Assessment of methotrexate hepatotoxicity in psoriasis patients: a prospective evaluation of four serum fibrosis markers.

BACKGROUND: Low-dose oral methotrexate (MTX) is an effective immunosuppressive therapy for chronic plaque psoriasis. However, its use is hampered by the risk of liver fibrosis. AIM: To compare the results of serial measurements of serum fibrosis markers during the remission-induction phase of treatment with MTX to those of patients on biological therapy and long-term MTX therapy (>2 years). SUBJECTS AND METHODS: Serum concentrations of hyaluronic acid, N-terminal propeptide of collagen type III (PIIINP) and the results of two multi-test algorithms Fibrotest and Hepascore were evaluated in patients with chronic plaque psoriasis (N = 24, age: 28-79 years, baseline Psoriasis Area Severity Index PASI 13.5, range 2.2-33) at baseline and weeks 16 and 26 after the start of pharmacokinetically guided therapy with MTX (Group A). Patients on established therapy with biologics (N = 15, Group B) and long-term MTX users (N = 10, Group C) with the mean baseline PASI scores of 0.9 and 1.2 were studied in parallel cohorts. RESULTS: At baseline, HA, Hepascore and PIIINP were correlated with PASI of Group A patients. At weeks 16 and 26, HA decreased by 48% and 40% (P < 0.001) and Hepascore by 31 (P < 0.01) and 20% (P < 0.05) respectively. PASI75 (≥ 75% improvement from baseline PASI) was observed in 76% of Group A patients by week 26 and the absolute decreases in PASI and both fibrosis markers were correlated (HA: r = 0.49, P = 0.018, Hepascore: r = 0.47, P = 0.022). In contrast, no significant within-group differences were found in HA and Hepascore results of patients in the groups B and C. PIIINP and Fibrotest were stable in all groups. CONCLUSION: The fibrosis markers hyaluronic acid and Hepascore (the multiple test algorithm which includes hyaluronic acid) are less liver specific and more prone to reflect psoriasis activity than PIIINP and Fibrotest.

[Steatosis and steatohepatitis in diabetic patient]. / Steatóza a steatohepatitida u diabetika.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition of excess fat deposition within the liver. NAFLD includes a spectrum of liver pathology ranging from bland hepatic steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrosing condition of the liver thought to be an intermediate stage of NAFLD that may progress to endstage liver disease, liver-related death and hepatocellular carcinoma. Nonalcoholic steatohepatitis (NASH) is a common liver disease that is characterized histologically by hepatic steatosis, lobular inflammation, and hepatocellular ballooning, it can progress to cirrhosis in up to 15% of patients. There is currently no therapy that is of proven benefit for nonalcoholic steatohepatitis. The disease is closely associated with insulin resistance and features of the metabolic syndrome such as obesity (increased waist circumference), hypertriglyceridemia, and type 2 diabetes. The pathologic criteria are now well established and the diagnosis can only be made once the absence or limited use of alcohol is confirmed. In addition to insulin resistance, oxidative stress has been implicated as a key factor contributing to hepatic injury in patients with nonalcoholic steatohepatitis. Thus, both insulin resistance and oxidative stress are attractive targets for therapy in patients with this disease. Several pilot studies have provided evidence that insulin sensitizers such as thiazolidinediones and antioxidants such as vitamin E improve clinical and histologic features of nonalcoholic steatohepatitis. The medical evidence of a benefit, however, is limited, because these studies had small samples and were performed at single centers. Moreover, a recent multicenter trial showed a reduction in hepatic steatosis but no improvement in markers of cell injury after a year of rosiglitazone therapy. The value of these remains uncertain. Until now the best trial was done by Sanyal, who studied 240 patients divided into 3 groups (pioglitazone versus vitamin E versus placebo)--multicenter, randomized, double-blind clinical trial in non-diabetics.

[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.

[Metabolic syndrome and the liver (NAFLD/NASH)]. / Metabolický syndrom a játra (NAFlD/NASH).

Metabolic syndrome (MS) is one of the most prevalent disease states in the so-called developed countries and is closely associated with the incidence of cardiovascular as well as other diseases. Predominant sign is the abdominal type of obesity with increased visceral fat mass and the associated insulin resistance. Glucose metabolism disorder, dyslipidemia and arterial hypertension are other important attributes. Metabolic syndrome is also closely associated with the liver steatosis, mostly benign and reversible liver disease. Nevertheless, uncomplicated steatosis may, under certain conditions, progress to inflammation and the disease may, through the stage of NASH (nonalcoholic steatohepatitis) and liver fibrosis, result in liver cirrhosis and hepatocellular carcinoma. Anglo-Saxon literature uses the term NAFLD (non-alcoholic fatty liver disease) to refer to these various stages ofthe liver disease (uncomplicated liver steatosis, steatohepatitis, fibrosis and cirrhosis). While simple steatosis is not dangerous for the patient, NASH is the sign of developing cirrhosis. Etiopathogenesis of NASH features identical characteristics as etiopathogenesis of insulin resistance and metabolic syndrome. Even though liver biopsy remains the gold standard in the diagnosis, new diagnostic approaches are emerging that could be useful in distinguishing simple steatosis from NASH. Therapy includes lifestyle changes, insulin resistance-reducing medication (also useful in the treatment of type 2 diabetes) with a range of other agents under development. In the meantime, randomized double-blind placebo-controlled studies with histological proof of the results are still lacking. A range of unresolved issues remains with regards to etiopathogenesis as well as diagnosis and treatment of NAFLD and NASH.

Hiatal hernia and Barrett's oesophagus impact on symptoms occurrence and complications.

UNLABELLED: The aim of the study was to evaluate the influence of sliding hiatal hernia over the Barrett's oesophagus, including symptoms rate and complications. METHODS: A total of 520 (4.6%) cases of Barrett's oesophagus were found out of 18.276 upper gastrointestinal endoscopies, performed in 11.276 patients at a single tertiary centre in a period from 1994 to 2004. RESULTS: Sliding hiatal hernia was found in 58% of patients with Barrett's oesophagus, more frequently in men (60%). The association between hernia and some complications of Barrett's oesophagus was significant (94% of Barrett's ulcer, 77% of low-grade dysplasia with p < 0.01). However, there was no significant association with adenocarcinoma (54%; p > 0.05). The other complications of Barrett's oesophagus (i.e. bleeding, stenosis, high-grade dysplasia) were identified in small number (less than 10), so they were not evaluated statistically. Association between the presence of hiatal hernia and occurrence of symptoms (reflux symptoms, dysphagia, odynophagia, dyspeptic and other symptoms) was significant with p < 0.01. CONCLUSIONS: Our study suggests that sliding hiatal hernia may play a significant role as a pathophysiologic factor in Barrett's oesophagus. Complications rate of Barrett's oesophagus were not equally frequent in particular cases with hiatal hernia. The occurrence of symptoms is getting more pronounced in those with sliding hiatal hernia.

[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.

[Diagnosis and treatment of chronic hepatitis B. Recommendations of the Czech Hepatology Society of the J. E. Purkinje Medical Society and the Society of Infectious Medicine of the J.E. Purkinje Medical Society]. / Diagnostika a lécba chronické hepatitidy B.

Chronic hepatitis B is one of the world's most common infectious diseases. In the Czech Republic it has a prevalence of 0.56%. Antiviral therapy for chronic hepatitis B demonstrably increases quality of life and where indication criteria are met and standard therapeutic procedures are followed, it is clearly cheaper than treatment for the complications of advanced cirrhosis of the liver or hepatocellular carcinoma. At the time of issuing of this recommendation, 4 medicines were classified for the treatment of chronic hepatitis B in the Czech Republic--pegylated interferon (IFN) alpha-2a, conventional IFN alpha, lamivudine (LAM) and adefovir dipivoxil (ADV). In a number of other developed states, entecavir (ETV) and telbivudine (LdT) have also been approved for treatment. The most effective treatment available at present is pegylated IFN alpha-2a, which should be the medication of first choice for initial treatment of hepatitis B, HBeAg positive and negative forms, provided that there are no contraindications for IFN alpha treatment. Conventional (standard, classical) IFN alpha can also be used, though clinical studies have shown it to be less effective than pegylated IFN alpha-2a. The main advantage of interferon compared to other commercially available medications is its relatively shorter and more clearly defined treatment period, the high probability of permanent suppression of virus replication and seroconversion of HBeAg/anti-HBe (in HBeAg positive forms of the illness) and the non-creation of mutant strains of HBV resistant to IFN in the course of treatment. If there are contraindications for IFN alpha (pegylated or conventional) or it is ineffective or poorly tolerated, ADV, ETV, LAM or LdT can be used. LAM and LdT treatments are often accompanied by the appearance of mutant strains of HBV, that are resistant to lamivudine or LdT and therefore they are not preferred.

[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.

A double-blind dose-escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis.

BACKGROUND: Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations. AIM: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups. METHODS: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g. RESULTS: The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients. CONCLUSIONS: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.

[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.

[The Budd-Chiari syndrome in a patient with primary thrombocythemia treated with interferon alfa and transjugular portosystemic shunt]. / Budduv-Chiariho syndrom u pacientky s primární trombocytémií lécené interferonem alfa resený transjugulární portosystémovou spojkou.

The case report of a young female patient with personal history of primary thrombocythaemia, treated with interferon alpha, admitted to our medical department for severe abdominal pain, hepatomegaly, ascites and alteration of hepatic function is presented. Magnetic resonance imaging showed the picture typical for Budd-Chiari syndrome caused by external obstruction of the intrahepatal portion of inferior vena cava. The cause of the syndrome remains uncertain, possibility of the haematogenic infiltration of the liver or venal thrombosis within primary or secondary (interferon-induced) antiphospholipid syndrome is discussed. Liver biopsy could elucidate the exact cause, but it was not performed for technical problems.

[Intravascular brachytherapy in the prevention of vascular restenosis]. / Intravaskulární brachyterapie v prevenci cévních restenóz.

Vascular restenoses currently represent a major problem in the treatment of vascular stenoses. One of new approaches in the prevention of restenoses is intravascular brachytherapy. Intravascular brachytherapy uses local irradiation of the stenotic vessel segment by ionizing radiation with the aim of prevention of restenosis. This is a new rapidly developing multidisciplinary approach based on collaboration of specialties of intervention radiology, intervention cardiology, angiology, nephrology and radiation oncology. This review examines current options of intravascular brachytherapy as well as results of clinical trials evaluating the efficacy of intravascular brachytherapy in the different anatomical regions. Intravascular brachytherapy may substantially reduce the rate of restenoses. However, intravascular brachytherapy should be currently used only in the setting of clinical trials. Optimal method of irradiation of the stenotic segment of the vessel is still to be defined.