Portacaval Shunt Research Articles

Antioxidant defense in the rat brain cortex, cerebellum, hippocampus, and striatum and its alterations during portacaval shunting

Portacaval anastomoses spontaneously appear during liver insufficiency and lead to chronic hyperammonemia and hepatic encephalopathy. Ammonium induces oxidative stress in the brain. Here, we compared the state of the antioxidant system in different rat brain areas and studied the manner in which it is affected by portacaval shunting. At 4 weeks after the surgical operation, we measured the activities of catalase, Cu,Zn-superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione transferase in cytoplasm and content of oxidized proteins in mitochondria of the neocortex, cerebellum, hippocampus, and striatum. All four brain regions differed according to the ammonium content and activity of each antioxidant enzyme. The activity of glutathione peroxidase decreased as compared to the control only in the cerebellum and striatum of animals with portacaval shunt. After portacaval shunting, the activities of catalase, Cu,Zn-superoxide dismutase, glutathione peroxidase, and glutathione reductase did not differ from the control in all the brain regions we studied. An inverse correlation between the content of oxidized proteins and activity of glutathione transferase suggests that the diminished activity of glutathione peroxidase in the cerebellum and striatum, but not other antioxidant enzymes and other brain regions, may play a role in the pathogenesis of hepatic encephalopathy.

Congenital Portosystemic Shunts in Children

To propose an anatomical classification of congenital portosystemic shunts (CPSs) correlating with conservative surgery. CPSs entail a risk of life-threatening complications because of poor portal inflow, which may be prevented or cured by their closure. Current classifications based on portal origin of the shunt are not helpful for planning conservative surgery. Twenty-three patients who underwent at least 1 surgical procedure to close the CPSs were included in this retrospective study (1997-2012). We designed a classification according to the ending of the shunt in the caval system. We analyzed the results and outcomes of surgery according to this classification. Two patients had an extrahepatic portosystemic shunt, 17 had a portacaval shunt [subdivided in 5 end-to-side-like portal-caval, 7 side-to-side-like portal-caval, and 5 H-shaped (H-type portal-caval)], 2 had portal-to-hepatic vein shunts (portohepatic), and 2 had a persistent ductus venosus. All extrahepatic portosystemic shunts, H-type portal-caval, portohepatic, and patent ductus venosus patients had a successful 1-stage ligation. All 5 end-to-side-like portal-caval patients had a threadlike intrahepatic portal venous system; a 2-stage complete closure was successfully achieved for 4 and a partial closure for 1. The first 2 side-to-side-like portal-caval patients had a successful 2-stage closure whereas the 5 others had a 1-stage longitudinal caval partition. All patients are alive and none needed a liver transplantation. Our classification correlates the anatomy of CPSs and the surgical strategy: outcomes are good provided end-to-side-like portal-caval shunts patients have a 2-stage closure, side-to-side portal-caval shunts patients have a 1-stage caval partition, and the others have a 1-stage ligation.

Liver resection using total vascular exclusion of the liver preserving the caval flow, in situ hypothermic portal perfusion and temporary porta-caval shunt: a new technique for central tumors.

Standard total vascular exclusion (TVE) of the liver is indicated for resection of tumors involving or adjacent to the vena cava and/or the confluence of the hepatic veins. The duration of liver ischemia can be prolonged by combined portal hypothermic perfusion of the liver (in or ex situ). The use of a venovenous bypass (VVB) during standard TVE maintains stable hemodynamics as well as optimal renal and splanchnic venous drainage. When the hepatic veins can be controlled, TVE preserving the caval flow negates the need for VVB. However this technique remains limited in duration as it is performed under warm ischemia (so-called normothermia) of the liver. To prolong the ischemia time, we have designed a modification of TVE with preservation of the caval flow including the use of temporary porta-caval shunt (PCS) and hypothermic perfusion of the liver. We describe here the first two cases of this new technique. Two patients underwent left hepatectomy extended to segments 5 and 8 (also called extended left hepatectomy) for large centrally located tumors. TVE lasted seventy-two and seventy-nine minutes, respectively. The postoperative course was uneventful and both patients were discharged on day ten and day twenty-five respectively. Both are alive without recurrence at ten and seven months following surgery. Provided the roots of the hepatic veins can be controlled, this technique combines the advantages of standard TVE with in situ hypothermic perfusion and VVB and obviates the need and the subsequent risks of the latter.

Hepatocyte Transplants Improve Liver Function and Encephalopathy in Portacaval Shunted Rats

Rats with portacaval shunt (PCS) are useful experimental models of human hepatic encephalopathy in chronic liver dysfunction. We have previously shown that PCS modifies amine neurotransmitter systems in the CNS and increases voluntary alcohol intake by rats. Hepatocyte transplantation, used in acute liver failure, has recently also been applied to chronic liver diseases, which prompted us to investigate whether the altered brain amine system and the drinking behavior in long-term shunted rats could be normalized by hepatocyte transplants. Hepatocytes, isolated from syngeneic donors by collagenase digestion, were injected (3 × 10(6) cells/rat) into the pancreatic tail region, 6 months after PCS. Hepatic function was evaluated by measuring urine urea and plasma L-histidine concentrations. A free choice test with two bottles (tap water and 10% ethyl alcohol) was performed for 3 days to assess the rats' preference for alcohol. The rats were euthanized 2 months posttransplantation. Brain histamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured by radioenzymatic assay and by HPLC-EC, respectively, N-tele-methylhistamine by GC/MS while MAOA and MAOB activities by isotopic procedures. Portacaval shunt rats with hepatocyte transplants gave more urea than before transplantation, with lower plasma L-His levels and higher body weight versus the PCS counterparts. Also, those rats consumed less alcohol. The CNS amines and 5-HIAA concentrations, as well as MAO-B activity, being abnormally high in untreated PCS rats, significantly reduced after PCS hepatocyte treatment. The results support the therapeutic values of hepatocyte transplants in chronic liver diseases and the temporary character of PCS-exerted CNS dysfunctions.

Educational Exhibit Abstract No. 429 - Endovascular management of uterine arteriovenous malformations: causes, clinical presentation, technique and outcomes

No. 430 Comparison of procedure cost of various percutaneous tumor ablation modalities: microwave ablation, radiofrequency ablation, cryoablation, and irreversible electroporation S. Astani, M.L. Brown, T.M. Getzen, K. Steusloff; Radiology, Henry Ford Hospital, Detroit, MI Purpose: Microwave ablation, radiofrequency ablation, cryoablation, and irreversible electroporation (Nanoknife ablation) are four percutaneous ablation modalities commonly employed to treat tumors. Cost of similarly effective procedures can be an important factor in choosing a treatment option. There is paucity of data regarding the cost of aforementioned ablation modalities. In particular, no prior study has directly compared the cost of these procedures. We compare the procedure cost of treating the same lesion with each of the 4 modalities. Materials and Methods: An interactive model was created for each ablation modality, estimating the cost of treating a tumor based on the number of probes required, which is estimated by the tumor size. Total cost of treating a 3 cm kidney lesion with each modality was separately calculated by mapping out the operation process, material and equipment required as well as time and contribution of involved personnel.In order to validate the cost modules, 62 cases of various percutaneous ablations performed by interventional radiology treating a variety of lesions from July 2010 to March 2012 were identified retrospectively. Cost of each procedure was determined and then compared with the estimated cost based on the modules developed. Results: The cost of treating a 3 cm kidney lesion is $8,123 for microwave ablation, $8,289 for radiofrequency ablation, $10,103 for cryoablation, and $12,984 for irreversible electroporation. There was a strongly positive and statistically significant relationship between estimated cost based on the cost modules and actual cost for all procedures combined, microwave ablations, radiofrequency ablations, cryoablations, and irreversible electroporations. Conclusion: Number of required probes is the most variable and dominant factor in determining the cost of an ablation procedure. In average, cryoablation requires a greater number of probes than microwave or radiofrequency ablations, and is therefore more expensive. Irreversible electroporation requires more ablation probes than cryoablation for the same lesion, which makes it the most expensive procedure between the four ablation modalities. Educational Exhibit Abstract No. 431 Treating complex vascular anomalies with novel techniques D.J. Aria, S. Vatsky, R. Kaye, C. Schaefer, R.B. Towbin; Phoenix Children0s, Phoenix, AZ Learning Objectives: To highlight the use of a minimally invasive novel technique for treatment of a large, symptomatic portacaval shunt.To offer a less costly and time-consuming alternative to traditional surgery/intravascular coil embolization. Background: An 8 year-old girl with a complex medical history including trisomy 21, multiple cardiac anomalies, and chronic anemia of mixed etiology, presented with gastrointestinal bleeding. Over the preceding year, she had become cyanotic and on physical examination, digital clubbing was noted. Laboratory evaluation revealed elevated serum ammonia levels. Abdominal ultrasound demonstrated a congenital portacaval shunt. Clinical Findings/Procedure Details: Due to the large size of the shunt, traditional embolization agents such as coils could not safely be utilized. Although not generally used for this purpose, the decision was made to occlude the fistula with a 14mm Amplatzer ASD occlusion [clamshell] device. The Amplatzer device was deployed at the inferior vena cava and portal vein communication without immediate complication. The patient’s post-operative course was uneventful and the patient was discharged on post-operative day #2. Follow-up visits demonstrated resolution of the clinical signs and symptoms and imaging demonstrated closure of the shunt. Conclusion and/or Teaching Points: This experience highlights the use of a novel technique for treatment of a large, symptomatic portacaval shunt. Educational Exhibit Abstract No. 432 Patient safety checklist in interventional radiology: are they being used and do they work? S. Byott, A. Craig; NHS, Manchester, United Kingdom JVIR ’ Posters and Exhibits S187

Educational Exhibit Abstract No. 431 - Treating complex vascular anomalies with novel techniques

To highlight the use of a minimally invasive novel technique for treatment of a large, symptomatic portacaval shunt. To offer a less costly and time-consuming alternative to traditional surgery/intravascular coil embolization. An 8 year-old girl with a complex medical history including trisomy 21, multiple cardiac anomalies, and chronic anemia of mixed etiology, presented with gastrointestinal bleeding. Over the preceding year, she had become cyanotic and on physical examination, digital clubbing was noted. Laboratory evaluation revealed elevated serum ammonia levels. Abdominal ultrasound demonstrated a congenital portacaval shunt. Due to the large size of the shunt, traditional embolization agents such as coils could not safely be utilized. Although not generally used for this purpose, the decision was made to occlude the fistula with a 14-mm Amplatzer ASD occlusion [clamshell] device. The Amplatzer device was deployed at the inferior vena cava and portal vein communication without immediate complication. The patient’s post-operative course was uneventful and the patient was discharged on post-operative day #2. Follow-up visits demonstrated resolution of the clinical signs and symptoms and imaging demonstrated closure of the shunt. This experience highlights the use of a novel technique for treatment of a large, symptomatic portacaval shunt.

Fifty-three Years’ Experience With Randomized Clinical Trials of Emergency Portacaval Shunt for Bleeding Esophageal Varices in Cirrhosis

Emergency treatment of bleeding esophageal varices (BEV) consists mainly of endoscopic and pharmacologic measures, with transjugular intrahepatic portal-systemic shunt (TIPS) performed when bleeding is not controlled. Surgical shunt has been relegated to salvage. At the University of California, San Diego, Medical Center, our group has conducted 10 studies of emergency portacaval shunt (EPCS) during 46 years. To describe 2 randomized clinical trials (RCTs) conducted from 1988 to 2011 in unselected consecutive patients who received emergency treatment for BEV. In RCT No. 1, a total of 211 unselected consecutive patients with cirrhosis and acute BEV were randomized to emergency endoscopic sclerotherapy (EEST) (n=106) or EPCS (n=105). In RCT No. 2, a total of 154 unselected consecutive patients with cirrhosis and acute BEV were randomized to TIPS (n=78) or EPCS (n=76). Diagnostic workup was completed within 6 hours of initial contact, and primary treatment was initiated within 8 to 12 hours. Regular follow-up for up to 10 years was accomplished in 100% of the patients. In RCT No. 1, EEST or EPCS; in RCT No. 2, TIPS or EPCS. The 2 groups were compared with regard to survival, control of bleeding, portal-systemic encephalopathy, and direct cost of care. RESULTS Distribution in Child risk classes was almost identical. One-third of patients were in Child class C. Permanent control of bleeding was achieved by EEST in only 20% of the patients and by TIPS in only 22%. In contrast, EPCS permanently controlled bleeding in 97% and 100% of the patients in RCT No. 2 and RCT No. 1, respectively (P<.001). Survival was significantly greater following EPCS than after EEST and TIPS (P<.001). Median survival was more than 10 years following EPCS compared with 1.99 years after TIPS. Occlusion of TIPS was demonstrated in 84% of the patients, 63% of whom underwent TIPS revision, which failed in 80% of the cases. Recurrent portal-systemic encephalopathy developed in 35% of the patients who underwent EEST and 61% of those who received TIPS. In contrast, portal-systemic encephalopathy occurred in 15% of the patients who received EPCS in RCT No. 1 and 21% of those in RCT No. 2. Direct costs of care were 5 to 7 times greater in the EEST ($168100) and TIPS ($264800) groups than in the EPCS ($39000) group (P<.001). Emergency portacaval shunt permanently stopped variceal bleeding, almost never became occluded, accomplished 5 times the long-term survival than EEST or TIPS, and was much less costly than EEST or TIPS. The widespread practice of using EPCS mainly as salvage for failure of endoscopic therapy or TIPS is not supported by the definitive results of these long-term RCTs in unselected patients with cirrhosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00690027 and NCT00734227.

Differences between cerebellum and hippocampus in antioxidant system

The effect of portacaval shunting on the antioxidant status of the cerebellum and hippocampus was studied in rats using standard methods of enzymatic analysis. Endogenous ammonia levels and activities of eight antioxidant enzymes were shown to be unequal in two brain regions and to respond differently upon portal-systemic shunt surgery.

Differences of antioxidant systems in the cerebellum and hippocampus

The effect of portacaval shunting on the antioxidant status of the cerebellum and hippocampus has been studied in rats using standard methods of enzymatic analysis. Endogenous ammonia levels and activities of eight antioxidant enzymes were shown to be unequal in these two brain regions and to respond differently to intrahepatic portosystemic shunt surgery.

Rats with minimal hepatic encephalopathy due to portacaval shunt show differential increase of translocator protein (18 kDa) binding in different brain areas, which is not affected by chronic MAP-kinase p38 inhibition

Neuroinflammation plays a main role in neurological deficits in rats with minimal hepatic encephalopathy (MHE) due to portacaval shunt (PCS). Treating PCS rats with SB239063, an inhibitor of MAP-kinase-p38, reduces microglial activation and brain inflammatory markers and restores cognitive and motor function. The translocator protein-(18-kDa) (TSPO) is considered a biomarker of neuroinflammation. TSPO is increased in brain of PCS rats and of cirrhotic patients that died in hepatic coma. Rats with MHE show strong microglial activation in cerebellum and milder in other areas when assessed by MHC-II immunohistochemistry. This work aims were assessing: 1) whether binding of TSPO ligands is selectively increased in cerebellum in PCS rats; 2) whether treatment with SB239063 reduces binding of TSPO ligands in PCS rats; 3) which cell type (microglia, astrocytes) increases TSPO expression. Quantitative autoradiography was used to assess TSPO-selective (3)H-(R)-PK11195 binding to different brain areas. TSPO expression increased differentially in PCS rats, reaching mild expression in striatum or thalamus and very high levels in cerebellum. TSPO was expressed in astrocytes and microglia. Treatment with SB239063 did not reduces (3)[H]-PK11195 binding in PCS rats. SB239063 reduces microglial activation and levels of inflammatory markers, but not binding of TSPO ligands. This indicates that SB239063-induced neuroinflammation reduction in PCS rats is not mediated by effects on TSPO. Also, enhanced TSPO expression is not always associated with cognitive or motor deficits. If enhanced TSPO expression plays a role in mechanisms leading to neurological alterations in MHE, SB239063 would interfere these mechanisms at a later step.

Traumatic Portacaval Shunt: A Case Report and Literature Review

Computed tomography (CT) evaluation of the acute polytrauma patient has become well established as a mainstay of ER triage in hemodynamically stable patients. The radiologist plays a pivotal role in directing management by identifying and appropriately categorizing the severity of a patient's injuries. High-grade liver injuries have undergone an increasing trend of nonoperative management over the last several decades, with concurrent decrease in mortality. However, we present a case of a patient with a grade V liver laceration, in whom a rare portacaval shunt was also present. In the setting of this rare injury, the radiologist will likely be the first person to recognize and categorize a severe complication, which may indicate the need for a fundamental change in patient management.

Reduced clearance of proteins labeled with diisopropylfluorophosphate in portacaval-shunted rats

Portacaval shunting is a model for hepatic encephalopathy that causes chronic hyperammonemia, disruption of metabolic, signaling, and neurotransmitter systems, and progressive morphological changes. Exposure of cultured cells to ammonia raises intralysosomal pH and inhibits proteolysis, and the present study tested the hypothesis that proteolytic capacity is diminished in portacaval-shunted rats. Proteins were labeled in vivo with tracer doses of diisopropylfluorophosphate (DFP) and clearance of label was assayed. This approach labeled proteins independent of protein synthesis, which is reported to be altered in shunted rats, and avoided complications arising from re-utilization of labeled amino acids that causes underestimation of degradation rate. Characterization of DFP labeling showed that protein labeling was fast, about 50% of the label was released during a 24 h interval, labeling by DFP metabolites was negligible, inhibition of brain acetylcholinesterase was not detectable, and labeling by [(3)H]- and [(14)C]DFP was equivalent. To assay degradative capacity, proteins were first labeled with [(3)H]DFP, followed by labeling with [(14)C]DFP that was given 24 or 72 h later. The (3)H/(14)C ratio in each animal was used as a relative measure of removal of (3)H-labeled proteins. (3)H/(14)C ratios were generally significantly higher in portacaval-shunted rats than in controls, consistent with reduced proteolytic capacity. Assays of amino acid incorporation into brain protein generally replicated literature reports, supporting the conclusion that protein synthesis unlikely to be markedly inhibited and amino acid recycling influences calculated protein synthesis rates in shunted rats. Therapeutic strategies to reduce ammonia level would help normalize lysosomal functions and protein and lipid turnover.

Portacaval Shunt Established in Six Dogs Using Magnetic Compression Technique

Background and AimsInstalling the transjugular intrahepatic portosystemic shunt for portal hypertension is relatively safe, but complications are still high. To explore a new method of portacaval shunt, the magnetic compression technique was introduced into the shunting procedure.MethodsA portal-inferior vena cava shunt was performed on 6 male mongrel dogs by two hemocompatible Nd-Fe-B permanent magnets, parent and daughter. The parent magnet was applied to the inferior vena cava guided by a catheter through the femoral vein. The daughter magnet was moved to the anastomosis position on the portal vein with a balloon catheter through the splenic vein. After the daughter magnet reached the target position, the two magnets acted to compress the vessel wall and hold it in place. Five to 7 days later, under X-ray guidance, the magnets were detached from the vessel wall with a rosch-uchida transjugular liver access set. One month later, histological analysis and portal venography were performed.Results5-7 days after the first surgery, a mild intimal hyperplasia in the portal vein and the inferior vena cava, and continuity of the vascular adventitia from the portal vein to the inferior vena cava as observed. During the second surgery, the contrast media could be observed flowing from the portal vein into the inferior vena cava. Portal venography revealed that the portosystemic shunt was still present one month after the second surgery.ConclusionsMagnamosis via a device of novel design was successfully used to establish a portacaval shunt in dogs.

Exhaled breath analysis with electronic nose technology for detection of acute liver failure in rats

The aim of this study was to assess the classification accuracy of an e-Nose in detecting acute liver failure (ALF) in rats. Exhaled breath from 14 rats was repeatedly sampled by e-Nose (8 sensors) and an additional external CO2 sensor at three stages: healthy period; portacaval shunt; and during the development of ALF due to surgically induced complete liver ischemia. We performed principal component analysis (PCA) on the (grouped) sensor data in each stage and the classification accuracy of the first two principal components was assessed by the leave-one-out approach. In addition we performed gas chromatography–mass spectrometry (GC–MS) analysis of the exhaled breath from three rats.The first and second principal components from the PCA analysis of e-Nose data accounted for more than 95% variance in the data. Measurements in the ALF stage were contrasted with the measurements in the control stage. Leave-one-out validation showed classification accuracy of 96%. This accuracy was reached after 3h of ALF development, and was reached already after 2h when data of an external CO2 sensor were also included. GC–MS identified 2-butanol, 2-butanone, 2-pentanone and 1-propanol to be possibly elevated in the ALF stage.This is the first study to demonstrate that ALF in rats can be detected by e-Nose data analysis of the exhaled breath. Confirmation of these results in humans will be an important step forward in the non-invasive diagnosis of ALF.

A modified microsurgical model for end-to-side selective portacaval shunt in the rat: intraoperative microcirculatory investigations

To investigate the intraoperative microcirculatory changes of the affected organs (small bowel, liver and kidney) during the making of a modified selective portacaval (PC) shunt. On ten anaesthetized Sprague-Dawley rats the selective end-to-side mesocaval anastomosis was performed, where only the rostral mesenteric vein is utilized and the portal vein with the splenic vein are left intact. Morphometric and microcirculatory investigations using a LDF device determining flux units (BFU) were carried out. After completing the shunts the microcirculatory flux values did not recover in the same manner on the surface of the small intestine, the liver or the kidney. BFU values showed deterioration in the small intestine and in the liver (p<0.001). During the reperfusion the BFU values improved, but not in the same manner. The small intestine values left behind the kidney and liver data. Technically, the advantages of the models include the selective characteristic, the mesocaval localization and the relatively easy access to those vessels. However, its major disadvantage is the time needed for positioning the vessels without coiling or definitive stretching. Intraoperative LDF may provide useful data on the microcirculatory affection of the organs suffering from hypoperfusion or ischemia during creating the shunts.

Cerebral oedema is not responsible for motor or cognitive deficits in rats with hepatic encephalopathy

Low-grade cytotoxic oedema is considered a main contributor to the neurological (motor and cognitive) alterations in patients with hepatic encephalopathy (HE). This assumption is mainly based on studies with cultured astrocytes treated with very large ammonia concentrations or with animal models of acute liver failure with strong HE. However, the possible contribution of cerebral oedema (vasogenic or cytotoxic) to cognitive or motor alterations in chronic mild HE has not been demonstrated. The aim of this work was to assess whether cerebral oedema contributes to cognitive and/or motor alterations in rats with chronic mild HE. Motor activity and coordination and different types of learning and memory were assessed in rats with porta-caval shunts (PCS). Brain oedema was assessed by gravimetry in cerebellum and cortex and apparent diffusion coefficient (ADC) by magnetic resonance in 16 areas. Four weeks after surgery, PCS rats show reduced motor activity and coordination, impaired ability to learn a conditional discrimination task in the Y maze and reduced spatial memory in the Morris water maze. PCS rats did not show increased brain water content at 4 or 10 weeks or changes in ADC at 4 weeks. At 10 weeks, increased ADC in some areas is compatible with vasogenic but not cytotoxic oedema. Cerebral oedema is not involved in motor and cognitive alterations in rats (and likely in humans) with mild HE. Proper understanding of the mechanisms responsible for the neurological alterations in HE is necessary to design efficient treatments.

Evaluation of the Hepa Wash®treatment in pigs with acute liver failure

BackgroundMortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF.MethodsIn the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h.ResultsAll animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed.ConclusionsHepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Liver Transplantation during Fifty-Three Years’ Experience with Randomized Controlled Trials of Emergency Portacaval Shunt for Bleeding Esophageal Varices in Cirrhosis

Background: Currently, emergency treatment of Bleeding Esophageal Varices (BEV) consists mainly of endoscopic and pharmacologic measures, with use of TIPS when bleeding is not controlled. Surgical shunt has been relegated to salvage of survivors of failed endoscopic, pharmacologic, and TIPS treatment. We have conducted 10 prospective studies of Emergency Porta Caval Shunt (EPCS) during 46 years. BEV in cirrhosis has been considered an indication for Liver Transplantation (LT) by some respected LT programs. This important issue was examined in our two recent Randomized Controlled Trials (RCTs) in 365 unselected, consecutive patients with acute BEV conducted from 1988 to 2011. Study design: In RCT No. 1, 211 unselected, consecutive cirrhotic patients with acute BEV (“all comers”) were randomized to Emergency Endoscopic Sclerotherapy (EEST) (n=106) or EPCS (n=105). In RCT No. 2, 154 unselected consecutive cirrhotic patients with acute BEV (“all comers”) were randomized to TIPS (n=78) or EPCS (n=76). In each RCT, the two treatment groups were compared with regard to effect on survival, control of bleeding, encephalopathy, and direct cost of care. Diagnostic workup was completed within 6 hr and primary treatment was initiated within 8 to 12 hours. Regular follow-up was accomplished in 100% of patients. In RCT No. 1, 96% of patients underwent more than 10 years of follow-up, or until death. In RCT No. 2, follow-up lasted for 5 to 10 years in 85%, and 3 to 4.5 years in the remainder. Patients were evaluated for LT on admission and at regular intervals thereafter. In addition to the two RCTs, the analysis of LT was supplemented in 1300 unrandomized cirrhotic patients who previously underwent Porta Caval Shunt (PCS) with 100% follow-up. Results: Clinical characteristics of each group were similar at the time of enrollment. The distribution of patients in Child risk classes was almost identical in the two groups in each RCT. Almost one-third of patients in each group were in Child class C. Permanent control of bleeding was achieved by sclerotherapy in only 20% and by TIPS in only 22%. In contrast, EPCS permanently controlled bleeding in 97% to 100% (p<0.001). Sclerotherapy and TIPS patients required twice as many units of blood transfusion as EPCS patients. Survival rate at all time intervals and in all Child classes was significantly greater following EPCS than after sclerotherapy and TIPS (p<0.001). Median survival was over 10 years following EPCS, compared to 1.99 years following TIPS. EPCS remained permanently patent in 97% of patients. In contrast, stenosis or occlusion of TIPS was demonstrated in 84% of patients, 63% of whom underwent TIPS revision, which failed in 80%. Recurrent episodes of encephalopathy developed in 35% of sclerotherapy patients and 61% of TIPS patients. In contrast, encephalopathy occurred in 15% of EPCS patients in RCT No. 1 and 21% of EPCS patients in RCT No. 2. Direct costs of care, measured as charges per year, were 5 to 7 times greater in the sclerotherapy group ($168,100) and TIPS groups ($264,800) than in the EPCS group ($39,000) (p<0.001). Of the 365 randomized patients in the two RCTs, only 23 (6.3%) were ultimately referred for LT, mainly because of progressive liver failure. Of these, only 11 (3%) were approved for LT, and only 8 (2.2%) underwent LT. One- and 5-year LT survival rates were 0.68% and 0, compared to 81% and 73% after EPCS. In the 1300 unrandomized PCS patients, 50 (3.8%) were referred and 19 (1.5%) underwent LT. Five-year survival rate was 53% compared to 72% for all 1300 patients. Conclusions: EPCS was uniformly effective in treatment of BEV, while sclerotherapy and TIPS were disappointing. EPCS permanently stopped variceal bleeding, almost never became occluded, accomplished long-term survival that was more than 5 times survival rate following sclerotherapy or TIPS, and was much less costly than sclerotherapy or TIPS. If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. Neither EST nor TIPS are effective emergency or long-term therapeutic measures.

Prospective analysis of 44 consecutive liver transplants performed at a university hospital

To analyze the intraoperative and immediate postoperative biochemical parameters of patients submitted to orthotopic liver transplantation. Forty four consecutive orthotopic liver transplants performed from October 2009 to December 2010 were analyzed. The patients (38 male and eight female) were divided into two groups: group A, survivors, and group B, non-survivors. Fifty percent of group A patients were Chid-Pugh C, 40% Chid-Pugh B and 10% Chid-Pugh A. In group B, 52% of the patients were Chid-Pugh C, 41% Chid-Pugh B, and 17% Chid-Pugh A. All orthotopic liver transplants were performed by the piggy-back technique without a portacaval shunt in an anhepatic phase. ALT, AST, LDH and lactate levels were determined preoperatively, at five, 60 minutes after arterial revascularization of the graft and 24 and 48 hours after the end of the surgery.( or: after the surgery was finished). There were no preoperative clinical differences (Child and Meld) between the two groups. The times of warm and hypothermal ischemia were similar for both groups (p>0.05). Serum aminotransferases levels at five and 60 minutes after arterial revascularization of the graft were similar (p>0.05) for both groups, as also were lactate levels at the time points studied. There was no significant difference in Δ lactate between groups at any time point studied (p>0.05). No significant difference was observed between groups during the first 24 and 48 hours after surgery (p>0.05). No significant difference in any of the parameters studied was observed between groups. Under the conditions of the present study and considering the parameters evaluated, no direct relationship was detected between the intraoperative situation and the type of evolution of the patients of the two groups studied.

The effect of portacaval anastomosis on the expression of glutamine synthetase and ornithine aminotransferase in perivenous hepatocytes

There is functional zonation of metabolism across the liver acinus, with glutamine synthetase restricted to a narrow band of cells around the terminal hepatic venules. Portacaval anastomosis, where there is a major rerouting of portal blood flow from the portal vein directly to the vena cava bypassing the liver, has been reported to result in a marked decrease in the activity of glutamine synthetase. It is not known whether this represents a loss of perivenous hepatocytes or whether there is a specific loss of glutamine synthetase. To answer this question, we have determined the activity of glutamine synthetase and another enzyme from the perivenous compartment, ornithine aminotransferase, as well as the immunochemical localization of both glutamine synthetase and ornithine aminotransferase in rats with a portacaval shunt. The portacaval shunt caused a marked decrease in glutamine synthetase activity and an increase in ornithine aminotransferase activity. Immunohistochemical analysis showed that the glutamine synthetase and ornithine aminotransferase proteins maintained their location in the perivenous cells. These results indicate that there is no generalized loss of perivenous hepatocytes, but rather, there is a significant alteration in the expression of these proteins and hence metabolism in this cell population.