Measurement Of Hepatic Blood Flow Research Articles

Different methods for hepatic flow measurements: a narrative review

Hepatic blood flow measurement constitutes an essential tool for successful hepatic surgery, especially in situations where graft patency needs to be controlled, such as for instance during and after liver transplantation. In addition, because of its complex intrinsic regulation, the hepatic circulation may be seriously affected in the perioperative setting not only because of systemic hemodynamic alterations but also secondary to the administration of various drugs including anesthetic agents. Unravelling and understanding such effects implies studies involving measurement of hepatic blood flow. Therefore, knowledge and understanding of various tools for estimation of hepatic blood flow is important for correct interpretation of findings from experimental and clinical studies before potential implementation in daily clinical practice. This review summarizes the different techniques, their strengths and limitations, and potential applications in clinical practice and research.

10 Preliminary Effect of Cottonseed as a Source of Gossypol on Hepatic Portal Blood Flow as an Indicator of Metabolism in Meat does Artificially Infected withHaemonchus Contortus

Abstract Cottonseed diets provide animals with increased levels of protein and energy to support growth. Recently, it was suggested that although the gossypol content of cottonseed could result in adverse animal reproduction, it could have a potential anthelmintic property beneficial to small ruminant operations. In addition, gossypol is primarily cleared and excreted from the animal via liver glucuronidation, which is a primary pathway for steroid clearance in ruminants. The objective of this experiment was to determine the effect of a cottonseed diet and parasite load on the hepatic portal blood flow an indicator of hepatic clearance rates and metabolism. Forty Boer x Spanish cross does were assigned to of 4 treatments (n = 10 per treatment group) in a 2x2 factorial design consisting of cottonseed supplementation and no parasite infection (CNP), cottonseed supplementation plus artificial infection with Haemonchus contortus (CP), commercial pellets with no parasite infection (NCNP), or commercial pellets plus artificial infection with Haemonchus contortus (NCP). On week 8 post-treatment, hepatic portal blood flow measurements were collected via Doppler ultrasonography on the right side of the animal at the 10th intercostal space. Blood flow was then calculated using the following equation: blood flow (mL/min) = mean velocity (cm/s) x vessel area x 60 seconds. The mean velocity was calculated by the following formula: (systolic – diastolic)/pulsatility index. Hepatic portal blood flow and body weight of does were analyzed with a One-way ANOVA using the MIXED procedure of SAS with diet and parasite load as the main effects and their interactions. A diet by parasite interaction (P = 0.026) was observed for the mean velocity of the hepatic portal vein, which was decreased in CP versus CNP treatments. A diet by parasite interaction (P = 0.012) was observed for the diameter of the hepatic portal vein, which was increased in the CP treatment versus all other groups. However, absolute hepatic portal blood flow was not different (P > 0.12) amongst treatments. A tendency for the main effect (P = 0.087) of diet was observed for hepatic portal blood flow relative to body weight, which was an increase in cottonseed (27.8 ±.8 mL/min*kg) versus NCS (23.2 ±.8 mL/min*kg). Body weight was not different (P > 0.35) amongst treatments at the time of Doppler ultrasound examination. In conclusion, cottonseed interacted with parasites to decrease mean velocity and increase the diameter of the portal vein. In addition, cottonseed appears to increase liver blood flow relative to body weight. This change in relative liver blood flow could have implications for mediating hepatic metabolism and clearance.

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

BackgroundNorepinephrine (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.MethodsPatients 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.ResultsA 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).ConclusionAdministration 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 registrationStudy protocol EC: 2019/0395.EudraCT n°: 2018–004,139-66 (25 – 03 – 2019).Clin.trail.gov: NCT03965117 (28 – 05 – 2019).

Hepatic blood flow in adult Göttingen minipigs and pre-pubertal Danish Landrace x Yorkshire pigs.

The liver receives dual blood supply from the hepatic artery and portal vein. The pig is often used as an animal model in positron emission tomography (PET) and pharmacokinetic studies because of the possibility for extensive and direct blood sampling. In this study, we compared measurements of hepatic blood flow in 10 female adult Göttingen minipigs and 10 female pre-pubertal Danish Landrace x Yorkshire (DLY) pigs. Ultrasound transit time flow meter probes were placed around the hepatic artery and portal vein through open surgery, hepatic blood flow measurements were performed, and the liver was weighed. Total hepatic blood flow was on average 363 ± 131 mL blood/min in Göttingen minipigs and 988 ± 180 mL blood/min in DLY pigs (p < 0.001). The mean hepatic blood perfusion was 623 mL blood/min/mL liver tissue and 950 mL blood/min/mL liver tissue (p = 0.005), and the liver weight was 0.58 kg and 1.04 kg, respectively. The mean arterial flow fraction in Göttingen minipigs was 12 ± 7% and lower than in DLY pigs, where it was 24 ± 7% (p = 0.001). Using the gold standard for blood flow measurements, we found that both total hepatic blood flow and blood perfusion were significantly lower in Göttingen minipigs than in DLY pigs. The hepatic blood perfusion and arterial flow fraction in DLY pigs were comparable to normative values from humans. Differences in hepatic blood flow between adult Göttingen minipigs and humans should be considered when performing physiological liver studies in this model.

Doppler characteristics of hepatic venous hemodynamics in adult healthy camels (Camelus dromedarius)

Abstract The present study was designed to describe the Doppler measurements of hepatic venous blood flow in camels (Camelus dromedarius). A total number of 9 adult healthy camels underwent hepatic Doppler examinations on the right side between the 11th and 9th intercostal spaces. The splenic and cranial mesenteric veins showed turbulent blood flows at their fusion to form the main portal trunk. At porta hepatis, the main portal vein exhibited turbulent blood flows and the mean velocities ranged from 21 to 28 cm/sec. In contrast, the intrahepatic branches of portal veins revealed smooth laminar spectral patterns with low blood velocities ranged from 12 to 22 cm/sec. In addition, hepatic veins and caudal vena cava have laminar blood flows. In conclusion, as a non-invasive clinical tool, Doppler ultrasonography is a simple and easy applicable method for assessment of hepatic hemodynamics in camels (Camelus dromedaries). The present findings have the potential to serve as references for evaluating the health status of the liver from camels. Therefore; a further research study, including comparative evaluation of Doppler findings in camels with various hepatic diseases, may be required.

Role of Measurement of Hepatic Hemodynamics by Triphasic CT in the Evaluation of Patients with Liver Cirrhosis

AbstractBackground: Liver biopsy has been the main method for diagnosis, but it is an invasive method, with many complica-tions, so a non-invasive method is needed to assess the severity of liver cirrhosis.Aim of Study: To assess the severity of liver cirrhosis by measurement of hepatic blood flow using triphasic CT.Patients and Methods: Our case control, single centre study involved 30 patients with chronic diffuse parenchymatous liver disease (which were further divided into Child-Pugh A, B, and C subgroups) and 30 healthy volunteers. All cases underwent supervision of their medical history, clinical ex-amination, liver function tests, and triphasic CT scan. Meas-urement of contrast enhancement fraction (CEF) as a parameter of hepatic blood flow was calculated using triphasic CT, assessment of ROI (region of interest) in HU for the hepatic parenchyma in both arterial and venous phases were done. The contrast enhancement (CEF) was obtained by dividing the contrast concentration in the hepatic arterial phase by that in the portal venous phase using ROI measurement in HU. CEF values and the ROI measurements from the study and control groups were compared.Results: The differences in the ROI measurements were statistically significant between the subgroups with multiple comparisons, except between the control and the Child-Pugh (A) group. The ROI measurement in the portal phase was higher than that measured in the hepatic arterial phase in both the study and control groups. There was a decrease in ROI measurement in both the arterial and portal phases with increase of the Child-Pugh grade; more evident in the portal phase. The value of CEF in the control group was 0.74. The CEF values increased with increasing Child-Pugh grades in the study group. There were noticeable differences for CEF between Child-Pugh A and B groups, Child-Pugh A and C groups and Child-Pugh B and C groups. The CEF increased as liver function (Child-Pugh grade) deteriorated in the study group.Conclusion: Measurement of hepatic blood flow and CEF by using triphasic CT can be used to evaluate the liver hemo-dynamics and severity of liver cirrhosis.

Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

BackgroundThe hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound (TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI (PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. MethodsEighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery (Qha), the portal vein (Qpv), and the aorta above the celiac trunk (Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression (PLS) model was implemented. ResultsThe mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32% (95% CI: −49% to 15%); Qha 17% (95% CI: −15% to 51%); and Qpv 40% (95% CI: −62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI (β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively). ConclusionsThere is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.

Dynamic Measurement of Arterial Liver Perfusion With an Interventional C-Arm System.

Objective intraprocedural measurement of hepatic blood flow could provide a quantitative treatment end point for locoregional liver procedures. This study aims to validate the accuracy and reproducibility of cone-beam computed tomography perfusion (CBCTp) measurements of arterial liver perfusion (ALP) against clinically available computed tomography perfusion (CTp) measurements in a swine embolization model. Triplicate CBCTp measurements using a selective arterial contrast injection were performed before and after complete embolization of the left lobe of the liver in 5 swine. Two CBCTp protocols were evaluated that differed in sweep duration (3.3 vs 4.5 seconds) and the number of acquired projection images (166 vs 248). The mean ALP was measured within identical volumes of interest selected in the embolized and nonembolized regions of the perfusion map generated from each scan. Postembolization CBCTp values were also compared with CTp measurements. The 2 CBCTp protocols demonstrated high concordance correlation (0.90, P < 0.001). Both CBCTp protocols showed higher reproducibility than CTp in the nontarget lobe, with an intraclass correlation of 0.90 or greater for CBCTp and 0.83 for CTp (P < 0.001 for all correlations). The ALP in the embolized lobe was nearly zero and hence excluded for reproducibility. High concordance correlation was observed between the CTp and each CBCTp protocol, with the shorter CBCTp protocol reaching a concordance correlation of 0.75 and the longer achieving 0.87 (P < 0.001 for both correlations). Dynamic blood flow measurement using an angiographic C-arm system is feasible and produces quantitative results comparable to CTp.

Antifibrotic Effects of Carvedilol and Impact of Liver Fibrosis on Carvedilol Pharmacokinetics in a Rat model.

Carvedilol is a drug of choice in treatment of portal hypertension. The present study was designed to elucidate the potential role of antifibrotic effects of carvedilol in improving hepatic efficiency and the carvedilol oral pharmacokinetic changes during induction of liver fibrosis. Rats were given CCl4 (1ml/kg, intraperitoneal) twice weekly for 6weeks and/or co-treated with carvedilol (10mg/kg, orally) three times weekly on alternating days. Indocyanine green (ICG) clearance test was used as a modality for the measurement of hepatic blood flow. In addition, assessment of serum albumin as a marker of synthetic capacity and immunohistochemical staining of P-glycoprotein (P-gp) expression as a marker of metabolic capacity were done. Furthermore, hydroxyproline and TGF-β1 were detected as markers of liver fibrosis. The area under plasma concentration-time curve of a single dose of carvedilol was significantly increased, associated with decreased the clearance in rats intoxicated with CCl4 compared to control group. Carvedilol co-treatment in CCl4-intoxicated rats for 6weeks significantly counteracted the changes in hepatotoxicity markers and histopathological lesions induced by CCl4. In addition, there were no significant alterations in carvedilol pharmacokinetics between control and CCl4-intoxicated rats. Furthermore, carvedilol treatment restored liver efficiency, including synthetic and metabolic capacity as well as hepatic blood flow. The present study provides evidence underlying the antifibrotic effects of carvedilol and enhancement of hepatic efficiency. In addition, the pharmacokinetic parameters of a single dose of carvedilol are altered in liver fibrosis, manifested as delayed clearance. This was attributed to the reduction of both hepatic blood flow and CYP2D6 expression in the liver. Carvedilol co-treatment in CCl4-intoxicated rats for 6weeks recovered its pharmacokinetic profile, which is mainly attributed to the impact of pharmacodynamic antifibrotic effects of carvedilol on its own kinetics.

The Lumped Constant for the Galactose Analog 2-18F-Fluoro-2-Deoxy-d-Galactose Is Increased in Patients with Parenchymal Liver Disease

The galactose analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) is a suitable PET tracer for measuring hepatic galactokinase capacity in vivo, which provides estimates of hepatic metabolic function. As a result of a higher affinity of galactokinase toward galactose, the lumped constant (LC) for (18)F-FDGal was 0.13 in healthy subjects. The aim of the present study was to test the hypothesis of a significantly different LC for (18)F-FDGal in patients with parenchymal liver disease. Nine patients with liver cirrhosis were studied in connection with a previous study with determination of hepatic intrinsic clearance of ¹⁸F-FDGal (V*(max/K*(m)). The present study determined the hepatic removal kinetics of galactose, including hepatic intrinsic clearance of galactose (V(max)/K(m)) from measurements of hepatic blood flow and arterial and liver vein blood galactose concentrations at increasing galactose infusions. LC for ¹⁸F-FDGal was calculated as (V*(max)/K*(m))/(V(max)/K(m)). On a second day, a dynamic ¹⁸-FDGal PET study with simultaneous infusion of galactose (mean arterial galactose concentration, 6.1 mmol/L of blood) and blood samples from a radial artery was performed, with determination of hepatic systemic clearance of ¹⁸F-FDGal (K*(+gal) from linear analysis of data (Gjedde-Patlak method). The maximum hepatic removal rate of galactose was estimated from ¹⁸F-FDGal PET data (V(max)(PET)) using the estimated LC. The mean hepatic V(max) of galactose was 1.18 mmol/min, the mean K(m) was 0.91 mmol/L of blood and the mean V(max)/K(m) was 1.18 L of blood/min. When compared with values of healthy subjects, K(m) did not differ (P = 0.77), whereas both V(max) and V(max)/K(m) were significantly lower in patients (both P < 0.01). Mean LC for ¹⁸LF-FDGal was 0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects (P < 0.0001). Mean K*(+gal) determined from the PET study was 0.019 L of blood/min/L of liver tissue, which was not significantly different from that in healthy subjects (P = 0.85). Mean hepatic V(max)(PET) was 0.57 mmol/min/L of liver tissue, which was significantly lower than the value in healthy subjects (1.41 mmol/min/L of liver tissue (P < 0.0001). Disease may change the LC for a pet tracer, and this study demonstrated the importance of using the correct LC.

Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C

AimsThe present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C).MethodsXe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined.ResultsIn group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C.ConclusionsPVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

“Small-for-flow” syndrome: Shifting the “size” paradigm

The “small-for-size” syndrome and “post-hepatectomy liver failure” refers to the development of liver failure (hyperbilirubinemia, coagulopathy, encephalopathy and refractory ascites) resulting from the reduction of liver mass beyond a certain threshold. This complication is associated with a high mortality and is a major concern in liver transplantation involving reduced liver grafts from deceased and living donors as well as in hepatic surgeries involving extended resections of liver mass. The limiting threshold for liver resection or transplantation is currently predicted based on the mass of the remnant liver (or donor graft) in relation to the body weight of the patient, with a ratio above 0.8 being considered safe. This approach, however, has proved inaccurate, because some patients develop the “small-for-size” syndrome despite complying with the “safe” threshold while other patients who surpass the threshold do not develop it.We hypothesize that the development of the “small-for-size” syndrome is not exclusively determined by the ratio of the mass of the liver remnant (or graft) to the body weight, but it is instead strictly determined by the hemodynamic parameters of the hepatic circulation. This hypothesis is based in recent clinical and experimental reports showing that relative portal hyperperfusion is a critical factor in the development of the “small-for-size” syndrome and that maneuvers that manipulate the hepatic vascular inflow are able to prevent the development of the syndrome despite liver-to-body weight ratios well below the “limiting” threshold. Measurements of hepatic blood flow and pressure, however, are not routinely performed in hepatic surgeries.Focusing on the “flow” rather than in the “size” may improve our understanding of the pathophysiology of the “small-for-size” syndrome and “post-hepatectomy liver failure” and it would have important implications for the clinical management of patients at risk. First, hepatic hemodynamic parameters would have to be measured in hepatic surgeries. Second, these parameters (in addition to liver mass) would be the principal basis for deciding the “safe” threshold of viable liver parenchyma. Third, the hepatic hemodynamic parameters are amenable to manipulation and, consequently, the “safe” threshold may also be manipulated. Shifting the paradigm from “small-for-size” to “small-for-flow” syndrome would thus represent a major step for optimizing the use of donor livers, for expanding the indications of hepatic surgery, and for increasing the safety of these procedures.

Hepatic blood flow plays an important role in ischemia-reperfusion injury

Severe ischemia/reperfusion (IR) injury is associated with poor hepatic microperfusion. The aim of this study was to investigate the role of hepatic artery flow (HAF) and portal vein flow (PVF) in IR injury. From January 2004 to June 2008, 566 patients underwent orthotopic liver transplantation (OLT). The data were retrospectively reviewed via the transplant database. Patients with hepatic artery (HA) or portal vein (PV) thrombosis and retransplant patients were excluded. Intraoperative PVF and HAF values and graft weights were measured routinely, and the central venous pressure, mean arterial pressure, cardiac output, and cardiac index were recorded with hepatic blood flow measurements. Complete data were available for 312 primary OLT recipients (215 males and 97 females; mean age = 54 ± 10 years). The patients' follow-up ranged from 215 to 1746 days (705 ± 408 days). IR injury was defined by the aspartate aminotransferase (AST) level on postoperative day (POD) 2, and the patients were divided into 3 groups: (1) mild IR injury [AST < 500 U/L; n = 160 (51%)], (2) moderate IR injury [AST = 500-1000 U/L; n = 85 (27%)], and (3) severe IR injury [AST > 1000 U/L; n = 67 (21%)]. The demographics and pre-OLT variables (the Model for End-Stage Liver Disease score (MELD), platelet counts, PV thrombosis, transjugular intrahepatic portosystemic shunts, and shunts on computed tomography scans) were similar in all groups. The graft survival rate was 99% in group 1, 95.2% in group 2 (P = 0.02), and 92.3% in group 3 (P = 0.016). The patient survival rates were similar in the 3 groups. The cold ischemia time (CIT) was significantly higher in group 3 versus group 1 (P < 0.007). In the statistical analysis, low HAF, PVF, total liver blood flow (TLBF), and augmented HAF values were associated with a greater likelihood of elevated AST levels on POD 2. The strongest univariate predictors of AST were reduced augmented HAF (mL/minute/100 g) values (P < 0.001) and reduced TLBF (mL/minute/100 g) values (P < 0.001). In a covariate analysis with adjustments for CIT and donor variables, the blood flow parameters remained important predictors of graft function. In conclusion, this report demonstrates for the first time that reduced hepatic blood flow is a significant finding in patients with severe hepatic IR injury.

Hepatic Galactose Metabolism Quantified in Humans Using 2-18F-Fluoro-2-Deoxy-d-Galactose PET/CT

Accurate quantification of regional liver function is needed, and PET of specific hepatic metabolic pathways offers a unique method for this purpose. Here, we quantify hepatic galactose elimination in humans using PET and the galactose analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) as the PET tracer. Eight healthy human subjects underwent (18)F-FDGal PET/CT of the liver with and without a simultaneous infusion of galactose. Hepatic systemic clearance of (18)F-FDGal was determined from linear representation of the PET data. Hepatic galactose removal kinetics were determined using measurements of hepatic blood flow and arterial and liver vein galactose concentrations at increasing galactose infusions. The hepatic removal kinetics of (18)F-FDGal and galactose and the lumped constant (LC) were determined. The mean hepatic systemic clearance of (18)F-FDGal was significantly higher in the absence than in the presence of galactose (0.274 ± 0.001 vs. 0.019 ± 0.001 L blood/min/L liver tissue; P < 0.01), showing competitive substrate inhibition of galactokinase. The LC was 0.13 ± 0.01, and the (18)F-FDGal PET with galactose infusion provided an accurate measure of the local maximum removal rate of galactose (V(max)) in liver tissue compared with the V(max) estimated from arterio-liver venous (A-V) differences (1.41 ± 0.24 vs. 1.76 ± 0.08 mmol/min/L liver tissue; P = 0.60). The first-order hepatic systemic clearance of (18)F-FDGal was enzyme-determined and can thus be used as an indirect estimate of galactokinase capacity without the need for galactose infusion or knowledge of the LC. (18)F-FDGal PET/CT provides an accurate in vivo measurement of human galactose metabolism, which enables the quantification of regional hepatic metabolic function.

Direct measurement of hepatic blood flow during living donor liver transplantation in children

Background The changes in liver blood flow associated with living donor liver transplantation (LDLT) in children have not yet been studied. The aim of the present study was to investigate changes in hepatic hemodynamics before and after pediatric partial liver transplantation. Methods In 7 pediatric recipients with congenital cholestasis and native liver Child-Pugh classes B and C, portal vein flow (PVF) and hepatic arterial flow (HAF) were measured using an ultrasonic transit time flow meter before removal of the native liver and after transplantation and compared with donor left PVF and donor left HAF. Results The mean portal contribution to total hepatic blood flow was markedly decreased in the recipient native liver compared with that in the donor (69% ± 15% vs 32% ± 15%; P = .0003) and after reperfusion changed to almost the same ratio as that in the donor liver (73% ± 18%; P < .0001). Conclusion The extreme imbalance between PVF and HAF that is common in implanted partial liver in adult LDLT recipients was not observed in pediatric LDLT. After transplantation of an appropriately sized liver graft, the portal contribution to total liver blood flow normalized to the value for normal liver.

Hepatic vascular flow measurements by phase contrast MRI and doppler echography: A comparative and reproducibility study

To directly compare and study the variability of parameters related to hepatic blood flow measurements using 3 T phase-contrast magnetic resonance imaging (PC-MRI) and Doppler ultrasound (US). Nine healthy subjects were studied. Blood velocities and flow rate measurements were performed in the portal vein and the proper hepatic artery. MR studies were performed using a 3 T imager. Gradient-echo fast phase contrast sequences were used with both cardiac and respiratory gating. MR and Doppler flow parameters were extracted and compared. Two methods of calculation were used for Doppler flow rate analysis. Compared to Doppler US, PC-MRI largely underestimated hepatic flow data with lower variability and higher reproducibility. This reproducibility was more pronounced in the portal vein than in the proper hepatic artery associated with poorer velocity correlations. Total hepatic flow values were 1239 +/- 223 mL/min and 1595 +/- 521 mL/min for PC-MRI and Doppler US, respectively. Free-breathing PC-MRI can provide reliable noninvasive measurement of hepatic flow parameters compared to Doppler US. The MR technique could help to improve Doppler flow calculations, thereby allowing standardization of protocols, particularly for applications in disease.

Hepatic ethanol elimination kinetics in patients with cirrhosis

Objective. To address the question of whether increased ethanol elimination in alcoholics can be ascribed to increased metabolism via alcohol dehydrogenase (ADH; Km around 0.2 mM) or the microsomal ethanol-oxidizing system (MEOS; Km 10 mM) by kinetic analysis of hepatic ethanol elimination in recently drinking patients with alcoholic cirrhosis and healthy subjects. A further objective was to investigate whether systemic clearance of ethanol at low arterial ethanol concentrations can be used as a measure of hepatic blood flow. Material and methods. Six patients with alcoholic cirrhosis were enrolled after 2 days of abstinence, along with 6 healthy subjects. Ethanol was administered as 6 successive infusions in increasing doses. Arterial and hepatic venous blood concentrations of ethanol were measured; hepatic blood flow was measured simultaneously. Kinetic parameters were calculated according to the sinusoidal perfusion model of enzymatic elimination by the intact liver. Results. Mean hepatic Km for ethanol was 0.16 mM (range 0.09–0.36) in healthy subjects and 0.36 mM (range 0.16–0.69) in patients with cirrhosis (p>0.3), both compatible with the Km for ADH. The two groups of subjects had similar Vmax values (p>0.3). Extrahepatic elimination of ethanol accounted for more than 50% of total elimination in both groups, which precludes the use of systemic clearance as a measure of hepatic blood flow. Conclusions. The results support the hypothesis that ADH remains the main pathway for hepatic elimination of ethanol in recently drinking patients with alcoholic cirrhosis. We interpret this as evidence against a significant contribution of MEOS in vivo.

Dynamic measurements of total hepatic blood flow with Phase Contrast MRI

Background/Aims To measure total hepatic blood flow including portal and proper hepatic artery flows as well as the temporal evolution of the vessel's section during a cardiac cycle. Methods Twenty healthy subjects, with a mean age of 26 years, were explored. Magnetic resonance imaging blood flow measurements were carried out in the portal vein and the proper hepatic artery. MR studies were performed using a 1.5T imager (General Electric Medical Systems). Gradient-echo 2D Fast Cine Phase Contrast sequences were used with both cardiac and respiratory gatings. Data analysis was performed using a semi-automatic software built in our laboratory. Results The total hepatic flow rate measured was 1.35 ± 0.18 L/min or 19.7 ± 4.6 mL/(min kg). The proper hepatic artery provided 19.1% of the total hepatic blood flow entering the liver. Those measurements were in agreement with earlier studies using direct measurements. Mean and maximum velocities were also assessed and a discrepancy between our values and the literature's Doppler data was found. Measurements of the portal vein area have shown a mean variation, defined as a “pulsatility” index of 18% over a cardiac cycle. Conclusions We report here proper hepatic artery blood flow rate measurements using MRI . Associated with portal flow measurements, we have shown the feasibility of total hepatic flowmetry using a non-invasive and harmless technique.

Distinct roles of free leptin, bound leptin and soluble leptin receptor during the metabolic‐inflammatory response in patients with liver cirrhosis

Alteration of the leptin system appears to play a role in the inflammatory-metabolic response in catabolic diseases such as chronic liver diseases. To investigate the association between leptin components, inflammatory markers and hepatic energy and substrate metabolism. We investigated in vivo hepatic substrate and leptin metabolism in 40 patients employing a combination of arterial and hepatic vein catheterization techniques and hepatic blood flow measurements. In addition to metabolic, inflammatory and neuroendocrine parameters, circulating levels of free leptin, bound leptin and soluble leptin receptor were determined. Compared with controls, bound leptin and soluble leptin receptor levels were significantly elevated in cirrhosis, while free leptin did not increase. In cirrhosis bound leptin was correlated with soluble leptin receptor (r = 0.70, P < 0.001). Free leptin was positively correlated with metabolic parameters such as energy storage (body fat mass; r = 0.36, P < 0.05), insulin and insulin resistance (r = 0.48; r = 0.46, P < 0.01) as well as with hepatic glucose and energy release (r = 0.35 and r = 0.40, P < 0.05). In contrast, bound leptin and soluble leptin receptor were linked to proinflammatory cytokines and sympathetic activity (r = 0.61 and r = 0.56, P < 0.01). The components of the leptin system (free leptin, bound leptin and soluble leptin receptor) have distinct roles in metabolic and inflammatory processes in patients with liver cirrhosis. The better understanding of this metabolic and inflammatory tissue-repair response may lead to innovative new therapeutic strategies in liver disease as well as in various other catabolic diseases.

Quantitative Tissue Blood Flow Measurement of the Liver Parenchyma: Comparison Between Xenon CT and Perfusion CT

The purpose of this study was to compare measurements of hepatic tissue blood flow (TBF) calculated by xenon and perfusion CT. Seven patients with normal liver and eight with chronic liver disease underwent both xenon and perfusion CT. During xenon CT examinations, serial abdominal CT scans were obtained every minute before and during 4 min of nonradioactive 25% (v/v) xenon gas inhalation and 5 min of administration of oxygen-rich air. Hepatic arterial and portal venous TBF were measured separately with a special imaging system using the Kety-Schmidt expression based on the Fick principle (AZ-7000W; Anzai Medical Co.). The hepatic arterial fraction (HAF) was calculated as follows: [hepatic arterial TBF/(hepatic arterial TBF + portal venous TBF)]. During perfusion CT examinations, total hepatic TBF and HAF were also calculated from the enhanced CT cine image data on a workstation using a commercially available software package based on a deconvolution algorithm (CT Perfusion 3 GE Healthcare, USA). Total hepatic TBF measured by xenon and perfusion CT was 82.9+/-15 and 82.8+/-18 ml/min/100 g, respectively. The measured values by the two techniques showed a significant correlation (R (2)= 0.657, P < 0.05). HAF measured by xenon and perfusion CT was 26.6+/-11 and 21.8+/-13%, respectively. The measured values by the two techniques also showed a significant correlation (R (2)= 0.869, P < 0.05). We conclude that there was a good correlation between hepatic TBF quantified by xenon CT and perfusion CT.