[Diabetes mellitus and the liver cirrhosis]. / Diabetes mellitus a jaterní cirhóza.

Patients with liver cirrhosis have increased risk of diabetes mellitus development, especially when the underlying disease is hereditary hemochromatosis, autoimmune hepatitis, non-alcoholic steatohepatitis or chronic hepatitis C. Patients with associated diabetes according to liver cirrhosis complications have worse prognosis and the therapy is influenced by both diseases. The authors bring short review of particular diseases, diagnosis and treatment strategy.

[Survival of patients after TIPS in the University Hospital Hradec Kralove]. / Prezívání nemocných po TIPS ve Fakultní nemocnici Hradec Králové.

AIM: To analyze survival of patients after TIPS (transjugular intrahepatic portosystemic shunt). PATIENT SAMPLE AND METHODOLOGY: Between September 1992 and August 2010, TIPS was created in 848 patients of the University Hospital Hradec Kralove. These patients were divided into groups. Survival was analyzed using Kaplan-Meier survival curves. Differences between groups were evaluated using log-rank test. RESULTS: Ten percent of patients do not survive one month after TIPS, 40% of patients survive 5 years and 20% of patients survive 10 years. There were statistically significant differences between groups divided according to Child-Pugh classification (A vs B p = 0.0053; B vs. C p < 0.0001), indication for surgery [prevention of bleeding recurrence differed from refractory ascites (p = 0.0001) and the indication to stop acute bleeding (p = 0.026)]; aetiology of the liver disease [patients with alcoholic cirrhosis differed from patients with Budd-Chiari syndrome (p < 0.0001) and from patients with chronic viral hepatitis (p = 0.024)]. CONCLUSION: Survival of patients after TIPS is influenced by Child-Pugh score, indication and aetiology of the liver disease.

[The impact of secondary insertion of ePTFE-coated stent on sustainable TIPS patency]. / Vliv sekundárniho zavedení ePTFE potahovaného stentu na udrzdení pruchodnosti TIPS.

OBJECTIVE: Retrospective evaluation of the effect of secondary insertion of ePTFE-coated stent in the treatment of TIPS dysfunction versus other current options (simple angioplasty, insertion of additional non-coated stent). PATIENT SET AND METHODOLOGY: From the beginning of 2000 to the end of 2004, there were 121 interventions for TIPS dysfunction performed in our centre in which a non-coated stent was used to make up the shunt at the time of intervention. Depending on the type of intervention, the patient set was divided in 4 groups: simple angioplasty (52 cases, 43%), insertion of non-coated stent (35 cases, 28.9%), insertion of non-dedicated ePTFE-coated stent (15 cases, 12.4%), and insertion of dedicated ePTFE-coated stent (19 cases, 15.7%). All patients were monitored on a regular basis after the intervention for shunt patency with the use of clinical examination and Doppler ultrasonography, or also portal venography. Primary shunt patency after the intervention was evaluated in all four groups by Kaplan-Meier analysis. The primary shunt patency results after the intervention were compared with the use Cox F text and logrank test. RESULTS: The intervention was successful in 120 cases (the overall technical success rate of all interventions was 99.2%). The primary shunt patency was 49.7 % after 12 months and 25.3 % after 24 months following sole angioplasty intervention; 74.9% after 12 and 64.9% after 24 months following intervention involving the insertion of non-coated stent; 75.2 % after 12 months and 64.5% after 24 months following intervention involving the insertion of non-dedicated ePTFE-coated stent, and 88.1% after 12 months and 80.8% after 24 months following intervention involving the insertion of a dedicated ePTFE-coated stent. A statistically significant improvement in shunt patency was obtained in the group of interventions involving the insertion of dedicated ePTFE-coated stent and in the group of interventions involving the insertion of non-coated stent as compared with the group of interventions involving sole angioplasty (p < 0.01). CONCLUSION: From among all the currently used methods of therapeutic intervention for TIPS dysfunction, the best, the best subsequent TIPS patency was obtained after intervention involving insertion of dedicated ePTFE-coated stent.

[Dysfunction of transjugular intrahepatic portosystemic shunt (TIPS) and applicable solutions]. / Dysfunkce transjugulární intrahepatální portosystémové spojky (TIPS) a jelí resení.

A synoptic article providing a comprehensive view of TIPS dysfunction. The article covers current terminology, definition, etiology, pathogenesis, diagnostics, therapy and prevention of TIPS dysfunction.

[MELD score in prediction of early mortality in patients suffering refractory ascites treated by TIPS]. / MELD skóre v predikci casné mortality u nemocných s refrakterním ascitem lécených pomocí TIPS.

UNLABELLED: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is now well established in the treatment of complications of symptomatic portal hypertension such as acute or recurrent variceal bleeding, refractory ascites and Budd-Chiari syndrome. In some patients with refractory ascites who belong to group C according to Child-Pugh classification (score around 12), the indication of the procedure could be very questionable and early mortality is quite high. However, in some cases, the subgroup of such risky patients can profit from TIPS. Child-Pugh classification is used for the stratification of the patients routinely. During the last decade other scoring systems occured to bring a better prognostic value. MELD (Model for End stage Liver Disease) score, based only on laboratory values is one of them. Comparison of these two scoring systems in patients treated by TIPS in previous trials brought certain discrepancy, but MELD score seems to be better in predicting early mortality. The aim of our study was to determine retrospectively the predictive accuracy of MELD score for the early mortality in comparison to Child-Pugh score in patients treated for refractory ascites by TIPS. METHODS: We evaluated 110 patients (mean age 55 years) with liver cirrhosis (61% of patients with alcoholic etiology), who underwent TIPS for refractory ascites in our center from September 1992 to December 2003. MELD and Child-Pugh score was calculated and then compared between groups with early (one month), three month and one year mortality, and those who survived over this period (one, three and twelve months), comparing MELD and Child-Pugh score (ROC analysis and Student's T test were used). RESULTS: Mean follow up was 23 months. Average MELD score in the whole group was (16). In patients, who died within one month the score before TIPS was 21, three months 20 and 18 one year. Comparing MELD score between subgroups and then Child-Pugh score, only for MELD score there was a statistically significant difference (p < 0.05) in one month. Using ROC (AUC) analysis, discriminant power of MELD score was superior to Child-Pugh score for one (0.73 vs 0.63) and three month (0.73 vs 0.67) mortality. The discriminant power for one year mortality was low in both scores. CONCLUSION: MELD scoring system is a better tool to predict the risk of early mortality in patients with refractory ascites treated by TIPS than Child-Pugh classification. The discriminant power was low in both scores in one year horizon.

[Budd-Chiari syndrome and TIPS--twelve years' experience]. / Budduv-Chiariho syndrom a TIPS--12 let zkuseností.

BACKGROUND: Massive thrombosis of hepatic veins is clinically the most serious type of Budd-Chiari syndrome (BCS). Ischemic impairment is the basic problem in case of acute or fulminate course of BCS. Restitution of blood drainage within the liver is a key therapeutic approach in such situation. In chronic course of the disease, symptoms of portal hypertension as ascites, G1 bleeding or hepatorenal syndrome are more common. The portosystemic shunt leads both to blood outflow restitution and to the decrease of portal hypertension. TIPS is a promising method due to minimal perioperative risk for the patient in critical situation and also due to its easiness of use. The aim of our study was to determine the clinical outcome in patients with BCS treated by TIPS in a retrospective analysis. METHODS AND RESULTS: During 12 years 23 patients with intraparenchymal thrombotic occlusion of hepatic veins were treated using TIPS, 17% were children, only 4 patients (17%) were men, the median age was 33.3 years (range 13 to 75 years). One third of the procedures was performed as urgent. In 2/3 of patients thrombosis developed in relation to myeloproliferative syndrome, in nearly 1/3 the origin of thrombosis was not detected. In 2 patients a defect of coagulation was revealed. In the first 11 patients the bare stent was used, the consecutive 12 patients received the ePTFE covered stent (stentgraft). Six patients died during follow-up: I due to fulminate liver failure, 2 due to liver failure caused by acute shunt occlusion, 1 due to the progression of the underlying hematooncological disease; the reason of death in 2 patients was not known. One patient was treated by OLTx during follow-up. The 17 surviving patients are in good condition with good shunt function although they need anticoagulant therapy and intermittent reinterventions. The average period between revisions was 2-3 years, 2 patients had no revision of TIPS for 4 years. The use of ePTFE covered stents had no effect on the number of early occlusions (approx. 18%), the occurrence of late stenoses and occlusions was substantially decreased (p=0.04, log-rank test). CONCLUSIONS: Standing on this experience we consider TIPS, in accordance with literature data, an advantageous therapeutic approach in Budd-Chiari syndrome caused by massive liver vein thrombosis. If the follow up treatment is rigorous, the TIPS usually ensures the necessary perfusion and the function of the liver So it may spare the patients of objectionable liver transplantation.

[Hepatic encephalopathy after TIPS--retrospective study]. / Jaterní encefalopatie po TIPS--retrospektivní sledování.

UNLABELLED: Hepatic encephalopathy (HE) is the main neuropsychiatric complication in cirrhosis of the liver. It develops slowly, begins by alteration of sleep and proceeds via flapping tremor to sopor, coma. Among known factors which promote its development are age, high dietary protein intake, haemorrhage into the GIT and the use of sedatives. Transjugular portosystemic anastomosis (TIPS) as a therapeutic method in complications of portal hypertension is associated with a higher incidence of HE. The objective of the work was to assess by retrospective investigations of patients with cirrhosis of the liver after TIPS the incidence of clinically significant HE and identify risk factors for the development of HE. MATERIAL AND METHODS: The group comprised 256 patients with cirrhosis of the liver after TIPS. This number included 59 diabetic and 197 non-diabetic patients, 7 patients suffered from chronic renal insufficiency and were in a regular dialyzation programme. The presence of HE was evaluated clinically. RESULTS: HE was found in 51% patients above 60 years of age, vs. 27% in younger patients (p = 0.002). The authors did not observe a difference in the incidence of HE in relation to sex, stage of cirrhosis, diameter of the stent nor the drop of the portosystemic gradient. In diabetic patients HE developed in 45.8% (27 of 59), as compared with 30% (59 of 197) in non-diabetic patients (p = 0.02). Multivariance analysis revealed however that the group of diabetic patients had a higher average age and thus the incidence of HE was statistically significantly conditioned by age and not by the presence of diabetes. CONCLUSION: The risk group for HE in our patients were those above 60 years of age and patients with another than ethylic etiology of liver cirrhosis. There was no direct relationship between the development of HE and other investigated parameters. Although there was no difference in the incidence of HE in relation to the diameter of the inserted stent or portosystemic gradient and its reduction, in case of unsuccessful conservative treatment with lactulose and diet, HE can be resolved by narrowing of the shunt by insertion of a reducing stent.

[Effect of transjugular portosystemic shunt on insulin resistance]. / Vliv transjugulární portosystémové spojky na inzulinovou rezistenci.

UNLABELLED: Patients with cirrhosis of the liver suffer from hyperinsulinaemia and a certain degree of insulin resistance. More frequently than in the rest of the population they have diabetes. Transjugular intrahepatic portosystemic shunts (TIPS) as a therapeutic method in complications of portal hypertension lead to rapid haemodynamic changes in the liver. The objective of the submitted work was to assess whether TIPS has an impact on insulinaemia and whether it influences insulin resistance in patients with cirrhosis of the liver. GROUP AND METHODS: The authors evaluated a group of 22 patients with cirrhosis of the liver (10 diabetics and 12 subjects without diabetes) indicated for TIPS. They investigated the insulin and C-peptide concentration in blood obtained by catheterization from the hepatic and portal vein before and after TIPS and in the peripheral blood before TIPS, 1 hour, 1 day, 1 week and 1 month after TIPS. The insulin resistance was examined by the method of the hyperinsulin euglycaemic clamp (HEC) before TIPS, 1 day, 1 week, and 1 month after TIPS. The levels of C-peptide and insulin were assessed by the IRMA method. The blood sugar level in HEC was measured by means of a Hemocue apparatus. The results were evaluated by the non-parametric Wilcoxon test for two dependent samples. RESULTS: Both groups (diabetics and non-diabetics) were comparable as to age, sex, etiology of liver cirrhosis and indication for TIPS. After introduction of TIPS a change of insulin clearance occurred (p = 0.01) and a change of the insulin level in the hepatic vein immediately after TIPS (p = 0.02). Insulin clearance before TIPS was 37-90% (median 54%) and after TIPS it declined to 0-79% (median 38%) (p = 0.01). Already 1 hour after the operation the authors observed a rise of the insulin level in peripheral blood as compared with baseline values (p = 0.002). Statistically significant hyperinsulinaemia persisted one month after TIPS (p = 0.005). Values of C-peptide did not change significantly in time, neither in the hepatic vein nor in the peripheral blood. On examination of IR no statistically significant changes occurred after TIPS. On evaluation of different groups of diabetics and non-diabetics the IR was more marked in patients with DM (mean M = 1.7 mg/kg/min.) than in patients without DM (3.7 mg/kg/min.) (p = 0.03). The authors did not record significant changes of IR in time in different groups. Compensation of DM was not influenced by TIPS. The fasting blood sugar levels before TIPS and 1 month after TIPS were comparable. CONCLUSION: After TIPS a rise of the insulin level in peripheral blood occurred due to the reduced insulin clearance in the liver. Despite hyperinsulinaemia which persisted for one month after the operation, the insulin resistance did not deteriorate. Compensation of diabetes was not affected by TIPS.

Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt.

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy with Iridium-192 in the prevention of restenosis caused by neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS).Materials and Methods: The endovascular brachytherapy with high dose rate automatic afterloading system was performed in six patients with recurrent of stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3 millimeter (mm) from the source axis to the stenotic vessel segment in five patients with spiral Z-stent, and 15 Gy at 5 mm in one patient with Wallstent.Results: Follow-up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated vessel segment, diagnosed 71 days after endovascular brachytherapy by doppler ultrasound. All other patients were, during the follow-up time, without restenosis in the irradiated vessel segment. Radiation-associated side effects were not observed.Conclusions: Endovascular brachytherapy of TIPS is technically feasible and may be done as a part of the percutaneous revision of the shunt. This pilot study may be the largest experience of treating TIPS restenosis in humans to date. For definitive conclusions, a lot of studies are needed.

Value of Doppler sonography in revealing transjugular intrahepatic portosystemic shunt malfunction: a 5-year experience in 216 patients.

OBJECTIVE: The purpose of the study was to evaluate the long-term clinical efficacy of Doppler sonography in revealing failure of transjugular intrahepatic portosystemic shunts (TIPS). SUBJECTS AND METHODS: During a 5-year period, 1192 Doppler examinations were performed in 216 patients with TIPS. No regular follow-up shunt venography was performed. Doppler examinations were retrospectively compared with the results of shunt revisions. Sonograms with negative findings were compared with the patients' clinical status so that the number of false-negative sonographic findings leading to an episode of shunt failure (recurrence of gastrointestinal bleeding or ascites) could be ascertained. Sonographic parameters assessed included diameter, velocity, flow volume, and congestion index of the portal vein; and shunt velocities. RESULTS: Doppler sonography revealed shunt occlusion in 25 of 26 angiographically proven cases (sensitivity, 96%). The combination of velocity criteria (peak intrashunt velocity > or =250 cm/sec, maximum velocity in the portal third of the shunt < or =50 cm/sec, or maximum portal vein velocity less than or equal to two thirds of the baseline value) revealed shunt stenosis in 103 of 110 cases (sensitivity, 94%). Doppler sonography missed a significant shunt stenosis that led to an episode of gastrointestinal bleeding or ascites recurrence in only seven cases. The congestion index of the portal vein showed significant differences between patent and malfunctioning shunts (p < 0.001). CONCLUSION: Doppler sonography is an effective primary imaging method for long-term follow-up of patients with TIPS.

Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt.

PURPOSE: To evaluate the technical feasibility and efficacy of endovascular brachytherapy with Iridium-192 in the prevention of restenosis caused by neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: The endovascular brachytherapy with high dose rate automatic afterloading system was performed in six patients with recurrent of stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3 millimeter (mm) from the source axis to the stenotic vessel segment in five patients with spiral Z-stent, and 15 Gy at 5 mm in one patient with Wallstent. RESULTS: Follow-up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated vessel segment, diagnosed 71 days after endovascular brachytherapy by doppler ultrasound. All other patients were, during the follow-up time, without restenosis in the irradiated vessel segment. Radiation-associated side effects were not observed. CONCLUSIONS: Endovascular brachytherapy of TIPS is technically feasible and may be done as a part of the percutaneous revision of the shunt. This pilot study may be the largest experience of treating TIPS restenosis in humans to date. For definitive conclusions, a lot of studies are needed.

Vascular hyporesponsiveness to vasodilators in rats with cirrhosis.

BACKGROUND/AIMS: In cirrhosis, the activation of nitric oxide and prostacyclin contributes to vasodilation, and ATP-sensitive K+ (KATP) channel activation or L-type calcium (Ca2+) channel inhibition may also play a role in this process. At the same time in cirrhosis, certain endogenous mechanisms may be stimulated which limit the influence of vasodilator mechanisms on vascular tone, thus altering vascular responses to exogenous substances such as nitric oxide donors, exogenous prostacyclin, KATP channel openers or L-type Ca2+ channel blockers. The aim of the present study was to examine the arterial depressor to these exogenous substances in normal rats and in rats with secondary biliary cirrhosis. METHODS: Arterial depressor dose-response curves to nitroprusside (a nitric oxide donor, 5-60 micrograms.kg-1.min-1), prostacyclin (0.5-5 micrograms.kg-1) and aprikalim (a KATP channel opener, 10-200 micrograms.kg-1) were obtained in both groups. The effects of different L-type Ca2+ channel blockers, i.e. nicardipine (a dihydropyridine, 0.02-0.5 mg.kg-1), diltiazem (a benzothiazepine, 0.5-5 mg.kg-1) and verapamil (a phenylalkylamine, 0.02-0.2 mg.kg-1. min-1), were also studied. RESULTS: Cirrhosis produced hyporeactivity to the arterial depressor effect of all doses of nitroprusside, the lowest dose of prostacyclin and the highest doses of aprikalim or diltiazem. Cirrhosis did not significantly change depressor responses to nicardipine or verapamil. CONCLUSIONS: Rats with cirrhosis are hyporeactive to exogenous nitric oxide, prostacyclin, KATP channel opener and benzothiazepine (an L-type Ca2+ channel blocker). Therefore, cirrhosis-induced mechanisms seem to limit the decrease in vascular tone by most vasodilators. However, these mechanisms appear to be more marked in nitric oxide-mediated vasodilation than in other vasorelaxation mechanisms.

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.