Hepatic Venous Blood Research Articles

Quantifying and visualizing abdominal hemodynamics in patients with Fontan circulation by 4D phase-contrast flow magnetic resonance imaging at 1.5 T

BackgroundLiver fibrosis has been recognized as a long-term morbidity associated with Fontan circulation (Fontan-associated liver disease, FALD). The pathophysiology of FALD is not completely understood and abnormal flow dynamics may be associated with this condition. Liver hemodynamics can be quantitatively evaluated with four-dimensional phase-contrast flow magnetic resonance imaging (4D PC flow MRI). The study aimed to evaluate suitability of liver 4D PC flow MRI in Fontan patients and relate flow measurements to normal values and FALD severity. Patients and methodsTwenty-two Fontan patients were examined by 4D PC flow MRI at 1.5 Tesla to assess mesenteric, portal, splenic, and hepatic venous blood flow. Severity of FALD was graded based on routine screening, including abdominal ultrasound and laboratory tests. ResultsMedian age was 18.5 (interquartile range, IQR 15.5–20.2) years. FALD was graded as “none or mild” in 16 and as “moderate to severe” in six cases. Ten patients presented at least one feature of portal hypertension (ascites, splenomegaly, or thrombocytopenia). For the entire cohort, blood flow in the superior mesenteric, splenic, and portal vein was lower than reported in the literature. No significant differences were observed in relation to FALD severity. Features of portal hypertension were associated with a higher splenic vein blood flow (0.34 ± 0.17 vs. 0.20 ± 0.07 l/min, p = 0.046). Splenic vein blood flow was negatively correlated to platelet count (r = −0.590, p = 0.005). Conclusions4D PC flow MRI appears suitable to assess liver hemodynamics in Fontan patients and integration into clinical follow-up might help to improve our understanding of FALD.

Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation-related markers.

Frequent binge drinking is a known contributor to alcohol-related harm, but its impact on systemic and hepatic inflammation is not fully understood. We hypothesize that changes in immune markers play a central role in adverse effects of acute alcohol intake, especially in patients with early liver disease. To investigate the effects of acute alcohol intoxication on inflammation-related markers in hepatic and systemic venous plasma in people with alcohol-related liver disease (ArLD), non-alcoholic fatty liver disease (NAFLD) and healthy controls. Thirty-eight participants (13 with ArLD, 15 with NAFLD and 10 healthy controls) received 2.5 mL of 40% ethanol per kg body weight via a nasogastric tube. Seventy-two inflammation-related markers were quantified in plasma from hepatic and systemic venous blood, at baseline, 60 and 180 min after intervention. Alcohol intervention altered the levels of 31 of 72 and 14 of 72 markers in the systemic and hepatic circulation. All changes observed in the hepatic circulation were also identified in the systemic circulation after 180 min. Only FGF21 and IL6 were increased after alcohol intervention, while the remaining 29 markers decreased. Differences in response to acute alcohol between the groups were observed for 8 markers, and FGF21 response was blunted in individuals with steatosis. Acute alcohol intoxication induced changes in multiple inflammation-related markers, implicated in alcohol metabolism and hepatocellular damage. Differences identified between marker response to binge drinking in ArLD, NAFLD and healthy controls may provide important clues to disease mechanisms and potential targets for treatment. NCT03018990.

Heparin reversal with protamine sulfate after Percutaneous Hepatic Perfusion (PHP): is less more?

PurposePercutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP.Materials and methodsAll patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (groupPROTAMINE); 13 patients/21 PHP in groupREDUCED_PROTAMINE received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (groupNO_PROTAMINE). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0).ResultsThromboembolic events were recorded after 10 PHP procedures (5%) in groupPROTAMINE, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in groupREDUCED_PROTAMINE and groupNO_PROTAMINE. Hemorrhagic events were registered after 24 PHP (13%) in groupPROTAMINE, two of which (1%) were major (CTCAE grade 3-4). In groupREDUCED_PROTAMINE, only minor bleeding events were recorded, and one major hemorrhagic event was documented in groupNO_PROTAMINE (2%). There was a significant difference between the percentage of post-interventional thrombopenia in groupPROTAMINE (39%) and groupREDUCED_PROTAMINE (14%) versus groupNO_PROTAMINE (23%) (p=.00024). In groupPROTAMINE one patient suffered from a severe anaphylactic shock after the administration of protamine.ConclusionOur retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.

Anesthesiological and postinterventional management in percutaneous hepatic melphalan perfusion (chemosaturation)

Percutaneous hepatic melphalan perfusion (PHMP) is alast-line treatment of inoperable primary or secondary liver tumors. Selective perfusion and saturation (chemosaturation) of the liver with the chemotherapeutic agent melphalan is performed via catheterization of the hepatic artery without affecting the rest of the body with its cytotoxic properties. Using an extracorporeal circulation and balloon occlusion of the inferior vena cava, the venous hepatic blood is filtered and returned using abypass procedure. During the procedure, considerable circulatory depression and coagulopathy are frequent. The purpose of this article is to review the anesthesiological and postprocedural management of patients undergoing PHMP with consideration of the pitfalls and special circumstances.

A O03 Ex vivo perfusion of isolated human liver segments: the development of a novel model for ethical, translational research

Abstract Background Ex vivo perfusion techniques for human organs, in particular for the human liver, have been extensively studied for decades. Although ex vivo perfusion of human organs has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Not only do these models allow more accurate study of human organ response to noxious external stimuli, but they also represent a far more ethical alternative to live animal experimentation.Although split-liver perfusion of the left or right hepatic lobe is well described in literature, ex vivo perfusion of isolated liver segments has not been previously attempted. A successful hepatic segmental perfusion model would provide a unique opportunity to study inflammation, response to infection and novel therapeutic approaches.The overall aim of this study was to establish an experimental ex vivo hepatic perfusion model on surgically resected human liver segments as a platform to evaluate and study organ preservation and function. The development of an ex vivo perfusion model of human liver segments would produce the ideal platform to study treatment effects without needing to sacrifice animals. Methods Patients were recruited as part of the TIMOLD (Tissue Models for Liver Disease) clinical trial (ClinicalTrials.gov Identifier: NCT05255042; 8/9/2021). Patients recruited were those aged eighteen or over undergoing elective liver resections at a single hepatobiliary unit. Nine human liver segments were retrieved following hemi-hepatectomy for colorectal liver metastases or hepatocellular carcinoma. A healthy segment was resected from the diseased specimen in theatre and a segmental hepatic artery and portal vein was cannulated immediately and flushed with ice cold heparinised preservation solution. Four segments were perfused with 600ml O negative expired red blood cells (HL-RBC) and five segments were perfused with 250ml Oxyglobin diluted with 250ml Volplex (HL-OXY). All segments were administered several drugs to provide metabolic support and optimise perfusion owing to their anticoagulant, antioxidant, and anti-inflammatory properties. Segments were perfused on a bespoke normothermic machine perfusion circuit for 4–6 hours. Perfusion parameters were monitored throughout perfusion and hourly hepatic venous blood gases were taken to monitor glucose and lactate levels. Hourly core biopsies were also taken for H&E staining and interpreted by a consultant histopathologist. Data is reported as the median (range) and statistical analysis has been performed using the Mann-Whitney U test on Graphpad Prism. Results HL-RBC (n=4) had a median pre-perfusion weight of 216 (146–1330) grams whilst HL-OXY (n=5) had a median weight of 269(128–367) grams (p>0.05). HL-RBC segments had a median warm ischaemic (WI) time of 76.5(68–81) minutes and a median cold ischaemic (CI) time of 97 (35–119) minutes. HL-OXY segments had a median WI time of 5 (3–80) minutes and a median CI time of 38 (28–63) minutes (p>0.05). Median portal venous resistance was lower for the HL-OXY group (0.076mmHg/ml/min) in comparison to the HL-RBC group (0.62mmHg/ml/min); p<0.05. There was no significant difference in hepatic arterial resistance between the two groups (HL-RBC 3 mmHg/ml/min; HL-OXY 2.38 mmHg/ml/min; p>0.05). HL-OXY had a lower median lactate of 4.54mmol/L in comparison to HL-RBC (14.7mmol/L) throughout perfusion (p<0.05). HL-OXY segments also had a lower median glucose of 5.9mmol/L compared to 9.65mmol/L for HL-RBC (p<0.05). 1/4 HL-RBC segments had normal histology after 6 hours of perfusion. 2/4 segments showed evidence of necrosis after 2 hours (one with established cirrhosis), and 1/4 segment demonstrated necrosis after 3 hours of perfusion. 4/5 HL-OXY segments demonstrated normal histology after 6 hours of perfusion. One segment, with known cirrhosis, demonstrated necrosis after two hours of perfusion. Conclusions We present here, for the first time, the development of a successful ex vivo isolated hepatic segmental perfusion model. We demonstrate, in the development of this model, that bovine haemoglobin glutamer-200 (Oxyglobin) is a superior oxygen carrier to expired O negative red blood cells in the ex vivo perfusion of isolated human hepatic segments. The HL-OXY group demonstrated a significantly lower portal venous resistance in comparison to HL-RBC, although there was no difference in arterial resistance. Furthermore, HL-OXY segments had lower median glucose and lactate levels during perfusion compared to HL-RBC segments. 4 of 5 segments perfused with Oxyglobin demonstrated viable hepatocytes on histopathological analysis after 6 hours of perfusion. The segment demonstrating early necrosis was one with established cirrhosis on pre-perfusion histology. We describe a protocol for the successful ex vivo perfusion of non-cirrhotic human hepatic segments. Human liver is routinely resected in tertiary hepatobiliary units and much of the specimen discarded. The paradigm presented here identifies a readily available ethical source of human liver with minimal warm ischaemia. This facilitates optimal conditions for translational research, is cost-effective and avoids animal experimentation.

Virtual treatment planning in three patients with univentricular physiology using computational fluid dynamics-Pitfalls and strategies.

BackgroundUneven hepatic venous blood flow distribution (HFD) to the pulmonary arteries is hypothesized to be responsible for the development of intrapulmonary arteriovenous malformations (PAVM) in patients with univentricular physiology. Thus, achieving uniform distribution of hepatic blood flow is considered favorable. However, no established method for the prediction of the post-interventional hemodynamics currently exists. Computational fluid dynamics (CFD) offers the possibility to quantify HFD in patient-specific anatomies before and after virtual treatment. In this study, we evaluated the potential benefit of CFD-assisted treatment planning.Materials and methodsThree patients with total cavopulmonary connection (TCPC) and PAVM underwent cardiovascular magnetic resonance imaging (CMR) and computed tomography imaging (CT). Based on this imaging data, the patient-specific anatomy was reconstructed. These patients were considered for surgery or catheter-based intervention aiming at hepatic blood flow re-routing. CFD simulations were then performed for the untreated state as well as for different surgical and interventional treatment options. These treatment options were applied as suggested by treating cardiologists and congenital heart surgeons with longstanding experience in interventional and surgical treatment of patients with univentricular physiology. HFD was quantified for all simulations to identify the most viable treatment decision regarding redistribution of hepatic blood flow.ResultsFor all three patients, the complex TCPC anatomy could be reconstructed. However, due to the presence of metallic stent implants, hybrid models generated from CT as well as CMR data were required. Numerical simulation of pre-interventional HFD agreed well with angiographic assessment and physiologic considerations. One treatment option resulting in improvement of HFD was identified for each patient. In one patient follow-up data after treatment was available. Here, the virtual treatment simulation and the CMR flow measurements differed by 15%.ConclusionThe combination of modern computational methods as well as imaging methods for assessment of patient-specific anatomy and flow might allow to optimize patient-specific therapy planning in patients with pronounced hepatic flow mismatch and PAVM. In this study, we demonstrate that these methods can also be applied in patients with complex univentricular physiology and extensive prior interventions. However, in those cases, hybrid approaches utilizing information of different image modalities may be required.

Micro-scale assessment of bone quality changes in adult cadaveric men with congestive hepatopathy.

Congestive hepatopathy (CH) is a chronic liver disease (CLD) caused by impaired hepatic venous blood outflow, most frequently resulting from congestive heart failure. Although it is known that heart failure and CLDs contribute to increased risk for age-related fractures, an assessment of CH-induced skeletal alterations has not been made to date. The aim of our study was to characterize changes in bone quality in adult malecadavers with pathohistologically confirmed CH compared with controls without liver disease. The anterior mid-transverse part of the fifth lumbar vertebral body was collected from 33 adult malecadavers(age range 43-89 years), divided into the CH group (n = 15) and the control group (n = 18). We evaluated trabecular and cortical micro-architecture and bone mineral content (using micro-computed tomography), bone mechanical competence (using Vickers micro-hardness tester), vertebral cellular indices (osteocyte lacunar network and bone marrow adiposity), and osteocytic sclerostin and connexin 43 expression levels (using immunohistochemistry staining and analysis). Deterioration in trabecular micro-architecture, reduced trabecular and cortical mineral content, and decreased Vickers microhardness were noted in the CH group (p < 0.05). Reduced total number of osteocytes and declined connexin 43 expression levels (p < 0.05) implied that harmed mechanotransduction throughout the osteocyte network might be present in CH. Moreover, elevated expression levels of sclerostin by osteocytes could indicate the role of sclerostin in mediating low bone formation in individuals with CH. Taken together, these micro-scale bone alterations suggest that vertebral strength could be compromised in men with CH, implying that vertebral fracture risk assessment and subsequent therapy may need to be considered in these patients. However, further research is required to confirm the clinical relevance of our findings.

THU021 - Alcohol-induced changes of inflammatory markers in hepatic and systemic venous blood in early alcohol-related and non-alcoholic fatty liver disease

THU021 - Alcohol-induced changes of inflammatory markers in hepatic and systemic venous blood in early alcohol-related and non-alcoholic fatty liver disease

Progress in ICP-MS Analysis of Minerals and Heavy Metals in Traditional Medicine.

Aim: This study systematically reviewed the application of ICP-MS and its combined technology in the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, minerals and their preparations (Chinese patent medicine), and biological products. It provides a reference for improving the quality standard of traditional medicine and exploring the effective components, toxic components, and action mechanism of traditional medicine. Materials and Methods: A total of 234 articles related to the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, and minerals and their preparations (Chinese patent medicine) were collected from PubMed, CNKI, Web of Science, VIP, and other databases. They were classified and sorted by the inductively coupled plasma-mass-spectrometry (ICP-MS) method. Results: Of the 234 articles, 154 were about medicinal materials derived from plants, 15 about medicinal materials derived from animals, 9 about medicinal materials derived from minerals, 46 about Chinese patent medicine, 10 about combined technology application, and 3 about drugs being tested after entering the body. From the 154 articles on medicinal materials derived from plants, 76 elements, including Cu, Cd, Pb, As, Cr, Mn, and Hg, were determined, of which the determination of Cu was the most, with 129 articles. Medicinal materials derived from the roots, stems, leaves, flowers, and fruits and seeds of plants accounted for 25.97%, 18.18%, 7.14%, 7.79%, and 14.94%, respectively. Moreover, medicinal materials derived from the whole plants accounted for 14.94%, and other medicinal materials derived from plants and soil accounted for 11.04%. A total of 137 of the tested medicinal materials were from traditional Chinese medicine, accounting for 88.96%, 12 were from Arabic medicine (including Unani), accounting for 7.79%, 2 were from Tibetan medicine of China, and 1 was from Mongolian medicine of China, 1 was from Miao medicine of China, and 1 was from Zhuang medicine of China. In the 15 articles on medicinal materials derived from animals, 49 elements such as Cu, As, Cd, Hg, Se, Pb, and Mn were determined, of which Cu was the most. All the tested medicinal materials belong to traditional Chinese medicine. From the nine articles on medicinal materials derived from minerals, 70 elements such as Fe, Cu, Zn, Al, As, Se, and Na were determined, of which Fe, Cu, and Zn were the most. The tested medicinal materials all belong to traditional Chinese medicine. From the 46 articles on Chinese patent medicine, 62 elements such as Cu, As, Pb, Cd, Hg, Ni, and Cr were determined, of which Cu was the most. Regarding the tested Chinese patent medicine, 38 articles belong to traditional Chinese medicine, 6 to Tibetan medicine, and 2 to Mongolian medicine of China. Three articles determine the content of metal elements in biological samples such as animal hepatic venous blood, abdominal aortic blood, brain, liver, kidney, urine, and feces, and one article determines the content of metal elements in human lung and serum. From the 10 articles combined with liquid chromatography and gas chromatography, 16 elements such as MMA, DMA, AsIII, AsV, AsB, AsC, and AsI3 were determined, of which MMA and DMA were the most. It can realize elemental morphology and isotope analysis. The tested medicinal materials and Chinese patent medicine belong to traditional Chinese medicine. Conclusion: ICP-MS was applied the most in traditional Chinese medicine, followed by Arabic medicine. ICP-MS was used to determine more medicinal materials derived from plants, and Cu was determined the most. The characteristic inorganic element spectrum of medicinal materials can also be established. ICP-MS and its combined technology are widely used in Chinese patent medicine, but the test of biological samples is the least. The information provided in this article can provide a reference for improving the quality standard of traditional medicines and exploring the active ingredients and toxic ingredients and their mechanism of action.

Transcatheter implantation of covered stents serving as extravascular conduits-Proof of a CT-based approach in three cases.

Covered stents perform similar to surgically implanted conduits, although the stents work inside of vessels. We present a computed tomography(CT)-based workflow for the implantation of covered stents as extravascular conduits. We selected three different use cases: 1. Connecting a left-sided partially anomalous drainage of a pulmonary vein to the left atrium. 2. Bypassing an outgrown Dacron conduit in aortic recoarctation. 3. Re-directing hepatic venous blood to the left lung in a Fontan patient with heterotaxy, connecting the innominate vein to the right pulmonary artery like a right-sided cavopulmonary connection. By postprocessing and analyzing CTscans for planning and by the use of long needles under biplane fluoroscopy for the realization of the procedure, we projected and performed the exit of a long needle out of a vessel, the re-entering of a target vessel, and the bridging of the extravascular distance by implantation of covered stents. In all three cases, the covered stents were placed successfully, connecting vessels of 15-50 mm distance from each other with very good hemodynamic results. In one case, two stents were placed consecutively, overlapping each other to accomplish an exact fitting at the connection sites to the native vessels.

High Interleukin-8 Levels Associated With Decreased Survival in Patients With Cirrhosis Following Transjugular Intrahepatic Portosystemic Shunt.

BackgroundSerum cytokines—reflecting systemic inflammation has been associated with the risk of decompensation and mortality in patients with cirrhosis. However, the role of systemic inflammation in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt procedure remains unknown.Patients and MethodsPatients with cirrhosis who received transjugular intrahepatic portosystemic shunt between June 2015 and September 2017 were included. Portal and hepatic venous blood samples were obtained intraoperatively; serum cytokine levels (IL-10, IL-17A, IL-1RA, IL-8, and CXCL10) were measured in 105 patients. Associations with survival and other outcomes during long-term follow-up (median: 1,564 days) were assessed using logistic regression.ResultsIL-17A and CXCL10 levels were higher in the portal than in the hepatic veins, whereas IL-1RA levels were higher in the hepatic than in the portal veins. However, IL-8 or IL-10 levels between hepatic and portal veins showed no differences. Multivariate analysis demonstrated that Child–Pugh scores (P = 0.017, HR: 1.484, 95% CI: 1.072–2.055) and IL-8 level in hepatic veins (P < 0.001, HR: 1.043, 95% CI: 1.019–1.068) were independent predictors for mortality during long-term follow-up, with an optimal cut-off of 5.87 pg/ml for IL-8 in hepatic veins. Patients with hepatic IL-8 levels < 5.87 pg/ml had significantly higher cumulative survival rates (98.4 vs. 72.9% at 1 year, 98.4 vs. 65.3% at 2 years, 96.7 vs. 60.3% at 3 years, 94.2 vs. 60.3% at 4 years; P < 0.0001).ConclusionsIL-8 levels in hepatic veins may reflect liver cirrhosis severity. Elevated IL-8 levels suggest shorter survival in patients receiving TIPS.

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.

Relationship between Hepatic Venous Anatomy and Blood Loss: Proposal of Vena Cava Half-Clamp with Trendelenburg Posture to Control Hepatic Venous Bleeding during Hepatectomy

Introduction: Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy to understand the mechanism of hepatic venous bleeding. Method: We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n=18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. Result: The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p<0.05). The parameters associated with an increased BLSW (>13.5 mL/kg) were tumour size (>4 cm), prothrombin activity (<87%), CVP (>7 mmHg), area of suprahepatic IVC (<360 mm2), IVC-RA gap (>28 mm), longitudinal angle of IVC (<160°), and axial angle of the MHV (<55°). Multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.3, p<0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. Although IVC-PC led to a decrease in systolic arterial pressure and difficult to control systemic circulation in many cases, the combined Trenderenburg posture could solve this problem. Conclusions: The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy. Further, in the case of increased IVC gap and hepatic venous bleeding is difficult, our proposal combined procedure is feasible、easy, safe and useful.

The Absorption, Distribution, and Excretion of 18 Elements of Tibetan Medicine Qishiwei Zhenzhu Pills in Rats with Cerebral Ischemia.

The aim of this study is to determine 18 elements in Tibetan medicine Qishiwei Zhenzhu pills (QSW) and their absorption, distribution, and excretion in rats with cerebral ischemia. Microwave digestion and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine 18 elements of QSW in simulated gastrointestinal (GI) juice. Rats were given QSW (66.68 mg/kg) followed by middle cerebral artery occlusion (MCAO). Sham rats received saline and were not subjected to MCAO. ICP-MS was applied to determine the content of 18 elements in hepatic venous blood, abdominal aortic blood, brain, liver, kidney, hair, urine, and feces 24 h after MCAO. In vitro results showed that the extraction rate of Mn, Cu, Sr, Pb, Au, and Hg of QSW in gastric juice (1 h) was higher than that in water, and the contents of Cu, Au, Sr, and As were higher in intestinal juice (4 h) than in water. In vivo results showed that the contents of elements in the blood were quite low, and QSW increased Ni, Cr, Sr, Co, and V in artery blood and decreased V in venous blood. Elements in the tissues were also low, and QSW increased brain Li but decreased Cr and Cd; QSW increased kidney Ag and Cs and liver Mn but decreased liver Ni. QSW increased urinary excretion of Li, Sr, Hg, Cs, and V; QSW increased Hg content in hair but decreased Ni. Stool is the main excretion pathway of the elements in QSW, with Ba, Mn, Sr, Cd, V, Cu, Cs, Li, Pb, Ag, Hg, Cr, As, and Co the highest. In summary, this study examined the distribution of 18 elements in QSW-treated MCAO rats. The accumulation of these elements in blood and tissues was extremely low, and the majority was excreted in feces within 24 h, highlighting the importance of the gut-microbiota-brain axis in QSW-mediated brain protection.

Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience

Simple SummaryPercutaneous hepatic perfusion (PHP) with melphalan is an innovative technique that facilitates the delivery of high-dose chemotherapy to hepatic tumors while limiting systemic toxicity. Patients with uveal melanoma often initially develop hepatic metastases, which are responsive to melphalan; thus, they are particularly eligible candidates for PHP. Additionally, effective systemic therapies for metastatic uveal melanoma are still lacking; hence, further insight into liver-directed methods such as PHP is crucial. The aim of this retrospective two-center study was to pool the data of patients with liver-dominant metastatic uveal melanoma treated with PHP and analyze peri-interventional complications, response, and survival.Percutaneous hepatic perfusion (PHP) delivers high-dose melphalan to the liver while minimizing systemic toxicity via filtration of the venous hepatic blood. This two-center study aimed to examine the safety, response to therapy, and survival of patients with hepatic-dominant metastatic uveal melanoma (UM) treated with PHP. A total of 66 patients with liver-dominant metastasized uveal melanoma, treated with 145 PHP between April 2014 and May 2020, were retrospectively analyzed with regard to adverse events (AEs; CTCAE v5.0), response (overall response rate (ORR)), and disease control rate (DCR) according to RECIST1.1, as well as progression-free and overall survival (PFS and OS). With an ORR of 59% and a DCR of 93.4%, the response was encouraging. After initial PHP, median hepatic PFS was 12.4 (confidence interval (CI) 4–18.4) months and median OS was 18.4 (CI 7–24.6) months. Hematologic toxicity was the most frequent AE (grade 3 or 4 thrombocytopenia after 24.8% of the procedures); less frequent was grade 3 or 4 hepatic toxicity (increased aspartate transaminase (AST) and alanine transaminase (ALT) after 7.6% and 6.9% of the interventions, respectively). Cardiovascular events included four cases of ischemic stroke (2.8%) and one patient with central pulmonary embolism (0.7%). In conclusion, PHP is a safe and effective salvage treatment for liver-dominant metastatic uveal melanoma. Serious AEs—though rare—demand careful patient selection.

Correlation between Hepatic Vein Wave form Changes on Doppler Ultrasound and the Severity of Diseases in Cirrhotic Patients

Background: Cirrhosis is a common problem and is a leading cause of chronic liver disease. Early diagnosis with assessment of severity of diseases may help prevent the associated complications and patients’ sufferings. Now a days Hepatic venous Doppler can be a tool for diagnosis of cirrhosis and to assess correlation between waveform changes and severity of diseases. Objective: The purposes of this study was to determine the significance of hepatic vein waveform changes on doppler ultrasound in cirrhotic patients and to correlate with liver dysfunction. Materials and methods: This study was carried out in the department of Radiology and Imaging of Enam Medical College and Hospital during January 2017 to May 2018. Doppler waveforms were obtained from right hepatic vein in all the cases and classified as triphasic, biphasic and monophasic. Waveform comparisons were made among patients with differing grades of cirrhosis. Child- Pugh class was used to assess severity of cirrhosis. Doppler sonography was done in 80 patients suspecting of having liver cirrhosis. Data on clinical findings, B mode sonographic findings and hepatic vein doppler ultrasound findings were collected and documented in structured forms. Analysis was done using SPSS - 20. Results: Total of 80 patients who met the inclusion criteria are included in the study with mean age of 45.37±7.64 (range 25-75) years. Among these 57 (71%) were males while 23(29%) were females. On the basis of hepatic function 25 (31%) patients presented in Child-Pugh Class A, 31(39%) with Class B and 24(30%) patients had Class C. Hepatic venous waveform was triphasic in 22 (27.5%), biphasic in 28(35%), and monophasic in 30 (37.5%) cases. Our study revealed 88% (21) of Child- Pugh Class C, 23% (7) of Class B and 8% (2) of class A patients had monophasic HV waveform. The hepatic venous waveform progressively changed from triphasic to biphasic to monophasic with advancing grade of cirrhosis. The relationship of these waveforms change had significant relation with hepatic dysfunction (p &lt; 0.022). Conclusion: Hepatic vein wave form changes reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of severity of liver cirrhosis. Thus, alteration in hepatic venous blood flow pattern on doppler ultrasound can be a useful noninvasive tool for evaluating diseases severity in patients with cirrhosis. J MEDICINE 2021; 22: 100-106

Hepatic blood volume is decreased in patients with cirrhosis and does not decrease further after a meal like in healthy persons

Background & Aims The aim was to measure fractional hepatic blood volume (HBV) and hepatic blood flow (HBF) before and after a meal in patients with cirrhosis (n = 7) and healthy persons (n = 6). Methods Catheters were placed in a radial artery and a hepatic vein for blood sampling and a peripheral vein for indocyanine green (ICG) infusion. A 6-min positron emission tomography (PET) liver scan was performed after inhalation of 1000 MBq 15O-CO and repeated after ingestion of a standard meal. HBV was calculated as the 15O-CO concentration in liver tissue (PET) divided by that in arterial blood. HBF was calculated from ICG infusion rate and arterial and hepatic venous blood concentrations according to Fick’s principle. Results Mean fasting HBV was 14 mL blood/100 mL liver tissue in patients with cirrhosis and 21 mL blood/100 mL liver tissue in healthy subjects (p < .01). Mean HBV did not change postprandially in patients with cirrhosis (13 mL blood/100 mL liver tissue) but decreased in healthy subjects (17 mL blood/100 mL liver tissue; p = .02). Mean fasting HBF was 1.5 L blood/min in patients with cirrhosis and 1.1 L blood/min in healthy subjects and increased in both groups of subjects to 1.8 L blood/min. Conclusions Fasting HBV was lower in patients with cirrhosis and did not decrease postprandially as it did in the healthy controls although the HBF increased equally. Patients with cirrhosis thus have a disturbed hemodynamic response to normo-physiological changes such as a meal.

Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication

Background & AimsIn experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication.MethodsWe studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 min. Hepatic and systemic venous blood was sampled simultaneously at 3 time points: baseline, 60, and 180 min after alcohol intervention. Liver biopsies were sampled 240 min after alcohol intervention. We used ultra-high performance liquid chromatography mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples.ResultsAfter alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased, while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, whereas LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared with systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD.ConclusionsAlcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD.Clinical Trials RegistrationThe study is registered at Clinicaltrials.gov (NCT03018990).Lay summaryWe report that alcohol induces hepatic extraction of free unsaturated fatty acids and lysophosphatidylcholines, hepatotoxic lipids which have not been previously associated with alcohol-induced liver injury. We also found that individuals with non-alcoholic fatty liver disease have reduced lipid turnover during alcohol intoxication when compared with people with alcohol-related fatty liver disease. This may explain why alcohol is particularly more harmful in people with non-alcoholic fatty liver and why elevated BMI and alcohol have a synergistic effect on the risk of liver-related death.

Relationship between hepatic venous anatomy and hepatic venous blood loss during hepatectomy.

Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy. We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5mL/kg) were tumor size (> 4cm), prothrombin activity (< 87%), CVP (> 7mmHg), area of suprahepatic IVC (< 360mm2), IVC-RA gap (> 28mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases. The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy.

Bile Salt and FGF19 Signaling in the Early Phase of Human Liver Regeneration.

The involvement of bile salt–fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt–FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous‐arterial differences (ΔVA), and determined hepatic transcript levels on two intra‐operative time points: before (< 1 hour) and immediately after (> 2‐3 hours) liver resection (i.e., following surgery). Postoperative bile salt and FGF19 levels were assessed on days 1, 2, and 3. LR was studied by computed tomography (CT)–liver volumetry. Following surgery, the liver, arterial, and portal bile salt levels were elevated (P < 0.05). Furthermore, an increased amount of bile salts was released in portal blood and extracted by the remnant liver (P < 0.05). Postoperatively, bile salt levels were elevated from day 1 onward (P < 0.001). For FGF19, intra‐operative or postoperative changes of ΔVA or plasma levels were not observed. The bile salt–homeostatic regulator farnesoid X receptor (FXR) was markedly up‐regulated following surgery (P < 0.001). Cell‐cycle re‐entry priming factors (interleukin 6 [IL‐6], signal transducer and activator of transcription 3 [STAT3], and cJUN) were up‐regulated following surgery and were positively correlated with FXR expression (P < 0.05). Postoperative hyperbilirubinemia was preceded by postsurgery low FXR and high Na+/Taurocholate cotransporting polypeptide (NTCP) expression in the remnant liver coupled with higher liver bile salt content (P < 0.05). Finally, bile salt levels on postoperative day 1 were an independent predictor of LR (P < 0.05). Conclusion: Systemic, portal, and liver bile salt levels are rapidly elevated after liver resection. Postoperative bile salts were positively associated with liver volume gain. In the studied time frame, FGF19 levels remained unaltered, suggesting that FGF19 plays a minor role in human LR. These findings indicate a more relevant role of bile salts in human LR.