012). For vessels with high pulsatility, the correlation was higher (r = 0.64, n = 11, P = .034), and the relationship between 4D-DSA and the Doppler wire fit a linear model with a positive bias toward the Doppler wire (failed to reject at 95% confidence level, P = .208). 4D-DSA performed after partial embolization showed a reduction in velocity in the embolized hepatic arteries compared to pre-embolization (mean, 3.96 ± 0.74 vs 11.8 2± 2.15 cm/s, P = .006). ConclusionQuantitative 4D-DSA can depict changes in hepatic arterial blood velocity during transarterial embolization in a swine model. Further work is needed to optimize 4D-DSA acquisitions and to investigate its applicability in humans.

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

BackgroundThe 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. MethodsA 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. ResultsThe 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). ConclusionA shift in sympathovagal balance toward parasympathetic predominance is associated with attenuation of portal hyperperfusion in a partial liver graft.

Hepatic Artery Pseudoaneurysm Rupture with Acute Portal Vein Occlusion Treated with Coronary Stent Graft and Trans-splenic Portal Vein Stenting

AbstractDelayed massive hemorrhage following pancreaticoduodenectomy is a potentially fatal condition. These patients are often not surgical candidates, and endovascular therapy is the primary option of treatment, usually trans-arterial embolization. However, the bleeding vessel can occasionally be treated with a stent graft rather than embolization. This decreases the risk of hepatic necrosis by preserving hepatic arterial blood flow, particularly in patients with compromised portal veins. The authors present a brief case report of delayed pseudoaneurysm rupture from a replaced proper hepatic artery after pancreaticoduodenectomy with resultant portal vein occlusion, caused by hematoma mass effect. The hepatic artery was treated with a coronary stent. During the same session, trans-splenic portal vein stenting was done.

Comprehensive Characterization of a Porcine Model of The “Small-for-Flow” Syndrome

IntroductionThe term “Small-for-Flow” reflects the pathogenetic relevance of hepatic hemodynamics for the “Small-For-Size” syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the “Small-for-Flow” syndrome. MethodsWe performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment. ResultsAll hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2–11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h. ConclusionThe present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the “Small-for-Flow” syndrome.

Effect of Hypotensive Brain Death on the Donor Liver and Its Mechanism in an Improved Bama Miniature Pig (Sus scrofa domestica) Model

BackgroundWe aimed to observe the effect of hypotensive brain death on the donor liver and understand its pathophysiological mechanism in improved pig model. MethodsThe model was induced using the modified intracranial water sac inflation method in 16 Bama miniature pigs. Effects of hypotensive brain death on liver function and tissue morphology were evaluated via changes in liver function enzyme index, liver tissue alkaline phosphatase levels, hourly bile flow, and liver tissue pathology. Its pathophysiological mechanism was examined on the basis of changes in portal vein blood flow, hepatic artery blood flow, portal venous endotoxin level, and liver tissue cytokine levels. ResultsAfter model establishment, portal vein blood flow, hepatic arterial blood flow, hourly bile flow, and alkaline phosphatase content in hepatic tissue significantly decreased, and serum aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase levels significantly increased. Hematoxylin-eosin staining of liver tissue showed that after model establishment, hepatic tissue injury was gradually aggravated and hepatic cells were irreversibly damaged at 7 hours. Portal vein endotoxin levels significantly increased after brain death. Tumor necrosis factor α, interleukin 1, and endothelin 1 levels in liver tissues significantly increased at 3, 6, and 12 hours after brain death (P < .05), and hypoxia-inducible factor 1–α and nitric oxide levels significantly decreased (P < .05). ConclusionsHepatic injury was progressively aggravated under hypotensive brain death. The mechanism of donor liver injury under hypotensive brain death may involve low liver perfusion, release of intestinal endotoxin and inflammatory factors (eg, tumor necrosis factor α and interleukin 1), decreased hypoxia-inducible factor 1–α, and endothelin 1 and nitric oxide imbalance.

Comparison of different 4D CT-Perfusion algorithms to visualize lesions after microwave ablation in an in vivo porcine model

Background: Accurate lesion visualization after microwave ablation (MWA) remains a challenge. Computed tomography perfusion (CTP) has been proposed to improve visualization, but it was shown that different perfusion-models delivered different results on the same data set.Purpose: Comparison of different perfusion algorithms and identification of the algorithm enables for the best imaging of lesion after hepatic MWA.Materials and methods: 10 MWA with consecutive CTP were performed in healthy pigs. Parameter-maps were generated using a single-input-dual-compartment-model with Patlak’s algorithm (PM), a dual-input-maximum-slope-model (DIMS), a dual-input-one-compartment-model (DIOC), a single-(SIDC) and dual-input-deconvolution-model (DIDC). Parameter-maps for hepatic arterial (AF) and portal venous blood flow (PF), mean transit time, hepatic blood volume (HBV) and capillary permeability were compared regarding the values of the normal liver tissue (NLT), lesion, contrast- and signal-to-noise ratios (SNR, CNR) and inter- and intrarater-reliability using the intraclass correlation coefficient, Bland-Altman plots and linear regression.Results: Perfusion values differed between algorithms with especially large fluctuations for the DIOC. A reliable differentiation of lesion margin appears feasible with parameter-maps of PF and HBV for most algorithms, except for the DIOC due to large fluctuations in PF. All algorithms allowed for a demarcation of the central necrotic zone based on hepatic AF and HBV. The DIDC showed the highest CNR and the best inter- and intrarater reliability.Conclusion: The DIDC appears to be the most feasible model to visualize margins and necrosis zones after microwave ablation, but due to high computational demand, a single input deconvolution algorithm might be preferable in clinical practice.

Contrast-enhanced ultrasonography is a feasible technique for quantifying hepatic microvascular perfusion in dogs with extrahepatic congenital portosystemic shunts.

Extrahepatic-congenital portosystemic shunt is a vascular anomaly that connects the portal vein to the systemic circulation and leads to a change in hepatic microvascular perfusion. However, an assessment of hepatic microvascular perfusion is limited by conventional diagnostic modalities. The aim of this prospective, exploratory study was to assess hepatic microvascular perfusion in dogs with extrahepatic-congenital portosystemic shunt using contrast-enhanced ultrasonography (CEUS) using perfluorobutane (Sonazoid® ). A total of 17 dogs were included, eight healthy dogs and nine with extrahepatic-congenital portosystemic shunt. The time-to-peak (TTP), rising time (RT), and rising rate (RR) in the hepatic artery, portal vein, and hepatic parenchyma, as well as the portal vein-to-hepatic parenchyma transit time (ΔHP-PV) measured from time-intensity curve on CEUS were compared between healthy and extrahepatic-congenital portosystemic shunt dogs. The RT of the hepatic artery in extrahepatic-congenital portosystemic shunt dogs was significantly earlier than in healthy dogs (P=0.0153). The TTP and RT of the hepatic parenchyma were significantly earlier in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P=0.0018 and P=0.0024, respectively). ΔHP-PV was significantly shorter in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P=0.0018). CEUS effectively revealed changes in hepatic microvascular perfusion including hepatic artery, portal vein, and hepatic parenchyma simultaneously in extrahepatic-congenital portosystemic shunt dogs. Rapid hepatic artery and hepatic parenchyma enhancements may reflect a compensatory increase in hepatic artery blood flow (arterialization) caused by a decrease in portal vein blood flow and may be used as an additional diagnostic test to distinguish extrahepatic-congenital portosystemic shunt dogs from healthy dogs.

Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia.

Noninvasive assessment of dynamic changes in liver blood flow, perfusion, and oxygenation using MRI may allow detection of subtle hemodynamic alterations in cirrhosis. To assess the feasibility of measuring dynamic liver blood flow, perfusion, and T2 * alterations in response to meal, hypercapnia, and hyperoxia challenges. Prospective. Ten healthy volunteers (HV) and 10 patients with compensated cirrhosis (CC). 3T; phase contrast, arterial spin labeling, and mapping. Dynamic changes in portal vein and hepatic artery blood flow (using phase contrast MRI), liver perfusion (using arterial spin labeling), and blood oxygenation ( mapping) following a meal challenge (660 kcal), hyperoxia (target PET O2 of 500 mmHg), and hypercapnia (target increase PET CO2 of ∼6 mmHg). Tests between baseline and each challenge were performed using a paired two-tailed t-test (parametric) or Wilcoxon-signed-ranks test (nonparametric). Repeatability and reproducibility were determined by the coefficient of variation (CoV). Portal vein velocity increased following the meal (70 ± 9%, P < 0.001) and hypercapnic (7 (5-11)%, P = 0.029) challenge, while hepatic artery flow decreased (-30 ± 18%, P = 0.005) following the meal challenge in HV. In CC patients, portal vein velocity increased (37 ± 13%, P = 0.012) without the decrease in hepatic artery flow following the meal. In both groups, the meal increased liver perfusion (HV: 82 ± 50%, P < 0.0001; CC: 27 (16-42)%, P = 0.011) with faster arrival time of blood (HV: -54 (-56-30)%, P = 0.074; CC: -42 ± 32%, P = 0.005). In HVs, increased after the meal and in response to hyperoxia, with a decrease in hypercapnia (6 ± 8% P = 0.052; 3 ± 5%, P = 0.075; -5 ± 6%, P = 0.073, respectively), but no change in CC patients. Baseline between-session CoV <15% for blood flow and <10% for measures. Dynamic changes in liver perfusion, blood flow, and oxygenation following a meal, hyperoxic, and hypercapnic challenges can be measured using noninvasive MRI and potentially be used to stratify patients with cirrhosis. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1577-1586.

Computed tomographic perfusion with 160-mm coverage: comparative analysis of hepatocellular carcinoma treated by two transarterial chemoembolization courses relative to magnetic resonance imaging findings

The aim of this study was to assess hepatocellular carcinoma (HCC) response with CT perfusion parameters before and after two transarterial chemo embolization (TACE) courses compared with MRI, and to search for predictive factors of response. 37 lesions (19 patients) were included between October 2015 and September 2017, based on the Barcelona Clinic Liver Cancer guidelines. CT perfusion with 160-mm coverage and MRI were performed before and after the first TACE course, and after the second TACE course. Quantitative perfusion parameters were compared to the response assessed with MRI using mRECIST criteria, defining response groups: complete response (CR), partial response (PR), no response (NR), response (including CR and PR), no complete response (NCR, including PR and NR). Pre-TACE blood flow (BF) and hepatic arterial blood flow (HABF) were significantly higher in lesions with post-TACE 1 CR than in those with NCR (BF: 118.8 vs. 76.3mL/100g/min, p = 0.0231; HABF: 76 vs. 44.2mL/100g/min, p = 0.0112). Pre-TACE time to peak (TTP) and mean transit time (MTT) were significantly lower in lesions with post-TACE 2 response than in those with NR (TTP: 31.5 vs. 46.1s, p = 0.0313; MTT: 15.8 vs. 22.8s, p = 0.0204). Post-TACE 1 and post-TACE 2 perfusion parameters did not exhibit any statistically significant differences relative to MRI response. Our study did not find, after a first TACE course, perfusion parameters associated with a response to a second TACE course. However, baseline perfusion parameters analysis could lead to better therapeutic management of HCC by targeting lesions likely to respond well to TACE courses.

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis.

The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

Features of diagnostics of the hepatobiliary system diffuse lesions in children with herpes viral infection caused by Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection)

Purpose: to improve the treatment quality and prognosis of herpesvirus infection in children caused by the Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection) based on the study of clinical, biochemical and immunological parameters of the hepatobiliary system. Materials and methods: We examined 95 children aged 3 to 7 years with herpesvirus infection, who were divided into three groups (the I group – children with acute Epstein-Barr infection, the II group – children with Epstein-Barr infection in combination with cytomegalovirus infection, the ІІІ group – children with Epstein-Barr infection and herpesvirus infection type 6). Age-matched healthy control group consisted of 20 children. The diagnosis was verified using a polymerase chain reaction. Biochemical studies included determination of total protein and its fractions, total bilirubin and its fractions, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, thymol index. All patients underwent echosonography of the liver. The level of cytokines (IL-1β, IL-4) and antiviral protection parameters – the content of natural killers (CD16+), T-helper (CD4 +) and/or cytotoxic lymphocytes (CD8 +) were evaluated. Results. In all examined children the disease started acutely from general intoxication syndrome, lesion of the nasopharynx and oropharynx, which were more pronounced in the children of the 1st and 2nd examined groups. Manifestations of the viral exanthema and enanthema were more commonly and pronounced in children of the III group. Most children (61.8 %) with Epstein-Barr infection in combination with herpesvirus infection type 6 had disturbances in the central nervous system. The lesions of lymphoid tissue occurred in 73 (76.7 %) children and were more prevalent in the 1st and 2nd surveyed groups. The constant symptom of the disease was hepatomegaly. Splenomegaly was observed in 82 (86.7 %) patients. We have noted an increase in the levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the examined children. These changes were more pronounced in children of the 2nd group. Herewith, cytolysis of hepatocytes in most cases among children of all examined groups was not accompanied by hyperbilirubinemia. The jaundice of the skin and mucous membranes occurred only in 18.5% of all examined patients, who were diagnosed with moderate hyperbilirubinemia (60.0 ± 4.6 μmol/l). Proteinogram parameters in the examined patients in the acute period were characterized by a decrease in albumin content, an increase in the content of α1-, α2- and γ-globulins and a decrease in the albumin / globulin ratio. These indicators were significantly changed in the 2nd surveyed group. The majority of examined patients had coagulogram indices on average matched to the age norm. One third of patients showed moderately elevated fibrinogen levels. Immune disorders, that accompany the herpesvirus infection, are characterized by an imbalance of proinflammatory and anti-inflammatory cytokines. Indicators of portal hemodynamics in patients of the I group in the acute period of the disease were characterized by moderate changes such as a decrease in hepatic artery and portal vein blood flow without viscoelasticity and peripheral vascular resistance violations. In the II group the decrease in the diameter of the common hepatic artery and the increase in the diameter of the portal vein, the decrease in the vessels blood flow with a decrease in their viscoelasticity and peripheral vascular resistance was noted. In the III group of patients the hepatic artery and portal vein hemodynamic changes, which had a compensatory character, were identified. Conclusions: Taking into account the revealed clinical changes, it can be noted that lesions of the nasopharynx, more pronounced manifestations of intoxication and hepatolienal syndromes prevailed in infants with herpesvirus infection. Proinflammatory cytokines overactivity in patients with Epstein-Barr viral infection in combination with cytomegalovirus infection causes a longer intoxication period, pronounced liver enlargement, elevation of transaminases and inhibition of liver albumin synthesis. It could be reasonable to prescribe vasoactive therapy for patients with Epstein-Barr virus infection in combination with cytomegalovirus infection both in the acute and reconvalescence period of the disease followed by structural-functional and hemodynamic state of the liver monitoring at the stages of medical rehabilitation.

Clinical Analysis of Impact of Intraoperative Hepatic Blood Inflow on Acute Kidney Injury following Allogeneic Liver Transplantation

Background Acute kidney injury (AKI) is a major and severe complication following allogeneic liver transplantation and is associated with increased postoperative morbidity and mortality. With proposal of RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) and AKIN (Acute Kidney Injury Network) standards, the diagnosis of AKI has been significantly improved. However, the risk factors and the prognosis factors of AKI remain uncertain, the relativity of intraoperative hepatic blood flow and acute renal injury following liver transplantation hasn't been discussed yet. Method 140 patients who underwent allogeneic liver transplantation at first hospital of China Medical University from January 2006 to October 2016 was analyzed. AKI was diagnosed and graded by AKIN standard. Incidence rate, risk factors, prognosis factors of AKI were investigated. Results Of the 140 cases of allogeneic liver transplantation, the overall incidence rate of AKI was 34.3%(n=48). Multivariate logistic regression analysis showed that preoperative TBil, cold ischemia time, intraoperative RBC infusion unit, intraoperative mean hepatic artery and portal blood flow were risk factors of AKI following liver transplantation. Anhepatic phase was independent risk factor between AKI stage III and AKI stage I /II. Compared with patients whose renal function was fully recovered in 30 days following allogeneic liver transplantation, postoperative TBil, postoperative MELD score, AKI stage III and postoperative CRRT were significantly higher and intraoperative minimum, mean, maximum portal blood flow were obviously lower in patients whose renal function was partially recovered. Conclusion Incidence rate of AKI following liver transplantation is relatively high, and is closely related to multiple perioperative risk factors such as intraoperative blood flow of hepatic artery and portal vein. Anhepatic phase is the independent risk factor of sever AKI and the early recovery of renal function is worse in patients with lower intraoperative portal blood flow.

Compartment model analysis of intravenous contrast-enhanced dynamic computed tomography in hepatic hemodynamics: A validation study using intra-arterial contrast-enhanced computed tomography.

To verify the utility of the 2-in-1-out-compartment model analysis (CMA) of intravenous contrast-enhanced dynamic computed tomography (IV-CT) for evaluating hepatic arterial and portal venous flow using intra-arterial contrast-enhanced CT (IA-CT). We retrospectively evaluated 49 consecutive patients who underwent IV-CT and were radiologically or histologically diagnosed as having hepatic malignant lesion (51 classical hepatocellular carcinomas [HCC], 4 early HCC, 3 cholangiolocellular carcinomas, 1 mixed HCC, 3 cholangiocellular carcinomas). As a gold standard for hepatic arterial and portal blood flows, we defined the normalized enhancement in CT values on CTAP (nCTAP) and CTHA (nCTHA). The hepatic arterial (k1a ) and portal venous inflow velocity (k1p ) constants in hepatic lesions and surrounding liver parenchyma were obtained from the CMA of IV-CT with various outflow velocity constant (k2 ) limits using the nonlinear least square method. The correlation coefficient between the normalized enhancement in IA-CT and CMA of IV-CT was statistically evaluated according to various k2 limits. The highest mean correlation coefficient between k1a and nCTHA (r = 0.65, P < 0.0001) was observed when k2 ≦0.035. The highest mean correlation coefficient between k1p and nCTAP (r = 0.69, P < 0.0001) was observed when k2 ≦0.045. The decrease in correlation coefficient was significant when the upper k2 limit was lower than 0.03 or higher than 0.07 compared to the best mean correlation coefficient (P < 0.05). Hepatic arterial and portal venous flows can be evaluated quantitatively to some extent with appropriate outflow velocity constant limits using the CMA of IV-CT.