Bleeding in portal hypertension.

Liver cirrhosis is the most common reason of clinically significant portal hypertension in the western countries. Portal vein or hepatic veins thrombosis is less common. Variceal bleeding is the most severe life threatening complication of portal hypertension. Appropriate treatment includes initial general management, fluid replacement and hemosubstitution, antibiotic prophylaxis, vasoactive medication and endoscopic treatment. Transjugular intrahepatic portosystemic shunt (TIPS) is standard option in case of first line treatment failure. Dedicated esophageal metal stent or balloon tamponade could be used as a bridge to the TIPS or in case of TIPS contraindication. Non selective beta-blockers and endoscopic therapy are used in primary and secondary prophylaxis.

Chronic cholestatic liver diseases - Primary biliary cholangitis and Primary sclerosing cholangitis.

Cholestasis is defined as hepatocyte and cholangiocyte bile excretion failure or failure of bile transport to the duodenum. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis as chronic progressive cholestatic diseases are the common reasons of chronic cholestasis. Altogether with cholestatic laboratory picture the pruritus, liver osteodystrophy and fatigue are associated symptoms in both diseases. All associated symptoms and complications are needed to be diagnosed and treated early. In case of liver cirrhosis complicatons of accompanied portal hypertension should be treated and liver transplantation must be considered in all those patients. Diagnosis of PBC is based on cholestatic laboratory features, animitochondrial antibody positivity or typical histological patern. Most patients are asymptomatic in time of diagnosis. First line therapy is ursodeoxycholic acid. In case of first line therapy failure, the prognosis is unfavourable. In this case, second line therapy must be considered. In case of PSC the diagnosis is based on MRCP finding mainly, laboratory test and liver biopsy in some cases. Progressive inflamatory and fibrosing impairment affecting intrahepatic and extrahepatict biliary ducts and strong association with inflamatory bowel disease, especially ulcerative colitis is typical for PSC. Endoscopic therapy with dilatation of dominant structure is crucial. The effect of pharmacotherapy is still being discussed and ursodeoxycholic acid could be used. During follow up patients are in the risk of bacterial cholangitis and malignant tumor development (cholangiogenic and colorectal carcinoma mainly). In PSC patients the severe pruritus and reccurent bacterial cholangitis could be an indication for the liver transplantation.

Recommended fluid intake and evidence-based medicine.

Abundant drinking of fluids at any occasion became popular in wealthy society in last decades. It is referred to asserted beneficial health effects, but rationale of these recommendations is disputed in expert environment as hardly traceable and tenable. Authors of the article analyse theoretical issues as well as empiric literary evidence for the current popular recommendation. They find them unfounded and difficult to be defended and the risks of transitive hypo-hydration overestimated. Moreover, they alert true risks of water poisoning we meet not quite rarely in common practice.

Observational cohort study of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS).

Introduction and Aim: Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. MATERIALS AND METHODS: A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher's exact test, Chi-square, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. RESULTS: 257 (37.9%) patients developed HE after TIPS. Patients' age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. CONCLUSION: we have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

Transjugular intrahepatic portosystemic shunt is associated with significant changes in mitral inflow parameters.

INTRODUCTION: Liver cirrhosis is associated with hyperdynamic circulation which can result in heart failure. Transjugular intrahepatic portosystemic shunt (TIPS) due to increase of cardiac output is a stressful stimulus for cardiovascular system. Therefore, new methods for early detection of heart failure are needed. Transmitral flow is a marker of diastolic dysfunction. AIM: To analyze short- and long-term effect of TIPS procedure on transmitral flow. MATERIAL AND METHODS: 55 patients (38 men and 17 women, 55.6 ± 8.9 years) with liver cirrhosis treated with TIPS were enrolled in the study. Echocardiography was performed before, 24 h, 7, 30 and 180 days after the procedure. During 6 month follow up 22 patients died. Results. Left ventricle end-diastolic diameter was increasing during the follow-up [baseline: 47 (44.7-51.2) mm, day 7: 50 (46.5-51.3) mm, p < 0.05; day 30: 49.5 (46.7-55.2) mm, p < 0.01; 6 months: 52.5 (48.3-55.2) mm, p < 0.01)]. The peak early filling velocity (E) was significantly increasing [before: 75.5 (60.5-87.3) cm/s, 24 h: 88 (74.3-109.7), p < 0.01; day 7: 89 (81.5-105) p < 0.01; 1 month: 94 (82.7-108.5) p < 0.01; 6 month: 91 (80.1-120.2) p < 0.01]. Peak late atrial filling velocity (A) significantly increased within 24 h after the procedure: 85.1 (76.2-99.5) vs. 91.2 (81.5-104.5) cm/s, p < 0.05. The E/A ratio was increasing during the follow up (baseline: 0.88, 24 h after: 0.89, 1 week: 1.0, 30 days: 1.13, 6 month: 1.06 p < 0.01). CONCLUSION: Hemodynamic changes following TIPS procedure can be monitored using echocardiography. Transmitral flow analysis can serve as a useful tool for evaluating of diastolic function in these patients.

Ursodeoxycholic acid use in lactating female patients is associated with clinically negligible concentrations of this bile acid in breast milk.

In the literature on the safety of ursodeoxycholic acid (UDCA) during breastfeeding, insufficient data has been reported to date. Thus, the aim of our study was to analyze bile acid (BA) concentrations in breast milk in a cohort of patients, treated with UDCA, and with various cholestatic liver diseases. The study was carried out on a cohort of 20 patients with various cholestatic diseases. All the patients were treated with UDCA (500-1500 mg daily). Concentrations of BA, sampled on day 3 after delivery were analyzed using the GS-MS technique, and then compared to untreated women. Total BA concentrations in the breast milk of the UDCA-treated patients were equal to those of the untreated women controls (3.2 ± 1 vs. 3.2 ± 0.2 µmol/L, respectively). The UDCA concentrations in breast milk remained negligible in UDCA-treated patients (0.69 µmol/L), and in any event did not contribute to the newborn BA pool. No apparent side-effects of the maternal UDCA treatment were observed in any newborn infant, and no deterioration in postnatal development was observed during the routine 1-year follow-ups. Therapeutic administration of UDCA during lactation is safe for breastfed babies since UDCA only gets into breast milk in negligible amounts. UDCA treatment should be allowed and included into the guidelines for the therapy of cholestatic diseases in breastfeeding mothers.

Influence of the secondary deployment of expanded polytetrafluoroethylene-covered stent grafts on maintenance of transjugular intrahepatic portosystemic shunt patency.

PURPOSE: To evaluate the effects of secondary deployment of expanded polytetrafluoroethylene (ePTFE)-covered stent grafts in the treatment of dysfunctional transjugular intrahepatic portosystemic shunts (TIPSs) in comparison with other common approaches (conventional angioplasty or implantation of bare metal stents). MATERIALS AND METHODS: A retrospective review of 121 dysfunctional bare metal TIPS presenting between 2000 and 2004 was conducted. The group was divided into four subgroups according to the type of intervention: conventional angioplasty (52 cases; 43%), bare metal stent deployment (35 cases; 28.9%), nondedicated ePTFE-covered stent-graft deployment (15 cases; 12.4%), and dedicated ePTFE-covered stent-graft deployment (19 cases; 15.7%). In all four groups, the primary patency after the specific intervention was calculated and mutually compared. RESULTS: Primary patency rates after 12 and 24 months were 49.7% and 25.3%, respectively, in conventional angioplasty; 74.9% and 64.9%, respectively, with bare metal stents; 75.2% and 64.5%, respectively, with nondedicated ePTFE-covered stent grafts; and 88.1% and 80.8%, respectively, with dedicated ePTFE-covered stent grafts. CONCLUSIONS: In the treatment of dysfunctional TIPS, better patency after the intervention was obtained by deploying dedicated ePTFE-covered stent grafts in comparison with conventional angioplasty, bare metal stents, and nondedicated ePTFE-covered stents.

TIPS creation in patients with persistent left superior vena cava.

Transjugular intrahepatic portosystemic shunt is a minimally invasive endovascular procedure that has played an important role in the treatment of acute or repeated variceal bleeding or refractory ascites. The standard venous access route for this procedure is the right jugular vein. Sometimes it is better to use the left jugular vein because of lower probability of life threatening complication or technical failure. In this case reports the authors have described their experience with TIPS creation in two patients with persistent left and absent right superior vena cava and recommend using the left jugular vein as an access route in this rare anatomical variant.

The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites--a randomized multicentric study.

BACKGROUND/AIMS: Postparacentesis circulatory dysfunction is the most severe complication of ascites paracentesis. The aim of our study was to compare the standard treatment with the administration of a vasoconstrictor terlipressin. METHODOLOGY: Forty-nine patients treated by paracentesis due to tense ascites were randomized for the treatment with albumin (8g/L of removed ascites) or terlipressin (1 mg every four hours for 48 hours). The blood pressure, heart rate, diuresis, electrocardiograph, standard biochemical and hematological parameters, sodium, potassium and nitrogen urinary excretion, aldosterone and renin activity in the blood plasma were monitored for a period of 72 hours. RESULTS: In any parameter of hemodynamic changes, no statistically significant difference was demonstrated between randomized groups, in particular measurements as well as in the development in the course of the first three days after the intervention. The result suggests similar efficacy of the circulatory dysfunction prevention after the paracentesis in both treatment procedures. In both groups, on the first three days, there was a tendency to improve hemodynamics reflected by the renin-angiotensin-aldosteron system activity. In the terlipressin group, this tendency approached statistically significant levels. CONCLUSIONS: The administration of terlipressin in a dose of 1 mg every fourth hour performed for a period of 48 hours was as effective as intravenous albumin in preventing hemodynamic changes in patients with tense ascites treated by paracentesis. The treatment was well tolerated.

Intraluminal high dose rate brachytherapy of tumorous esophageal stenoses.

BACKGROUND/AIMS: The prognosis of inoperable carcinomas of esophagus is poor, and therapeutic efforts are generally limited to palliation. The aim of this study was to retrospectively evaluate the effectiveness of intraluminal high dose rate brachytherapy in the palliative treatment of tumorous esophageal stenoses. METHODOLOGY: Between February 1997 and July 2002 intraluminal brachytherapy was performed in 19 patients with inoperable esophageal carcinoma (squamous cell carcinoma in 14 cases and adenocarcinoma in 5 cases). All patients had dysphagia at presentation. Brachytherapy was performed using high dose rate afterloading system. RESULTS: Dysphagia was improved in all patients. The mean survival was 248 days. No mechanical complications were observed during introduction of the applicator. CONCLUSIONS: Our experience indicates that intraluminal brachytherapy is an effective and safe method of palliation of dysphagia caused by malignant esophageal stenosis.

Diagnosis, etiology and management of the Budd-Chiari Syndrome: a bloodcoagulation and hepatological study on the course of the disease treated with TIPS.

BACKGROUND: Budd-Chiari Syndrome (BCS) is characterized by obstruction of blood flow in hepatic veins. The aim of the study was to analyze diagnosis, etiology and management of BCS. METHODS: We analyzed 44 patients (32 females, 12 males, the mean age <35y of age) treated with TIPS. Ascites was found in 35 patients as the most frequent symptom. The median of total follow-up was 52 months. Non-covered (bare) or covered stent was inserted to all patients. Diagnosis of myeloproliferative neoplasm (MPN) was based on WHO criteria. Other inherited or acquired thrombophilia were assessed as well. Therapy of BCS was with regard to the etiology. RESULTS: The etiology of BCS was identified in 38 cases. Ph- MPN was found as the most common risk factor (50%, N.=22), especially polycythemia vera. JAK2V617F mutation was detected in the most of 22 MPN cases (82.5%). The second most common etiologic factor was inherited thrombophilia (18%, N.=8). In the non-covered (bare) stent group, a primary patency rates 52.9% in 1 year and 20% in 5 years after TIPS (Portasystemic Shunt, Transjugular Intrahepatic) creation. In the covered stent group the 1-year and 5-year primary patency rates were was 80% and 33.3% respectively. The average 5-year re-intervention rate per patient was 1.65 procedures in the bare stent group and 0.67 in the covered stent group. Re-interventions were more frequent in MPN patients. All patients were anticoagulated with heparin at the beginning, switched to vitamin K antagonist. On top of TIPS, anticoagulant and a vigorous therapy of underlying disorder are necessary. CONCLUSION: BCS is a serious and life-threatening disorder in MPD is a major cause of morbidity and mortality. Therapy requires a multidisciplinary approach. Insertion of TIPS dedicated covered stent is a very effective treatment in cases resistant to conservative approach with lower dysfunction rate and the number of re-interventions.

Glycogen phosphorylase BB levels are associated with haemodynamic parameters in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt insertion.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess glycogen phosphorylase BB (GPBB) concentration in relation to echocardiographic and haemodynamic parameters in patients before and after TIPS insertion. METHODS: The study population consisted of 55 patients (38 men and 17 women, age 55.6±8.9 years, range 37-74 years) with liver cirrhosis treated with transjugular portosystemic shunting. GPBB, echocardiographic, and haemodynamic parameters were measured before TIPS insertion and 24 h after the procedure. GPBB concentrations were assessed using the Cardiac Array for Evidence Investigator protein biochip. Correlation between parameters was assessed using the Spearman's coefficient. RESULTS: Serum post-procedural GPBB concentrations were increased in comparison with baseline (5.58 vs. 2.67 µg/L, P<0.001). GPBB concentration after TIPS significantly correlated with baseline systemic vascular resistence (r=0.330; P=0.017) and cardiac index (r=0.313; P=0.025). CONCLUSION: GPBB concentration measurement may be a useful tool for monitoring myocardial ischemia during a TIPS procedure.

Indel in the FIC1/ATP8B1 gene-a novel rare type of mutation associated with benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare inherited liver disease characterized by recurrent attacks of severe cholestasis with no progression to end stage liver disease. Patients have jaundice, however, serum gamma-glutamyltransferase and cholesterol levels remain within the normal range during the attacks. Three mutations in the familial intrahepatic cholestasis 1 (ATP8B1) gene encoding a P-type ATPase have been reported so far in patients with the autosomal recessive form of BRIC. A novel rare type insertion-deletion mutation, also called indel, was found in exon 24 of ATP8B1 in our patient together with a known missense mutation 1982T>C in exon 17. The mechanism of the indel formation is proposed and impact of the indel mutation on the function of ATP8B1 protein is discussed.

Transjugular intrahepatic portosystemic shunt in five children with cystic fibrosis: long-term results.

BACKGROUND/AIMS: The aim of this study was to report results of TIPS (transjugular intrahepatic portosystemic shunt) in 5 consecutive children with cystic fibrosis and monitor long-term follow-up results. METHODOLOGY: Five cystic fibrosis patients with multinodular cirrhosis of the liver and complications of portal hypertension (repeated variceal bleeding refractory to endoscopic treatment) underwent TIPS creation. There were 3 males and 2 females aged 8 to 18 years (median 14 yrs), their weight range was 27-51 (median 40) kg. A routine TIPS technique was used. The patients were followed by ultrasonography. RESULTS: The TIPS was successfully performed in all five patients. The mean portosystemic pressure gradient was reduced from 17 to 10 mmHg. There were no deaths related to the procedure. No clinical or laboratory signs of bleeding into the gastrointestinal tract were observed in any patient within the first 30 days following TIPS. There was recurrent bleeding 6 times and asymptomatic stenoses were revealed by ultrasonography 15 times during a follow-up period of 15-81 (median 70) months. All stenoses were successfully dilated. One patient had liver transplantation 15 months after TIPS. Two patients died 6.7 years and 4.5 years following the placement of TIPS due to respiratory insufficiency. CONCLUSIONS: Symptomatic portal hypertension was successfully managed with TIPS in long-term follow-up; multiple reinterventions were required for shunt stenoses. TIPS served as a bridge to liver transplantation in one case.

Transduodenal intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region.

BACKGROUND/AIMS: The prognosis of carcinomas of the subhepatic region is poor, and therapeutic efforts are limited mostly to palliation. The aim of this study was to retrospectively evaluate the effectiveness of transduodenal administration of intraluminal high dose rate brachytherapy in the palliative treatment of bile duct and pancreatic head carcinomas. METHODOLOGY: Twelve patients with inoperable bile duct and pancreatic head carcinomas were treated by transduodenal brachytherapy using high dose rate remote afterloading system. Eleven patients were treated by intraluminal brachytherapy inserted via a nasobiliary drain and one patient by intraluminal brachytherapy via a nasopancreatic drain inserted in the duct of Wirsung. RESULTS: After transduodenal intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated with the mean survival of 284 days. CONCLUSIONS: Transduodenal intraluminal brachytherapy is technically feasible. The addition of intraluminal brachytherapy may be beneficial to patients in whom drainage can be established. Transduodenal insertion of brachytherapy is not competitive to the percutaneous approach but spreads the possibilities of the treatment of bile duct carcinoma. Intraluminal brachytherapy of pancreatic head carcinoma is feasible only via transduodenal approach.

[Congenital dyserythropoietic anemia--type II (CDA-II) in 3 siblings with long-term follow up and iron overload]. / Kongenitální dyserytropoetická anémie-typ II (CDA-II) u trí sourozencu s dlouhodobým sledováním a pretízením zelezem.

The diagnosis of congenital dyserythropioetic anemia-type II (CDA-II) was established in 1974 in three siblings aged 20, 18 and 5 years, respectively. Liver biopsy performed in two elder siblings on admission revealed liver siderosis. Anemia showing haemolytic component with destruction of erythrocytes in the spleen was corrected after splenectomy. Increased number of erythrocytes showing "the double membrane phenomenon" was found in the peripheral blood after splenectomy. All three siblings developed cholecystolithiasis with choledocholithiasis and obstructive jaundice in two of them. Two patients at the age of 49 and 34 years (the third died in an accident at the age of 40 years) developed 29 years after the diagnosis of CDA-II had been established signs of iron overload with transferin saturation 99%, serum ferritin 1450.4 microg/l and 1131.7 microg/l respectively, and hepatic iron concentration (dry weight) 14,843 microg/g and 15,415 microg/g (norm 70-1400 microg/g) respectively. No mutations of HFE gene (C282Y and H63D) were found. Liver biopsy showed heavy accumulation of hemosiderin in hepatocytes and reticuloendothelial cells. The structure of the liver tissue was not changed, only mild fibrosis in portal area was present in the older patient. Because of iron overload therapy with phlebotomy once monthly (400 ml) has been started in both patients. In peripheral blood films excess of Pappenheimer bodies was found.

Elevated cardiac markers are associated with higher mortality in patients after transjugular intrahepatic portosystemic shunt insertion.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPSs) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess the value of cardiac markers before and after TIPS insertion for the prediction of one-year mortality in cirrhotic patients. METHODS: The study population consisted of 55 patients (38 men and 17 women, aged 55.6 ± 8.9 y, range 37-74) with liver cirrhosis treated with transjugular portosystemic shunting. Biochemical markers were measured before and 24 h after TIPS. High-sensitivity cardiac troponin T (hs-cTnT) was tested by high-sensitivity immunoassay for Elecsys analyser (Roche Diagnostics). Concentrations of creatine kinase MB isoenzyme, myoglobin (MYO), glycogenphosphorylase BB isoenzyme (GPBB) and heart type of fatty acid binding protein (FABP) were measured by the Evidence Investigator protein biochip system (Randox Laboratories). RESULTS: In patients before TIPS insertion, hs-cTnT was increased above the cut-off (0.014 µg/L) in 39.2% of patients. Higher hs-cTnT and FABP concentrations were associated with poor survival in patients before TIPS (hs-cTnT: P = 0.018; FABP: P = 0.016). Twenty-four hours after the TIPS procedure, we found a significant elevation in serum GPBB in comparison with preprocedural values (P < 0.001). There was an association between postprocedural concentrations of cardiac markers (MYO, hs-cTnT, FABP) and overall survival. CONCLUSIONS: Measurement of cardiac markers, mainly hs-cTnT and FABP, may be useful for mortality prediction in cirrhotic patients after TIPS. Cardiac markers are better mortality predictors than other risk factors such as age, gender or Child-Pugh score.

Observational Cohort Study of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Abstract: Introduction and aim. Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. Material and methods. A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher’s exact test, χ2, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. Results. 257 (37.9%) patients developed HE after TIPS. Patients’ age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. Conclusion. We have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.