Presence Of Portosystemic Shunt Research Articles

Comment on "Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts".

We would like to congratulate the authors for publishing this important article on the outcome of utilizing left lobe grafts in their series of living donor liver transplantation (LDLT).1 Their study represents one of the largest series of utilizing left lobe grafts in the West and showed favorable 1-, 3-, and 5-year graft survival of 97%, 94%, and 89% comparable to the right lobe graft survival of 99%, 96%, and 93% (P = 0.97). This contrasts sharply from the European experience of 46 left lobe LDLTs from 4 centers showing a relatively poor 1-year graft survival of 59.4% due to a high rate of small for size syndrome (SFSS) and hepatic artery thrombosis.2 The key to their excellent outcomes was achieved by the use of venous outflow augmentation and liberal use of splenectomy to modulate portal inflow. From their series, 61 of 130 (47%) recipients received left lobe graft. Donor/recipient selection likely played a huge role to their highly favorable outcomes. The Kyoto group previously showed that the overall survival was significantly worse when using left lobe graft compared with right lobe graft in recipients who were considered high risk (at least 2 risk factors of: model for end-stage liver disease [MELD] score > 20; preoperative hospitalization; recent preoperative bacterial infection).3 In contrast, no difference in survival were found between left lobe or right lobe recipient if only 1 risk factor was present. The Kyushu group reported donor age ≥ 48 years, MELD score ≥ 19, and end portal venous pressure ≥ 19 mm Hg as the important factors for the development of SFSS.4 These factors reflect on the poor graft quality from higher donor age, poor clinical status of the recipient and excessive portal flow after reperfusion of the partial graft. To highlight the important of graft selection, the Kyushu group has also devised a scoring system that incorporates factors such as graft size, donor age, MELD score, and the presence of portosystemic shunts, which correlate well with graft survival and can be employed for graft selection.5 Although there is currently no consensus on the selection criteria when comes to choosing left lobe graft, most groups have demonstrated that donor age, and MELD score as crucial deciding factors as mentioned. In fact, the European cohort with poor outcome with left lobe grafts reported MELD score >14 as the most significant factor for the development of SFSS.2 Looking at the Cleveland cohort, it is very clear that this is a highly selected group of donors and recipients when considering for left lobe graft with a donor median age of 36 years (interquartile range, 31–41 years), low median MELD score of 12 (interquartile range, 10, 16), and less severe portal hypertension as evident by the low median splenic volume (611 mL for left lobe graft compared with 918 for right lobe graft). Their left lobe graft experience has been accumulated over 8 years from 2013 to 2020 sharing between the 2 centers ranging from 5 to 17 left lobe grafts per year (mean 7 to 8 per year). This likely represents only a fraction of their overall liver transplant activity and further suggests that the recipients chosen for left lobe graft were highly selected. As regards to the use of inflow modulation such as splenectomy in this series, a group from Tokyo has described in their series of 42 LDLTs using exclusively left lobe graft without the use of any inflow modulation technique with a very good 1-, 3-, and 5-year graft survival rate of 100%, 97%, and 91%, despite 38% of their recipients had graft-to-recipient weight ratio (GRWR) of less than 0.8%.6 Therefore, it is unclear how much contribution to current reported outcomes were related to patient selection or the use of splenectomy, the use of which has been shown to be a protective for graft dysfunction here. Although the reported morbidities with splenectomy were acceptable in this series, with sicker recipients, the added morbidity of splenectomy may become problematic and could lead to worse outcomes. It has been well established that the grafts are considered small for size when the GRWR is less than 0.8% or the standard liver volume is less than 35%.7 This article has also reported the graft outcome when actual size of the graft was smaller than the expected minimum GRWR of 0.6%. While the 5-year graft survival of 88% and only 1 mortality amongst the 9 left lobe recipients is impressive, this is still small numbers, from selected donors and recipients. Until there are more data and replication of this practice in other centers, we feel that the usage of small left lobe grafts remains an option for very few and not a promised land for the many.

Ammonia and the Muscle: An Emerging Point of View on Hepatic Encephalopathy.

In the last years the link between the presence of muscular alterations and hepatic encephalopathy (HE), both minimal and overt, has been deeply studied. The pathophysiological background supporting the relationship between muscle depletion, and HE is characterized by an imbalance between the capacity of muscle in ammonia metabolism and trafficking and the inability of the liver in removing ammonia through urea synthesis due to liver failure and/or the presence of porto-systemic shunts. This review will focus on the clinical burden, the physio pathological mechanisms understanding the liver muscle axis and principles of management of muscular alterations in cirrhosis.

Screening for portopulmonary hypertension using computed tomography-based measurements of the main pulmonary artery and ascending aorta diameters in patients with portal hypertension.

This study aimed to demonstrate the feasibility of identifying candidates of portopulmonary hypertension (PoPH) from general portal hypertension patients based on chest computed tomography (CT) results. One hundred and thirty patients with portal hypertension who had undergone interventional radiology therapies at our hospital between August 2011 and July 2021 were included, and preoperative clinical data were collected. Suspicious PoPH was defined as main pulmonary artery diameter (mPA-D)≥29mm or the ratio of mPA-D to ascending aorta diameter (mPA-D/aAo-D)≥1.0, and probable PoPH as mPA-D≥33mm based on the chest CT. Prevalence of suspicious and probable PoPH was evaluated, and the differences in clinical characteristics of each population were compared. Overall, 29 (22.3%) and 5 (3.8%) patients were categorized as suspicious and probable PoPH, respectively. Univariate analyses revealed that female sex, higher shortest diameter of inferior vena cava, presence of portosystemic shunts ≥5mm, and lower blood urea nitrogen levels were significantly associated with suspicious PoPH (p<0.05). Multivariate analyses identified all four factors as significantly independent determinants of suspicious PoPH (p<0.05). In addition, among the population of suspicious PoPH, there were significant differences in seven parameters, including total bilirubin levels and spleen volume between patients with and without probable PoPH (p<0.05). However, no significant independent indicators of probable PoPH were found. CT-based measurements of mPA-D and mPA-D/aAo-D have the potential to screen patients with suspicious PoPH in clinical practice focused on portal hypertension.

Prevalence and Risk Factors of Minimal Hepatic Encephalopathy in Patients with Compensated Liver Cirrhosis

Background: Minimal hepatic encephalopathy (MHE) is the earliest phase of hepatic encephalopathy. It is associated with increased risk of falls, impaired work and diminished quality of life. Subjects and methods: This study included 302 patients with liver cirrhosis, of which 130 patients had Child A (compensated) liver cirrhosis. All patients were assessed by history taking, clinical examination, routine investigations, serum ammonia level and abdominal ultrasound for porto-systemic shunt (PSS). MHE was diagnosed in 60 patients of compensated liver cirrhosis patients using mini-mental state examination (MMSE) and number connection test A (NCT-A). Results: Our stud showed that Child A patients were 43% of the study group and MHE was present in 46% of compensated liver cirrhosis patients. Our results showed a significant association between lower serum albumin, higher INR, high serum ammonia, presence of PSS in ultrasound examination and MMSE and NCT-A high scores with the development of MHE. MMSE and NCT A showed significantly good performance in diagnosis of MHE. Multiple regression analysis showed that high serum ammonia level (53-61) u/dl, large PSS (> 8 mm in diameter), MMSE score (22-26) and NCT A score (45-56) were the most significant risk factors for MHE. Conclusion: MHE is a major and prevalent manifestation in compensated liver cirrhosis patients. It is associated with significant decrease in work and driving abilities and quality of life. Its major risk factors are high serum ammonia, large PSS and high scores of MMSE and NCT A tests that have a good performance in MHE diagnosis.

P: 53 Extent of Sarcopenia Does Not Correlate With Degree of Minimal Hepatic Encephalopathy in patients on Treatment for Hepatric Encephalopathy

BACKGROUND: Minimal hepatic encephalopathy affects over half of the patients with cirrhosis. It leads to deterioration of quality of life due to cognitive deficit. Both presence of sarcopenia and portosystemic shunts have been implicated in development of minimal hepatic encephalopathy. We retrospectively assessed the significance of sarcopenia and presence of portosystemic shunts in patients with minimal hepatic encephalopathy. METHODS: Patients with cirrhosis of liver attending the liver clinic at University of Padua underwent a detailed elective outpatient assessment for neurocognitive function. This included Psychometric Hepatic Encephalopathy Score (PHES), computer based tests, and EEG. We then selected patients who underwent a computed tomography for any reason within 3 months of the neurocognitive assessment. The degree of sarcopenia and presence of portosystemic shunts was evaluated on the scan. Presence of more than one shunt was accounted and adjusted for appropriately using a physiological approach previously described. RESULTS: A total of 120 patients had a CT scan within 3 months of the neurocognitive assessment. Of these, 100 were found to be suitable for analysis. Mean age of the patients was 59 ± 9.6 yrs and 73% were males. Median Child Pugh score was 8 (IQR 6–10) and MELD was 12 (IQR 10–18). Alcohol and viral etiologies responsible for 40% and 39% cases respectively. Based on Psychometric Hepatic Encephalopathy Score (PHES), 39% had minimal hepatic encephalopathy. Medication details were available for 87 patients, 70% of whom were on some form of treatment of hepatic encephalopathy with lactulose, antibiotics, or probiotics. The degree of cognitive dysfunction (PHES) correlated significantly with education (r = 0.33), shunt size (r = −0.45), and degree of hyperammonemia (r = −0.48), but not with sarcopenia or degree of hepatic dysfunction. Correlation between total effective shunt size and PHES was more pronounced in women (r = −0.68). Upon multivariate analysis, none of these variables predicted PHES. EEG mean dominant frequency correlated significantly with total effective shunt size (r = −0.30), ammonia (r = −0.34), and Child-Pugh score (r = −0.38). None of the parameters significantly correlated with critical flicker frequency. There was no difference in the degree of sarcopenia among patients with and without MHE or history of overt HE. Moreover, degree of sarcopenia did not correlate with PHES, critical flicker frequency, ammonia level, or Child-Pugh score. Effective size of portosystemic shunt was higher in patients with MHE. CONCLUSIONS: Among patients with cirrhosis on anti-encephalopathy treatment, presence of sarcopenia does not correlate with neurocognitive parameters. Presence of large portosystemic shunts correlated with neurocognitive impairment.

The Portosystemic Shunt Syndrome and Role of Shunt Embolization in the Management of Hepatic Encephalopathy

Portosystemic shunting (PSS) is a result of changes in hepatic hemodynamics where portal flow diverts away from the liver due to increased intrahepatic resistance from cirrhosis and is associated with hepatic encephalopathy (HE). Over time, increased PSS may directly lead to worsening liver failure because of severely decreased loss of effective portal inflow towards the liver and result in recurrent or persistent HE. This clinical scenario has been recently defined as “portosystemic shunt syndrome” and has been associated with poor clinical outcomes. The presence of PSS is common in patients with cirrhosis and increased PSS size appears to correlate with recurrent or persistent HE. Recent studies have shown that patients with Model for End-Stage Liver Disease (MELD) score < 11 have demonstrated high clinical benefit in recurrent or persistent HE when treated with shunt embolization. There is a growing literature that demonstrates potential clinical benefit using PSS embolization for selected patients, particularly with MELD under 11, with recurrent or persistent HE. Further investigation into improved risk stratification in order to determine effective treatments is necessary as well as heightened detection of the portosystemic shunt syndrome in its earlier and possibly reversible stages.

Reversible Extrapyramidal Syndrome in a Patient with Splenic Vein Thrombosis without Overt Hepatic Dysfunction

Acquired hepatocerebral degeneration (AHD) is an extrapyramidal syndrome that develops secondary to hepatic dysfunction. It may accompany advanced liver disease and is related to the presence of portosystemic shunts. We describe a 44-year-old woman who presented with bleeding from gastric fundus varices secondary to splenic vein thrombosis and concomitant development of rapidly progressive extrapyramidal symptoms. No overt liver dysfunction was identified. Brain imaging demonstrated damage to the basal ganglia. The splenic artery was embolized with disappearance of the varices. Medical treatment consisted of amantadine and low-dose clonazepam for 6 months. The patient's neurologic symptoms gradually improved with few sequelae, although imaging demonstrated residual basal ganglia damage. This case highlights the need to identify reversible causes of AHD and treat them rapidly in order to halt progressive damage. The general prognosis of patients with AHD remains poor, and flow interruption in portosystemic shunts must always be taken into account. Rapid diagnosis and treatment could ameliorate the poor prognosis.

Endothelial notch signaling is essential to prevent hepatic vascular malformations in mice.

Liver vasculature is crucial for adequate hepatic functions. Global deletion of Notch signaling in mice results in liver vascular pathologies. However, whether Notch in endothelium is essential for hepatic vascular structure and function remains unknown. To uncover the function of endothelial Notch in the liver, we deleted Rbpj, a transcription factor mediating all canonical Notch signaling, or Notch1 from the endothelium of postnatal mice. We investigated the hepatic vascular defects in these mutants. The liver was severely affected within 2 weeks of endothelial deletion of Rbpj from birth. Two-week old mutant mice had enlarged vessels on the liver surface, abnormal vascular architecture, and dilated sinusoids. Vascular casting and fluorosphere passage experiments indicated the presence of porto-systemic shunts. These mutant mice presented with severely necrotic liver parenchyma and significantly larger hypoxic areas, likely resulting from vascular shunts. We also found elevated levels of VEGF receptor 3 together with reduced levels of ephrin-B2, suggesting a possible contribution of these factors to the generation of hepatic vascular abnormalities. Deletion of Rbpj from the adult endothelium also led to dilated sinusoids, vascular shunts, and necrosis, albeit milder than that observed in mice with deletion from birth. Similar to deletion of Rbpj, loss of endothelial Notch1 from birth led to similar hepatic vascular malformations within 2 weeks. Endothelial Notch signaling is essential for the development and maintenance of proper hepatic vascular architecture and function. These findings may elucidate the molecular pathogenesis of hepatic vascular malformation and the safety of therapeutics inhibiting Notch. (Hepatology 2016;64:1302-1316).

Hepatic encephalopathy

Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers.

Graft selection strategy in adult-to-adult living donor liver transplantation: When both hemiliver grafts meet volumetric criteria.

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914-922 2016 AASLD.

Major predictors of portal hypertensive enteropathy in patients with liver cirrhosis

Portal hypertensive enteropathy (PHE) is acknowledged as a source of bleeding, and predicting its presence has become more important. We assessed PHE using capsule endoscopy (CE) and investigated factors that may predict its presence, including portosystemic shunts (PSs). We analyzed data from 134 consecutive patients with liver cirrhosis, from February 2009 to September 2013. All patients had undergone dynamic computed tomography and esophagogastroduodenoscopy before CE examination. The frequencies and types of PHE lesions, and the relationships between the presence of PHE and patients' clinical characteristics were evaluated. The distribution of the lesions was also determined. PHE was found in 91 (68%), erythema in 70 (52%), erosions in 25 (19%), angioectasia in 24 (18%), villous edema in 18 (13%), and varices in 10 (7%) patients. Most lesions were located in the jejunum. The clinical characteristics associated with the presence of PHE were a Child-Pugh grade of B or C (P = 0.0058), and the presence of PSs (P < 0.0001), ascites (P = 0.0017), portal thrombosis (P = 0.016), esophageal varices (P = 0.0017), and portal hypertensive gastropathy (P = 0.0029). The presence of PSs was an independent predictor of PHE (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.27-7.95). Among the shunt types, left gastric vein (OR: 5.31; 95% CI: 1.97-17.0) and splenorenal shunts (OR: 4.26; 95% CI: 1.29-19.4) were independent predictors of PHE. PSs, especially left gastric vein and splenorenal shunts, appear to reliably predict the presence of PHE.

Evaluation of Venous Ammonia Level, Splenic Longitudinal Diameter, Portal Vein and Splenic Vein Diameters as Non-Invasive Indicators for the Presence of Portosystemic Collaterals in Egyptian Cirrhotic Patients

Introduction and Aim of the Work: The identification of cirrhotic patients with esophageal varices or other portosystemic collateral by non-invasive means is appealing in that it could decrease the necessity of endoscopic screening. This study was to evaluate the diagnostic utility of venous ammonia level with other ultrasonographic parameters as non-invasive markers for the presence of portosystemic shunts. Patients and methods: The study included 3 groups of Child Pugh class A and early B patients. Group (A): 25 patients with evidence of both esophageal varices and portosystemic collaterals; group (B) 25 patients with neither evidence of varices nor portosystemic collaterals and group (C): 25 patients with evidence of varices but no collaterals. Measurement of venous ammonia level was done for all patients. Results: serum ammonia level was significantly higher in group A (222.8 ± 54 μg/dL) than that in group B (85 ± 21.1 μg/dL) and group C (148.2 ± 19.6 μg/dL). The cut-off value of serum ammonia level 113 μg/dL was a good predictor for the presence of esophageal varices, while the cut-off value of serum ammonia level at 133 μg/dL was a good predictor for the presence of both esophageal varices and abdominal collaterals. Combination of portal vein diameter > 13mm + splenic vein diameter > 8.9mm + ammonia level > 133 μg/dL gives 100% of sensitivity and 96% of specificity for the prediction of the presence of portosystemic shunts. Conclusion: Determination of serum ammonia level, splenic, portal vein and splenic vein diameters are considered as good predictors for the presence of portosystemic shunts in patients with liver cirrhosis.

Modulation of graft vascular inflow guided by flowmetry and manometry in liver transplantation

Survival of the partial graft after living donor liver transplantation owes much to its tremendous regenerative ability. With excellent venous outflow capacity, a graft within a wide range of graft-to-standard-liver-volume ratios can cope with portal hypertension that is common in liver transplant recipients. However, when the ratio range is exceeded, modulation of graft vascular inflow becomes necessary for graft survival. The interplay between graft-to-standard-liver-volume ratio and portal pressure, in the presence of portosystemic shunt or otherwise, requires individualized modulation of graft portal and arterial inflows. Boosting of portal inflow by shunt ligation can be guided by transonic flowmetry, whereas muting of portal inflow by splenic artery ligation can be monitored by portal electronic manometry. We describe four cases to illustrate the above. One patient had hepatic artery thrombosis resulting from splenic artery steal syndrome which was the sequela of small-for-size syndrome. Emergency splenic artery ligation and re-anastomosis of the hepatic artery successfully muted the portal inflow and boosted the hepatic arterial inflow. Another patient with portal vein thrombosis underwent thrombendvenectomy. Portal inflow was boosted with ligation of portosystemic shunt, which is often present in these patients with portal hypertension. The coexistence of splenic aneurysm and splenorenal shunt required ligation of both in the third patient. The fourth patient, with portal pressure and flow monitoring, avoided ligation of a coronary vein which became a main portal inflow after portal thrombendvenectomy. Management of graft inflow modulation guided selectively by transonic flowmetry or portal manometry was described.

Spontaneous Splenorenal Shunt: An Alternative Cause of Hyperbilirubinemia in Cirrhosis

Purpose: Purpose: To report an alternative cause of hyperbilirubinemia in cirrhosis. Methods: A 47 year old Caucasian male was referred to our GI Clinic for the evaluation of abnormal liver function tests and cirrhosis. His medical history was significant for hypertension treated by lisinopril. He drank 6-8 beers daily for many years, but quit 2 months earlier. He reported persistent jaundice for the previous 6 months, but denied fever or abdominal pain. Physical exam showed mild splenomegaly, otherwise unremarkable. Laboratory data revealed hemoglobin 12 g/dl, MCV 103 fL, platelets 50-70x103/microliter, INR 1.7, B12 and folate normal, AST/ALT were 2xULN, ALP 160 U/L, total bilirubin 6.0 mg/dl with indirect bilirubin 4.1 mg/dl, GGT 20 U/L, haptoglobin <6 mg/dl, and LDH 330 U/L. Ultrasound liver showed splenomegaly (volume 1200cc)and small ascites. Liver biopsy showed cirrhosis with stage 4 fibrosis. Hematology workup failed to find an underlying hemolytic process. CT scan of abdomen showed massive dilation of splenic venous vasculature, suggestive of spontaneous splenorenal shunt, which explained the observed indirect hyperbilirubinemia. Results: The elevation of portal pressure and resistance in cirrhosis leads to an increased gradient between portal pressure and systemic blood flow, potentially initiating portosystemic (PS) shunt formation. The resultant elevation of vascular endothelial growth factor (VEGF) in this setting is crucial for VEGF-dependent angiogenesis for the formation of spontaneous PS shunts. Splenorenal shunt is the most common spontaneous PS shunt in cirrhosis (found in up to 21% of cirrhotics). Esophageal varices are rarely found in the presence of PS shunts. Abdominal CT scan and ultrasound are helpful in diagnosis of spontaneous PS shunt. Hypersplenism in cirrhosis leads to increased hemolysis in the reticuloendothelial system. In the setting of PS shunting, the unconjugated bilirubin will then fail to be cleared by the liver, resulting in the indirect hyperbilirubinemia observed in this case. Spontaneous PS shunts may cause refractory hepatic encephalopathy, intestinal septicemia and Parkinsonism-like features due to manganese deposition in the brain. Thus, identification of spontaneous PS shunt is critical for providing optimal clinical care in cirrhotic patients. Conclusion: Our case indicates that the spontaneous PS shunt (splenorenal being most common) needs to be considered in patients with possible liver cirrhosis who may have indirect hyperbilirubinemia as a predominant clinical feature. An appropriate, expedited workup should then be undertaken.

Acquired hepatocerebral degeneration: clinical characteristics and MRI findings

To determine the prevalence of acquired hepatocerebral degeneration (AHD), its clinical and neuroimaging characteristics and response to treatments. Acquired hepatocerebral degeneration is a chronic encephalopathy with predominant motor signs in the context of severe liver disease. Its clinical picture is not well defined, and its prevalence and risk factors are not well known. Review of a database of 1000 patients with cirrhosis to identify cases of AHD. Clinical and neuroimaging data, follow-up and response to treatments, including liver transplantation, were recorded. Eight patients with AHD were identified. Its prevalence was 0.8% of patients with cirrhosis. The main risk factor for AHD was the presence of portosystemic shunts. Movement disorders, especially a combination of parkinsonism and cerebellar signs were observed in all patients. All AHD cases showed on MRI T1-weighted images hyperintensities in the globus pallidus, and 75% had extrapallidal involvement as well. Antiparkisonian drugs and treatments to prevent acute encephalopathies were ineffective. Three patients who underwent liver transplantation did not experience neurological improvement. Persistence of portosystemic shunts was demonstrated in two cases. Acquired hepatocerebral degeneration is a chronic encephalopathy which occurs in ∼1% of patients with liver cirrhosis and seems related to portosystemic shunts. Its is characterized by a combination of parkinsonism and cerebellar signs. MRI pallidal and extrapallidal lesions are seen in most patients, probably reflecting intracerebral deposits of manganese. Liver transplant did not improve the neurological signs in our patients, perhaps because of the persistence of portosystemic shunts.

Relationship between 99mTc-GSA scintigraphic indices of liver function reserve and portal circulation in patients with chronic liver disease

In order to predict the prognosis or complications of portal hypertension in patients with chronic liver disease, it is important to evaluate both hepatic functional reserve and portal circulation. On (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy, the index of blood clearance (HH15) and receptor index (LHL15) have been widely used to evaluate the hepatic functional reserve. However, the relationship between these indices and portal circulation is unknown. The purpose of this study was to examine the relationship between HH15 and LHL15 and portosystemic shunts evaluated with arteriographic portography or esophagogastroduodenoscopy. A total of 82 patients with chronic liver disease (mean age, 66.7 years) who underwent (99m)Tc-GSA scintigraphy, arteriographic portography, and esophagogastroduodenoscopy were enrolled. HH15 and LHL15 were obtained from dynamic (99m)Tc-GSA scintigraphy. The patients were divided into three groups according to the arteriographic portography findings: group 1, no portal collateral circulation; group 2, mild collateral development; and group 3, moderate to severe collateral development. They were also divided into three groups based on the esophagogastroduodenoscopic findings: group A, no varices; group B, small-caliber varices; and group C, enlarged varices. The Kruskal-Wallis test was used to compare each index among these groups. Receiver operating characteristic (ROC) analysis was used to determine whether each index was an indicator for the presence of portosystemic shunts. Both HH15 and LHL15 differed significantly between groups 1 and 2 and between groups 1 and 3. However, only HH15 differed significantly between groups A and B and between groups A and C. On the basis of the ROC analysis, the HH15 threshold value of 0.62 yielded both excellent sensitivity (83.9%) and specificity (84.6%) for the presence of portosystemic shunts, as evaluated with arteriographic portography. The HH15 threshold value of 0.64 yielded both good sensitivity (66.1%) and specificity (69.2%) for the presence of portosystemic shunts, as evaluated with esophagogastroduodenoscopy, whereas no adequate threshold value of LHL15 was found for the presence of portosystemic shunts. HH15 is a potent indicator of the presence of portosystemic shunts in chronic liver disease.

Liver Graft-to-Recipient Spleen Size Ratio as a Novel Predictor of Portal Hyperperfusion Syndrome in Living Donor Liver Transplantation

Portal hyperperfusion in a small-size liver graft is one cause of posttransplant graft dysfunction. We retrospectively analyzed the potential risk factors predicting the development of portal hyperperfusion in 43 adult living donor liver transplantation recipients. The following were evaluated: age, body weight, native liver disease, spleen size, graft size, graft-to-recipient weight ratio (GRWR), total portal flow, recipient portal venous flow per 100 g graft weight (RPVF), graft-to-recipient spleen size ratio (GRSSR) and portosystemic shunting. Spleen size was directly proportional to the total portal flow (p = 0.001) and RPVF (p = 0.014). Graft hyperperfusion (RPVF flow > 250 mL/min/100 g graft) was seen in eight recipients. If the GRSSR was < 0.6, 5 of 11 cases were found to have graft hyperperfusion (p = 0.017). The presence of portosystemic shunting was significant in decreasing excessive RPVF (p = 0.059). A decrease in portal flow in the hyperperfused grafts was achieved by intraoperative splenic artery ligation or splenectomy. Spleen size is a major factor contributing to portal flow after transplant. The GRSSR is associated with posttransplant graft hyperperfusion at a ratio of < 0.6.

Nonalcoholic Fatty Liver Disease: Cytokine-Adipokine Interplay and Regulation of Insulin Resistance

Nonalcoholic fatty liver disease (NAFLD), the major reason for abnormal liver function in the Western world, is associated with obesity and diabetes and is characterized by insulin resistance (IR). IR is regulated by mediators released from cells of the immune system or adipocytes and proinflammatory cytokines such as tumor necrosis factor-α (TNFα). The importance of TNFα in human and animal fatty liver diseases, both caused by genetic manipulation and overnutrition, has been shown convincingly. Furthermore, neutralization of TNFα activity improves IR and fatty liver disease in animals. Adiponectin is a potent TNFα-neutralizing and anti-inflammatory adipokine and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR. Anti-inflammatory effects of adiponectin are exerted both by suppressing TNFα synthesis and by induction of anti-inflammatory cytokines such as interleukin-10 or interleukin-1–receptor antagonist. Therefore, the balance between various mediators, either derived from the immune system or adipose tissue, appears to play an important role in hepatic and systemic insulin action and in the development of fatty liver disease.

RISK FACTORS FOR INTRAOPERATIVE PORTAL VEIN THROMBOSIS IN PEDIATRIC LIVING DONOR LIVER TRANSPLANTATION

P542 Running title: Intraoperative portal vein thrombosis Pathologic changes of the recipient native portal venous system may cause thrombosis of the portal vein, especially in pediatric living donor liver transplantation (LDLT). This study assessed the utility of Doppler ultrasound for the detection of intraoperative portal vein occlusion and identification of predisposing risk factors in the recipients. 73 pediatric recipients who underwent LDLT at Chang Gung Memorial hospital, Taiwan from 1994 to 2002 were included. Pre-operative and intraoperative Doppler ultrasound (US) evaluation of the portal vein was performed. Age, body weight, native liver disease, type of graft, graft recipient weight ratio (GRWR), type of portal anastomosis, portal velocity, portal venous size and presence of portosystemic shunt were analyzed for statistical significance of predisposing risk factors. Eight episodes of intraoperative portal vein thrombosis, with typical findings of absent Doppler flow in portal vein and prominent hepatic artery with a resistant index lower than 0.5 (P<0.001), were detected during transplantation, which was then corrected by thrombectomy and re-anastomosis. Children age ≤ 1year old (P=0.025), weight ≤ 10 Kg (P=0.024), low portal flow ≤ 7cm/sec (P=0.021), portal venous size ≤ 4mm (P=0.001), and GRWR > 3 (P < 0.017) were all risk factors for intraoperative portal vein thrombosis. Doppler US is essential in the pre-operative evaluation, early detection and monitoring of outcome of the portal vein in liver transplant.

Risk factors for intraoperative portal vein thrombosis in pediatric living donor liver transplantation.

Pathologic changes of the recipient native portal venous system may cause thrombosis of the portal vein, especially in pediatric living donor liver transplantation (LDLT). This study assessed the utility of Doppler ultrasound (US) for the detection of intraoperative portal vein occlusion and identification of predisposing risk factors in the recipients. Seventy-three pediatric recipients who underwent LDLT at Chang Gung Memorial Hospital, Taiwan, from 1994 to 2002 were included. Preoperative and intraoperative Doppler US evaluation of the portal vein was performed. Age, body weight, native liver disease, type of graft, graft recipient weight ratio (GRWR), type of portal anastomosis, portal velocity, portal venous size and presence of portosystemic shunt were analyzed for statistical significance of predisposing risk factors. Eight episodes of intraoperative portal vein thrombosis, with typical findings of absent Doppler flow in portal vein and prominent hepatic artery with a resistant index lower than 0.5 (p < 0.001), were detected during transplantation, which was then corrected by thrombectomy and re-anastomosis. Children age < or =1 yr (p = 0.025), weight < or =10 kg (p = 0.024), low portal flow < or =7 cm/s (p = 0.021), portal venous size < or =4 mm (p = 0.001), and GRWR >3 (p < 0.017) were all risk factors for intraoperative portal vein thrombosis. Doppler US is essential in the preoperative evaluation, early detection and monitoring of outcome of the portal vein in liver transplant.