Effects of transjugular intrahepatic portosystemic shunt (TIPS) on quantitative liver function tests

BACKGROUND/AIMS: The transjugular intrahepatic portosystemic stent-shunt (TIPS) has been established as a new effective treatment for portal hypertension in advanced liver disease. Impairment of liver function due to reduced portal venous perfusion is considered to be a major risk of TIPS, and the shunt leads to an increase in the incidence of hepatic encephalopathy (HE). Known complications, like the increase in the incidence of HE or TIPS stenosis, are diagnosed either clinically or by doppler ultrasound. It is not practicable to use quantitative liver function tests in the diagnostic work-up of HE, and medical or interventional therapy can be established after clinical diagnosis. Still, information is limited about the influence of TIPS on quantitative liver function tests in patients with liver cirrhosis. Therefore, the aim of this prospective study was to assess the effects of TIPS on various liver function tests. METHODOLOGY: Fifteen patients with liver cirrhosis, a hepatopetal portal flow before TIPS, and an uncomplicated course without stenosis after elective TIPS were analysed. Liver function was quantitatively measured using the [14C]aminopyrine breath test (ABT), considered to be independent of hepatic blood flow, the monoethylglycinexylidide test (MEGX), believed to be largely dependent on hepatic blood flow, serum bilirubin, serum albumin, and prothrombin time. Measurements were performed before, 1, 3 and 6 months after TIPS. RESULTS: TIPS decreased the portal venous pressure gradient from 31.0+/-2.0 cm (SEM) H2O to 16.9+/-1.8 cm H2O (p<0.01). One, 3 and 6 months after TIPS there was no significant deterioration of liver function as assessed by ABT, MEGX or serum bilirubin, serum albumin, and prothrombin time compared to baseline values before TIPS. ABT and MEGX were significantly correlated before TIPS (r=0.72; p<0.01) and after TIPS (r=0.76; p<0.05). CONCLUSIONS: These data show no significant deterioration of microsomal liver function as measured by the quantitative liver function tests ABT and MEGX over a period of 6 months after elective TIPS. In particular, there was no significant reduction of the MEGX-test considered to depend predominantly on hepatic blood flow. Thus, there is no need for the quantitative liver function tests ABT and MEGX in the routine management of patients following the TIPS procedure.     

Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment

OBJECTIVE: We assessed the feasibility of contrast-enhanced color Doppler, power Doppler, and spectral duplex sonography for visualization and quantification of flow through transjugular intrahepatic portosystemic shunts (TIPS) in patients in whom the baseline sonographic evaluation was unsatisfactory. SUBJECTS AND METHODS: Thirty-three patients underwent color Doppler, power Doppler, and spectral duplex sonography after TIPS insertion or before TIPS revision (mean time interval +/- SD, 1 +/- 1 day). All sonograms were obtained before and after patients received echo-enhancing contrast material. Sonography was evaluated with regard to presence or absence of flow in the mid portion, portal segment, and hepatic segment of the shunt. The maximal peak velocity was measured in the mid portion of the shunt. For identifying and quantifying stenoses, the percentage of luminal diameter reduction was calculated at the tightest part of the shunt. Shunt angiography and measurements of portosystemic pressure gradients were independently evaluated and compared with the sonographic findings. RESULTS: Flow visualization on unenhanced color Doppler sonography was significantly improved through the use of power Doppler sonography and contrast-enhanced color Doppler and power Doppler sonography (p < .01). Between contrast-enhanced power Doppler and contrast-enhanced color Doppler sonography, a significant difference was found in the portal and hepatic segments (p < .05). All shunt stenoses (n = 8) and occlusions (n = 3) were revealed by power Doppler sonography, whereas color Doppler sonography failed to reveal six of eight stenoses. Compared with unenhanced sonography, the quality of spectral duplex sonography was improved in eight patients after contrast enhancement (p < .05). Maximal peak velocity ranged from 54 to 252 cm/sec (mean +/- SD, 132.7 +/- 52.1 cm/sec) in normal shunts and from 24.5 to 70.0 cm/sec (mean +/- SD, 45.0 +/- 18.9 cm/sec) in stenosed shunts. No correlation was found between maximal peak velocity and portosystemic pressure gradients (r = .28). CONCLUSION: Unenhanced power Doppler and contrast-enhanced color and power Doppler sonography can be helpful in the assessment of TIPS status in patients who previously underwent unsatisfactory sonography. These techniques may allow anatomic evaluation and quantification of shunt stenosis in most patients. Contrast enhancement may also considerably improve the quality of spectral duplex sonography.     

Transjugular intrahepatic portosystemic shunt for the management of severe venoocclusive disease following bone marrow transplantation

Hepatic venoocclusive disease (VOD) is a common, life-threatening complication of bone marrow transplantation (BMT). Portal hypertension is usually present and accounts for many of the clinical manifestations of this syndrome. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT TIPS was performed in six patients with histologically confirmed VOD who had progressive jaundice and ascites. Portal hypertension was improved by TIPS in all patients (mean portal pressure gradient before TIPS, 20.2 +/- 4.6 vs. 6.7 +/- 1.9 mm Hg post-TIPS, P < .004). Three patients who underwent TIPS late in the course of VOD did not demonstrate any clinical improvement after TIPS and expired within 2 weeks of the procedure. The remaining three patients had less advanced disease and demonstrated decreases in serum bilirubin, improvement in coagulopathy, and decreased ascites after TIPS. Two patients subsequently expired, one with persistent histological changes of VOD. The lone survivor continues to do well with resolution of ascites, jaundice, and coagulopathy as of her last outpatient visit. TIPS was an effective method for portal decompression in patients with VOD after BMT, and was associated with clinical improvement in some patients. However, these effects may be transient and may not improve overall survival.     

Lung resection after pneumonectomy for bronchogenic carcinoma

AIMS/BACKGROUND: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short-term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D-sorbitol (S-HCl). METHODS: Twenty-five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady-state, during constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S-HCI before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was directly measured at the level of the right (Er), where TIPS was applied, and of the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t-test for paired data. RESULTS: After application of TIPS, a substantial reduction was observed in PCG (12.1+/-4.2 vs 24.8+/-4.3 mmHg; p<0.001) and Er values (20.6+/-14.8 vs 57.5+/-22.3 %; p<0.001) but not El values (47.4+/-22.0 vs 53.4+/-21.4 %; p=0.178). S-HCl measured 120 min after TIPS opening was not statistically different from pre-TIPS values (389.2+/-212.1 vs 394.6+/-152.7 ml/min; p=0.892), although S-HCl variations in Child-Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). CONCLUSION: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.     

Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined. Hence, we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure. METHODS: Prospective follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted. RESULTS: The portacaval pressure gradient (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6 +/- 2.7 mm Hg; P > 0.001), but increased thereafter and at rebleeding (n = 25) was > 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients developed ascites; the PPG (measured in 19) was always > 12 mm Hg. Increasing the PPG to > 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of patients underwent balloon angioplasty or restenting. However, 80% had again a PPG of > 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed in 31% of patients at 1 year; 21 of 23 patients had a PPG of < 12 mm Hg. CONCLUSIONS: Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained < 12 mm Hg. However, reintervention will be required in most patients within 1 year and again the second year. On the other hand, such portal decompression is associated with an increased risk of hepatic encephalopathy.     

Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.     

Accuracy of portal and forearm blood flow measurements in the assessment of the portal pressure response to propranolol

BACKGROUND/AIMS: The portal pressure response to propranolol varies significantly in individual patients with cirrhosis. At present, propranolol responders can be identified only by measuring the hepatic venous pressure gradient. The aims of this study were: 1) to investigate whether the noninvasive monitoring of portal blood flow by pulsed Doppler ultrasound and forearm blood flow by strain-gauge plethysmography can predict the hepatic venous pressure gradient response to propranolol in patients with cirrhosis, and 2) to analyze the factors that may influence this response. METHODS: Hemodynamic measurements were undertaken in 80 patients with cirrhosis before and after receiving propranolol (0.15 mg/kg i.v., n = 60) or placebo (n = 20). RESULTS: No changes were observed in the placebo group. Propranolol lowered (p < 0.01) hepatic venous pressure gradient from 17.6 +/- 3.8 to 14.7 +/- 3.8 mmHg, portal blood flow from 1122 +/- 363 to 897 +/- 332 ml/min and forearm blood flow from 7.52 +/- 3.1 to 6.12 +/- 2.3 ml/min%. Changes in hepatic venous pressure gradient were correlated (p < 0.01) with those of portal blood flow (r = 0.82) and forearm blood flow (r = 0.54). The reduction in hepatic venous pressure gradient was > 20% in 23 patients ("responders"). The accuracy of portal Doppler flowmetry in identifying responders was higher than that of forearm plethysmography (88.3 vs. 68.3%, p < 0.05). Multivariate analysis proved that previous variceal bleeding was the only factor independently associated with a lack of response to propranolol (relative risk 3.42, 95% CI 1.5-7.4, p < 0.01). Hepatic venous pressure gradient reduction by propranolol was higher in non-bleeders than in bleeders (-19.9 +/- 9.4 vs. -11.3 +/- 8.6%, p < 0.01). CONCLUSIONS: Portal Doppler ultrasound can be used as a reliable surrogate indicator of the hepatic venous pressure gradient response to acute propranolol administration. In addition, our study indicates that this response is mainly influenced by previous variceal hemorrhage.     

Outcome of 100 patients after transjugular intrahepatic portosystemic shunt for variceal hemorrhage

OBJECTIVES: One hundred consecutive patients with recurrent or refractory acute variceal hemorrhage treated with a transjugular intrahepatic portosystemic shunt (TIPS) from June 1990 to June 1993 at Oregon Health Sciences University or the Portland Veterans Affairs Medical Center were evaluated to assess shunt patency and clinical outcome, including complications of TIPS, rebleeding, and survival. METHODS: Success of shunt placement, reduction in portal pressure, complications, survival, recurrent hemorrhage, severity of ascites, hepatic encephalopathy before and after TIPS, and shunt patency were assessed in each patient. RESULTS: The mean follow-up period was 17.7 months (range, 0.1-56.7 months). TIPS was successfully completed in all patients, with a mean reduction in portosystemic gradient from 24 to 11 mm Hg. Major complications occurred in 11 patients, including one death. Survival after TIPS was 85% at 30 days, 71% at 1 yr, and 56% at 2 yr. Variceal bleeding stopped within 24 hours after TIPS in all eight patients with active hemorrhage. Recurrent variceal hemorrhage occurred in 18 patients at a mean of 4.3 months (range, 1-713 days) after TIPS. The cumulative rate of recurrent variceal bleeding was 20% at 1 yr and 25% at 2 yr after TIPS. Recurrent variceal bleeding was associated with shunt stenosis or occlusion in all patients with endoscopically documented variceal hemorrhage, which was successfully managed by reopening obstructed shunts and performing variceal embolization. The prevalence of ascites was significantly reduced among surviving patients evaluated 3 months after TIPS (67 vs 25%, p < 0.005). Three months after TIPS, the incidence of new or worsening hepatic encephalopathy was 20%, but encephalopathy improved in an equal proportion of patients. Seventy-three of 77 (95%) shunts examined for patency were open at the last follow-up examination. However, most shunts required intervention to maintain patency, and only 48% (37 of 77) were primarily patent at a mean of 168 days (range, 2-538 days) of follow-up. Shunt stenosis or occlusion, as determined by venography, became increasingly frequent with longer follow-up (52% at 3-9 months and 70% at 9-15 months). CONCLUSIONS: TIPS is effective in lowering elevated portal pressures in patients with refractory variceal hemorrhage, has acceptable postprocedure complication and mortality rates, ameliorates ascites, and in, a minority of patients, worsens encephalopathy. Shunt stenosis occurs in the majority of patients but can be effectively treated by interventional techniques to maintain patency. The incidence of recurrent variceal hemorrhage is low and is associated with shunt stenosis or occlusion.     

Influence of nutritional status on clinical outcome after acute stroke

PURPOSE: To evaluate the performance of Doppler ultrasound as a screening test for detecting elevated portosystemic gradients in failing transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Twenty-seven of 61 patients who underwent TIPS creation between November 1991 and March 1996 were studied. At routine intervals, angle-corrected velocity measurements of portal venous and intrashunt blood flow (at the portal venous, middle, and hepatic venous levels of the shunt) were obtained. These were compared with portal hemodynamics for diagnostic accuracy in predicting clinically significant elevation of the portosystemic gradient. Venographic and manometric correlations were obtained on all patients available for follow-up and were not limited to those with symptoms or "abnormal" Doppler studies. Receiver-operating characteristic (ROC) curves were done. Linear regression was done to study correlation of shunt velocities with portal pressure, and logistic regression was done to predict shunt stenosis with use of shunt velocities. RESULTS: The most accurate location for shunt velocity measurement was the main portal vein, but this had an area under the ROC curve of only 0.70. Accuracy of any velocity threshold (including maximum shunt velocity) was no greater than 70%. Maximum shunt velocity of less than 60 cm/sec was 93% specific for detecting shunt restenosis, but only 25% sensitive, for an overall accuracy of 64%. High sensitivity (90%) could only be achieved with poor specificity (< 33%). Linear regression revealed poor correlation between shunt or portal vein velocity measurements and portal pressure (/r/ < 0.23 for all). CONCLUSIONS: Intrashunt and portal venous Doppler velocities alone do not accurately predict elevation of the portosystemic gradient on long-term follow-up after TIPS.     

Portal hemodynamics after large-volume paracentesis in patients with liver cirrhosis and tense ascites

Large-volume paracentesis with a plasma expander has been extensively evaluated and shown to be an effective and safe therapy. While hepatic and systemic hemodynamics have been studied extensively, there is little information on portal hemodynamics by duplex Doppler. Portal vein diameter, portal flow velocity, and portal blood flow were measured with duplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There were no significant changes in the portal vein diameter (9.88+/-2.62 mm vs 10.09+/-2.73 mm), portal flow velocity (10.65+/-2.60 vs 10.01+/-2.58 cm/sec), and portal blood flow (488+/-288.9 vs 502+/-73.38 ml/min), before and 24 hr after large-volume paracentesis. Thus, significant changes in portal hemodynamics do not occur after large-volume paracentesis.     

Doppler sonographic assessment of functional response of the right and left portal venous branches to a meal

PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood flow in the right and left portal vein branches before and after a standard meal. We also assessed the functional response of the right and left lobes of the liver. METHODS: Portal blood flow was measured by Doppler sonography in the left and right portal vein branches and main portal trunk in 20 healthy volunteers in both fasting and postprandial states. The ratio between portal blood flow and liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before the meal, a statistically significant difference in portal blood flow volume was observed between the right and left portal branches (p < 0.01). The right PFI (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly different (p < 0.01). The increase in portal venous blood flow after a meal was found to be greater in the left portal branch (128%) than in the right portal branch (78%). The postprandial PFI also differed significantly (right, 1.54 ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that the left lobe of the liver has a better postprandial compliance than the right lobe has.     

Measurement of collateral circulation blood flow in anesthetized portal hypertensive rats

AIMS: The aim of this study was to develop a technique to measure collateral blood flow in portal hypertensive rats. METHODS: Morphological techniques included inspection, casts and angiographies of portosystemic shunts. The main hemodynamic measurements were splenorenal shunt blood flow (transit time ultrasound method), percentage of portosystemic shunts and regional blood flows (microsphere method). In study 1, a model of esophageal varices was developed by ligating the splenorenal shunt. In study 2, morphological studies of the splenorenal shunt were performed in rats with portal vein ligation. In study 3, the relationship between splenorenal shunt blood flow with percentage of portosystemic shunts was evaluated in dimethylnitrosamine cirrhosis. In study 4, secondary biliary, CCl4 and dimethylnitrosamine cirrhosis were compared. In study 5, rats with portal vein ligation received acute administration of octreotide. In study 6, rats with dimethylnitrosamine cirrhosis received acute administration of vapreotide. RESULTS: Blood flow of para-esophageal varices could not be measured. SRS blood flow was correlated with the mesenteric percentage of portosystemic shunts (r = 0.74, P < 0.05), splenic percentage of portosystemic shunts (r = 0.54, P < 0.05) and estimated portosystemic blood flow (r = 0.91, P < 0.01). Splenorenal shunt blood flow was 6 to 12 times higher in portal hypertensive rats, e.g., in portal vein ligated rats: 2.8 +/- 2.7 vs 0.3 +/- 0.1 mL.min-1 in sham rats (P < 0.01), and was similar in the different cirrhosis models but was higher in portal vein ligated rats than in cirrhotic rats (1.2 +/- 0.7 vs 0.6 +/- 0.6 mL.min-1.100 g-1, P = 0.05). Octreotide significantly decreased splenorenal shunt blood flow: -23 +/- 20% (P < 0.01) vs -6 +/- 8% (not significant) in placebo rats. The variation of splenorenal shunt blood flow after vapreotide was significant but not that of the splenic percentage of portosystemic shunts compared to placebo. CONCLUSIONS: The splenorenal shunt is the main portosystemic shunt in rats. The measurement of splenorenal shunt blood flow is easy, accurate and reproducible and should replace the traditional measurement of the percentage of portosystemic shunts in pharmacological studies.     

Transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding in portal hypertension: comparison of emergency and elective interventions

Nonsurgical reduction of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) is widely used for prevention of variceal rebleeding (elective TIPS). Information is limited about the value of emergency TIPS for acute variceal bleeding unresponsive to endoscopic and drug therapy. The aim of the present study was therefore to determine whether the effects and complications differ between emergency and elective TIPS in patients with cirrhosis of the liver. TIPS was performed in 11 patients with acute variceal bleeding unresponsive to endoscopic treatment and 22 patients in stable condition after an episode of variceal bleeding. Clinical examination, blood sampling, Doppler sonography of TIPS flow, and upper gastrointestinal endoscopy were performed at days 1, 7, and 30 and at three-month intervals after TIPS. Mean follow-up was 549 (1-987) days. Bleeding was controlled by emergency TIPS in 10/11 patients. Probability of survival was not different after emergency and elective TIPS (0.73 vs 0.84 at one year). Early rebleeding (< or =2 weeks) occurred more often after emergency TIPS (3/11 vs 0/22 patients; P = 0.03), but there was no significant difference in late rebleeding. Occlusion of TIPS was more frequent after emergency TIPS. Occurrence of TIPS stenoses was identical in both groups (4/11 vs 8/22). De novo or deterioration of preexisting hepatic encephalopathy was similar (18% vs 24%; NS). It is concluded that TIPS is effective for control of acute variceal bleeding unresponsive to endoscopic and drug treatment. Early rebleeding and stent occlusion occurred more often after emergency TIPS. Late rebleeding, complications, and long-term survival did not differ from elective TIPS.     

Portal vein ligation selectively lowers hepatic cytochrome P450 levels in rats

In rats, surgical creation of a portacaval shunt leads to hepatic atrophy and lowered levels of cytochrome P450, the key component of liver enzymes involved with drug metabolism. These effects are largely attributable to diversion of portal blood away from the liver and not to decreased hepatic blood flow. The present study has established a simpler model of portal blood diversion in order to examine the role of portal blood constituents in the regulation of hepatic cytochrome P450. Portal vein ligation was performed on male Wistar rats in which portasystemic anastomoses had been produced by subcutaneous transposition of the spleen. Portal vein ligation resulted in portal hypertension, as evidenced by splenomegaly, and in hepatic atrophy. In liver of rats with portal vein ligation, microsomal cytochrome P450 levels were significantly less than in sham-operated control rats, but cytochrome b5, NADPH-cytochrome c reductase, and glucose-6-phosphatase were unaltered. The activities of four mixed function oxidases also were reduced significantly in the liver of rats with portal vein ligation, the changes being greatest for ethylmorphine N-demethylase, a prototype substrate for the phenobarbital-inducible isoenzyme of cytochrome P450. In contrast, the activity of microsomal heme oxygenase, the rate-limiting step in catabolism of heme to bilirubin, was enhanced after portal vein ligation. Experiments in pair-fed rats showed that the changes observed in liver from rats with portal vein ligation could not be attributed to caloric deprivation. Administration of phenobarbital increased liver mass, cytochrome P450 levels, and mixed function oxidase activities both in rats with portal vein ligation and in controls, indicating that the liver of the ligated rats retained considerable protein synthetic capacity. It appears that hepatic atrophy and lowering of cytochrome P450 levels that follow portal vein ligation are consequences of altered exposure of the liver to factors normally present in portal blood, and that the same alterations may also enhance heme oxygenase activity.     

Creation of transjugular intrahepatic portosystemic shunts with the wallstent endoprosthesis: results in 100 patients

One hundred patients underwent transjugular intrahepatic portosystemic shunt (TIPS) creation for variceal bleeding (n = 94), intractable ascites (n = 3), hepatorenal syndrome (n = 2), and preoperative portal decompression (n = 1). Shunts were completed in 96 patients. Portal vein pressure was reduced from 34.5 mm Hg +/- 7.6 (standard deviation) to 24.5 mm Hg +/- 6.2; the residual portal vein-hepatic vein gradient was 10.4 mm Hg +/- 0.9. Acute variceal bleeding was controlled in 29 of 30 patients. Of the 96 patients who underwent successful TIPS creation, 26 have died and 22 have undergone liver transplantation; the remaining 48 patients have survived an average of 7.6 months. Variceal bleeding recurred in 10 patients. Fifteen patients developed shunt stenosis (n = 6) or occlusion (n = 9). Patency was reestablished in eight of the nine occluded shunts. Seventeen patients developed new or worsened encephalopathy. The authors conclude that TIPS creation is an effective and reliable means of lowering portal pressure and controlling variceal bleeding, particularly in patients with acute variceal bleeding unresponsive to sclerotherapy and patients with chronic variceal bleeding before liver transplantation.     

Fusion variations of pancreatic ducts in patients with anomalous arrangement of pancreaticobiliary ductal system

Portal vein flow was recorded by color Doppler sonography in 31 patients with chronic heart failure and 18 control subjects. Compared with patients showing a forward flow (Group A), those with reversed portal vein flow (Group B) had higher prevalence of tricuspid regurgitation (75% vs. 43%), hepatic congestion (100% vs. 30%) and ascites (50% vs. 18%), and showed higher right atrial pressure (25.3 +/- 3.01 mmHg vs. 11.8 +/- 5.75 mmHg, p < 0.01). In controls, portal vein pulsatility ratio was 0.66 +/- 0.08, in Group A it was 0.46 +/- 0.28 (p < 0.01), in Group B -0.60 +/- 0.19 (p < 0.01). Portal vein pulsatility ratio negatively correlated with right atrial pressure (r = -0.87; p < 0.01). In Group A, hepatic congestion, ascites and tricuspid regurgitation were associated with a higher portal vein pulsatility. This study indicates that portal vein pulsatility ratio reflects the level of impairment of the right heart.     

Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis

BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in the splanchnic and systemic haemodynamics, and subsequent complications, such as bleeding from oesophageal varices, have led to the introduction of long-acting somatostatin analogues in the treatment of portal hypertension. However, reports on the splanchnic and systemic effects of octreotide are contradictory and therefore the aim of the present study was to assess the effects of continuous infusion of octreotide on central and systemic haemodynamics, portal pressures, and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver vein catheterisation. Portal and arterial blood pressures were determined at baseline and 10, 30, and 50 min after a bolus injection of octreotide 100 micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1 h. Hepatic blood flow, cardiac output, central and arterial blood volume, and central circulation time were determined at baseline and 50 min after the start of the octreotide infusion. RESULTS: The mean arterial blood pressure increased during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The central and arterial blood volume (-16%, p < 0.005) and the central circulation time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the cardiac output did not change significantly. The hepatic venous pressure gradient and the hepatic blood flow did not change significantly at any time after infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis. However, these early effects do not exclude the possibility that administration of longacting somatostatin analogues over a longer period may have a beneficial effect.     

Food, obesity and non-insulin-dependent diabetes: are there molecular links?

BACKGROUND & AIMS: The effects of transjugular intrahepatic portosystemic shunt (TIPS) on portal hemodynamics, esophageal and gastric varices, and hepatic function have not been fully defined. The aim of this study was to define prospectively the effects of TIPS on portal pressures and flow, variceal resolution, and hepatic function. METHODS: Pressure and flow measurements were made by angiography and Doppler sonography, respectively. Varices were assessed by endoscopy and angiography. Liver functions were evaluated by a battery of tests. RESULTS: In 100 consecutive subjects, mean portosystemic gradient decreased from 24 to 11 mm Hg (means) (P < 0.001) after TIPS. Recurrent portal hypertension caused by stent thrombosis (n = 5), stent retraction (n = 2), and stent stenosis (n = 51) occurred at 6 months but, by year 5, was not present in survivors (n = 0 of 8). Fundic gastric varices failed to resolve in 6 of 12 cases. Systemic venous pressures of >15 mm Hg, stent dysfunction, and continued alcoholism were risk factors for recurrent hemorrhage. Angiography was superior to endoscopy, which was superior to Doppler sonography for detection of recurrent portal hypertension. Progressive liver failure occurred in 8 patients. CONCLUSIONS: Recurrent portal hypertension caused by stent stenosis occurs commonly in the first 2 years after TIPS. Fundic gastric varices often fail to disappear after TIPS. The effects of TIPS on liver function are unpredictable.     

Usefulness of pulsatile bidirectional cavopulmonary shunt in high-risk Fontan patients

BACKGROUND: A bidirectional cavopulmonary shunt has been performed for the high-risk Fontan patient. It is well known that in the presence of the bidirectional cavopulmonary shunt alone to secure pulmonary blood flow, the central pulmonary artery size decreases over time. We have performed pulsatile bidirectional cavopulmonary shunt (PBCPS), keeping pulmonary blood flow from the ventricle through the stenotic pulmonary valve, or a Blalock-Taussig shunt in patients who do not meet the criteria for the Fontan operation. METHODS: Eleven patients who underwent PBCPS between 1989 and 1993 were reviewed. We compared the results of cardiac catheterization immediately before PBCPS and during the postoperative observation period (310 +/- 257 days). RESULTS: Pulmonary blood flow and arterial oxygen saturation increased significantly after PBCPS (p = 0.01). Pulmonary artery area index showed a tendency to increase (p = 0.11). The mean number of risk factors for the Fontan procedure decreased significantly for 1.8 +/- 1.1 to 0.7 +/- 0.8 after PBCPS (p < 0.05). Overall, 5 of the 11 patients (45.5%) met the criteria for the Fontan procedure, and a fenestrated Fontan procedure was carried out in 4 of them. CONCLUSIONS: The PBCPS is useful for high-risk Fontan patients not only in the staged Fontan operation, but also as definitive palliation.     

Glucagon and insulin metabolism in cirrhotic patients

BACKGROUND/AIMS: The aim of this study was to investigate glucagon and insulin metabolism in order to clarify the mechanisms that lead to hyperglucagonemia and hyperinsulinemia in cirrhosis. METHODOLOGY: Splanchnic output and metabolic clearance rates were studied in 16 cirrhotic patients and 5 non-cirrhotic controls. Splanchnic glucagon and insulin output into the portal circulation were calculated by the difference between portal venous and systemic arterial concentration multiplied by portal plasma flow. The metabolic clearance rate was calculated as the ratio of output to systemic arterial concentration. Portal blood flow was measured by continuous local thermodilution. RESULTS: Arterial glucagon levels were higher in cirrhotics than in controls. Glucagon output was triple of that found in controls (52.4 +/- 7.0 vs 17.7 +/- 2.9 ng/min, p < 0.05). Both groups exhibited similar metabolic clearance rates of glucagon. Systemic arterial insulin values were higher in cirrhotics than in non-cirrhotics. Insulin output was not significantly different between the two groups. However, metabolic clearance of insulin in cirrhotics was reduced to one half of the rate found in controls (237.0 +/- 39.8 vs. 450.5 +/- 17.5 mL/min, p < 0.05). CONCLUSIONS: Hyperglucagonemia in cirrhotic patients results from increased pancreatic output, while hyperinsulinemia results from decreased insulin clearance.