[Probiotics in acute pancreatitis--a randomised, placebo-controlled, double-blind study]. / Probiotika u akutni pankreatitidy--randomizovaná, placebem kontrolovaná, dvojite slepá studie.

INTRODUCTION: Infections accompanying pancreatitis, particularly pancreatic necroses, represent a serious complication associated with worsening of the disease prognosis. The aim of our study was to explore whether this complication could be prevented by administering a probiotic. METHODS: The probiotic was administered to 7 patients and placebo to 15. The study was discontinued early following the release of the Propatria study results. RESULTS: There was no death in our patient sample and there was no difference between the two groups in microbial colonisation or the length of hospitalization. However, a reduction in endotoxin levels on day 7 and 10 of the hospitalization was observed in the probiotic-treated group. CONCLUSION: Based on the current knowledge, administration of probiotics in this indication is contraindicated. Nonetheless, reduction in endotoxin levels suggests a positive effect of probiotics on bacterial translocation, the importance of which should be evaluated in the future.

[Liver cirrhosis and its treatment]. / Jaterní cirhóza a její lécba.

Cirrhosis is an end-stage liver disease. It is necessary to always search for the cause, attempt to initiate suitable causal treatment and assess the severity of hepatopathy by evaluating hepatic functional reserve (according to the Child-Pugh classification). It is necessary to continually monitor possible complications of cirrhosis, some can be prevented. Regular clinical and laboratory monitoring as well as ultrasound and endoscopic examinations are required. The paper discusses the treatment of the disease as well as its complications. Cure can only be achieved with a liver transplant; this option should be evaluated by a hepatologist in each patient with functional classification B or with serious complications of portal hypertension mentioned above. Treatment standards compiled by the Czech Society of Hepatology (http://www.ceska-hepatologie.cz) offer the basic algorithms of correct diagnosis and treatment.

[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.

[Diagnostics and therapy of hepatorenal syndrome. Recommendations of of the working group on portal hypertension of the Czech Hepatology Society and the J. E. Purkinje Czech Medical Society]. / Doporuceny postup pro diagnostiku a lécbu hepatorenálního syndromu. Doporucený postup vypracovaný skupinou pro portální hypertenzi pri Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne a schválený výborem Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne.

Hepatorenal syndrome is a functional renal failure in patients with advanced cirrhosis and portal hypertension or acute liver failure. It is caused by extreme vasoconstriction in renal arterial bed. Type I HRS presents as an acute renal failure, while type II HRS is chronic alteration of renal function in patients with refractory ascites. Prognosis of HRS is very poor with survival reaching several weeks in patients with HRS type I. Causal treatment is liver transplantation, other treatment options include use of splanchnic vasoconstrictors (terlipressin) together with plasmaexpansion (albumin) and TIPS. It is important to exclude nephrotoxic medication (non-steroid anti inflammatory drugs, aminoglycosides) and properly treat all infective complications in prevention of HRS.

[The diagnostics and therapy of hepatic encephalopathy. Recommendations of of the working group on portal hypertension in the Czech Hepatology Society and the J. E. Purkinje Czech Medical Society]. / Diagnostika a lécba jaterní encefalopatie. Doporucený postup vypracovaný skupinou pro portální hypertenzi pri Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne a schválený výborem Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne.

UNLABELLED: Hepatic encephalopathy (HE) is a set of reversible neuropsychic features which occur in connection with hepatic cirrhosis or acute hepatic failure. We distinguish manifest HE (with clinical symptoms) and minimal FE (normal clinical finding, abnormal psychometric or neurophysiologic exam). The diagnosis is clinical or laboratory one. From the auxiliary examinations in common practice the number connection test is sufficient. THERAPY: Presence of hepatic encephalopathy should lead to the consideration of the possibility to solve basic disease by hepatic transplantation. Conservative therapy lies in 1. Basic disease elimination, 2. Measures lowering the ammonia level in blood--optimalization of protein intake, administration of indigestible disaccharides (lactulose, lactitol) and fill sterilisation by antibiotics (Rifaxin, Metronidazol), ornitine-aspartate administration, 3. Influencing the changes in amino acid metabolism (administration of branched chain amino acids--BCAA). Prognosis depends on the advancement of the disease, after hepatic transplantation the clinical symptoms of HE are mostly fully reversible.

[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.

[Diagnostics and treatment of hepatocellular carcinoma. Recommendations of the Portal Hypertension Working Group of the Czech Hepatology Society and the J.E. Purkinje Czech Medical Society ]. / Diagnostika a lécba hepatocelulárního karcinomu.

Hepatocellular carcionma (HCC) is almost exclusively associated with liver cirrhosis as a significant HCC risk marker in advanced countries. Applicable therapy depends on early diagnosis, and risk patients should be screened for the presence of HCC on a regular basis. Liver ultrasound and determination of alpha-fetoprotein serum levels (AFP) are the screening methods used. Spiral CT is the most often used method for HCC staging. Non-invasive methods may under certain circumstances replace aimed biopsy. There are 3 basic curative therapies for the early stage of HCC: liver transplantation, surgical resection and different methods of local destruction of tumour (i.e., ethanolisation, thermoablation, etc.). Patients at medium stage of HCC may profit from chemoembolisation. Current available systemic chemotherapy is ineffective. Patients with advanced HCC are treated symptomatically. Patient survival prognosis after the application of one of the above treatment methods may be similar with that for HCC free cirrhosis patients, however, prognosis for advanced HCC patients is bad, with survival period from one to nine months.

[Principles of conservative treatment of severe acute pancreatitis]. / Zásady konzervativní terapie tezké formy akutní pankreatitidy.

The main principles of conservative treatment of severe acute pancreatitis include early diagnosis of the disease, diagnosis of its severe form and assessment of the etiology of pancreatitis, replacement of fluids, adjustment of the milieu intérieur, administration of antibiotics in patients with confirmed necroses, in particular if they exceed 25 - 30%, early endoscpic treatment of pancreatitis with a biliary etiology, adequate nutrition, prevention and treatment of complications. The diagnosis of pancreatitis is based on clinical examination, biochemical evidence of elevated amylase and lipase concentrations and on the imaging of the pancreas. In the severe form necroses of the pancreas are present or other local complications and/or organ dysfunction. As regards assessment of the etiology rapid diagnosis of biliary pancreatitis is fundamental as it leads to therapeutic consequences. Fluid replacement should not be discontinued even during transport and diagnostic procedures. Infection remains the main cause of mortality in patients who got over the hypovolaemic stage of pancreatitis. Antibiotics are therefore indicated in all patients with necroses or biliary infection. Systemic complications include renal failure, pulmonary failure, coagulopathy, cardiac and hepatic failure--frequently manifested as combined multiple organ dysfunction. Local complications such as pseudocysts, abscesses, compression conditioned stenoses of the bile ducts or haemorrhage from impaired visceral arteries are treated as a rule in an interdisciplinary manner with preference of less invasive procedures. Clinical deterioration of patients in particular the development of multiple organ failure in patients with extensive infiltrates and necroses is caused in the great majority of cases by infection of necroses and is an indication for early, usually surgical intervention.

Antagonistic roles for CTLA-4 and the mammalian target of rapamycin in the regulation of clonal anergy: enhanced cell cycle progression promotes recall antigen responsiveness.

CD4(+) T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4(+) T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response.

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.

The role of clonal anergy in the avoidance of autoimmunity: inactivation of autocrine growth without loss of effector function.

Exposure of mature CD4+ T cells in the peripheral immune system to peptide-antigen/MHC complexes in the absence of a threat of infection induces tolerance to the antigen as a result of both a decreased clonal frequency (peripheral deletion) and the induction of proliferative unresponsiveness (clonal anergy) in the survivors. Interestingly, Th 1-like effector functions are not automatically blocked after the development of clonal anergy. Thus, anergic T cells have the capacity to mediate Th 1-like helper activities if allowed to accumulate to high frequency. In this article, we examine those factors important to the development of tolerance versus immunity against protein antigen, and speculate on the relationship that exists between effective peripheral tolerance induction and the avoidance of autoimmune disease.

[Transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of symptomatic portal hypertension]. / Transjugulární intrahepatální portosystémový zkrat (TIPS) pri lécbe symptomatické portálni hypertenze.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is the creation of a percutaneous portosystemic anastomosis which is used as an alternative method of surgical portosystemic shunts and endoscopic treatment in the therapy of complications of portal hypertension. The objective of the present work was to summarize experience with TIPS in 100 patients. METHODS AND RESULTS: In 1992-1995 the authors treated 100 patients with symptomatic portal hypertension by TIPS. To create the shunt in 84% patients a spiral Z stent was used, in the remainder a Wallstent. In 86% patients the indication for TIPS was haemorrhage associated with portal hypertension and in 14% refractory ascites. TIPS was implemented in 98% patients. The pressure in the portal vela was not reduced on average to 58% of the original value. Haemorrhage was not stopped in one of 7 patients. Haemorrhage from varices reappeared in 7% patients indicated on account of repeated haemorrhage and was always associated with the finding of chronic stenosis of the shunt. The mortality in conjunction with the procedure was 4%, the mortality within 30 days after operation was 8%. Uncontrollable encephalopathy developed in 3% of the patients. Primary patency of the shunt created by the spiral Z stent was 85% after 6 months, after 12 months 72% and thus does not differ from primary patency when Wallstents are used, as reported in the literature. CONCLUSIONS: TIPS is an effective method to reduce the pressure in the portal vein in portal hypertension. The main limiting factor of the method is stenosis of the shunt due to hyperplasia of the neointima. Stenoses of the shunt can be effectively dilated by percutaneous balloon angioplasty.

[Transjugular intrahepatic portosystemic shunt]. / Transjugulární intrahepatický portosystémový zkrat.

The transjugular intrahepatic portosystemic shunt (TIPS) is a relatively new method of creating a portosystemic shunt using a needle, angioplasty balloon catheters and expandable metallic stents. During a 6-month period, the authors have performed TIPS, using the spiral Z-stent--another modification of the Gianturco-Rósch stent--in 13 patients with portal hypertension. The procedure was technically successful in all patients. Portal pressure decreased by 6 mmHg in one group of patients with 9-10 mm stents, and by 12 mmHg in another group using 12 mm stents. Control of variceal bleeding or resolution of refractory ascites was evident in 11 of the 13 patients.