Manganese and copper levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis.

The liver and the biliary tree form the main excretory route of manganese (Mn) and copper (Cu). Cholestasis, can lead to the accumulation of these trace elements in the organism, resulting in toxicity to the basal ganglia of the central nervous system. The aim of our study was to reveal the influence of long-term cholestasis on the Mn and Cu levels in the blood of patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We recruited patients with PBC (n = 20) and PSC (n = 32). A control group (n = 40) was also set up. We also examined serum bile acid concentrations and liver enzyme activities. We did not observe any significant differences in any of these parameters between the PBC and PSC groups. The Mn and Cu levels in the PBC and PSC patients differed significantly from the that in the control group (p < 0.0001 and p < .021, respectively). Patients in whom the laboratory cholestasis markers normalized during ursodeoxycholic acid treatment (18/52;35%) presented with significantly lower levels of Mn and Cu (p = .015 and p = .012, respectively). Ten PSC patients showed normal levels of Mn and Cu six months after liver transplantation. Fine tremors, rigidity, dysarthria, and hypomimia were reported in nine (23%), eight (20%), four (10%), and eight (20%) patients, respectively. In addition to monitoring the cholestasis levels, liver function, and Mn and Cu levels during the long-term treatment of PBC and PSC patients, it is important to also regularly monitor the occurrence and development of extrapyramidal symptoms of Parkinson's-like syndromes.

Liver transplantation as potential curative method in severe hemophilia A: case report and literature review.

The authors present clinical case of orthotopic liver transplantation for cirhosis due to chronic viral hepatitis C in a subject with severe hemophilia A. Preoperatively performed pharmacokinetic study with recombinant F VIII confirmed satisfactory in vivo recovery of 2.1 %. A bolus application of 52 units F VIII/kg body weight with target F VIII activity over 100.0 % was administred shortly before the transplantation started. Totally, 30 000 units of recombinant F VIII, 3 thrombocyte concentrates, 2 erythrocyte concentrates, 5 units of virally inactivated plasma, 1 unit of fresh frozen plasma and 3 500 antithrombin units were used. There were no perioperative or postoperative bleeding complications, F VIII substitution was stopped on postoperative day 3. The patient was discharged on twentieth postoperative day.

Use of idarucizumab in clinical practice: a case report.

Budd-Chiari syndrome is a serious condition which in chronic course leads to the development of liver cirrhosis. Anti-coagulant treatment of this syndrome is fully indicated and in the treatment can be used dabigatran. Advanced cirrhosis of the liver due to this disease can be an indication for a liver transplant. In this case, it is a great advantage the existence of an antidote to dabigatran (idarucizumab) in order to adjust the coagulation ratios and prevent bleeding disorders. Referred to a case report describes the first experience with idarucizumab in context with liver transplant in a patient with Budd-Chiari syndrome.

[First experience with elbasvir/grazoprevir fixed-dose combination in real-life practice in the Czech Republic].

Hepatitis C virus infection (HCV) is one of the leading causes of chronic liver disease worldwide. The new fixed-dose combination of the highly potent second wave first generation NS5A inhibitor elbasvir (50 mg) and the second generation protease inhibitor grazoprevir (100 mg) is contained in the drug Zepatier. This combination is indicated for the treatment of patients chronically infected with HCV genotypes 1 or 4. Between June and August 2017, the treatment was initiated in 22 patients with chronic viral hepatitis C, with 17 patients being treated in the Department of Infectious Diseases University Hospital Brno and five patients in the Center of Cardiovascular and Transplant Surgery in Brno. All patients were infected with HCV subtype 1b. In all cases, the duration of Zepatier monotherapy (without simultaneous ribavirin administration) was 12 weeks. At the moment, only preliminary results are available. All 22 patients achieved end-of-treatment virologic response. In nine patients, it was already possible to evaluate the virologic response at four weeks after the end of treatment, with sustained virological response (SVR12) was observed in all these patients. The most common complaints were fatigue (3 patients, 14 %) and headache (2.9 %). These problems were not serious and did not interfere with normal daily activities of treated persons.

[Viral hepatitis C and organ transplantation]. / Virová hepatitida C a transplantace orgánu.

At the Centre for Cardiovascular and Transplantation Surgery, Brno (CKTCH), a total of 638 liver transplantations were performed from the beginning of the transplantation programme on 2/2 1983 to 1/1 2017. Of the overall number of 638 transplantations indicated based on cirrhosis with chronic hepatitis C (HCV), 68 patients (11 %) underwent liver transplantation. Patients with HCV diagnosis were treated both while on the waiting list and after liver transplantation (LT). There was interferon as well as interferon-free therapy used during the treatment. 15 patients received interferon therapy after LT with only 2 of them achieving a sustained virological response 2/15 (13 %). 28 patients received interferon-free therapy after LT. A sustained virological response (SVR 12) was reached by 26/28 (93 %) patients.Key words: liver transplantation - viral hepatitis C.

[Infectious complications related to liver transplants]. / Infekcní komplikace u transplantací jater.

Infection is a feared complication in the process of transplantation. The study discusses sources of infection, screening of infection and risk factors for infection, time occurrence of individual infections during the peritransplantation and posttransplantation course. It describes the most frequent forms of bacterial, viral and mycotic infections. It specifies efficient prophylactic measures that considerably reduce the risk of infection following liver transplantation.Key words: bacterial infection - cytomegalovirus (CMV) - EB virus (EBV) - hepatitis B (HBV) - hepatitis C (HCV) - liver transplantation - mycotic infection prophylaxis - risk factors - viral infection.

[Real data o viral hepatitis C therapy in the Czech Republic]. / Reálná data lécby virové hepatitidy C v Ceské republice.

We reported the first real data about efficacy of interferon-free therapy of chronic hepatitis C in the Czech Republic. Patients were treated with combined therapy of paritaprevir/ritonavir + ombitasvir + dasabuvir with or without ribavirin. There were 109 patients, predominantly men - 62 (57 %), most of them infected by genotype 1b - 101 patients (93 %), minority infected by genotypes 1a (6/109, 5 %) and 4 (2/109, 2 %). Both treatment-naive (43/109, 39 %), and treatment-experienced patients (66/109, 61 %) were treated. Sustained virological response 12 weeks after therapy termination (SVR12) was 100 %, with exclusion of patients with other reason than virological treatment failure.Key words: dasabuvir - chronic hepatitis C - ombitasvir - paritaprevir/rinonavir - ribavirin.

[Tumours and liver transplants]. / Tumory a transplantace jater.

Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one.

Transjugular Intrahepatic Portosystemic Shunt in Liver Transplant Recipients: Outcomes in Six Adult Patients.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is regularly used in treatment of clinically significant portal hypertension. Liver transplant recipients are, however, rarely indicated for the procedure. The study retrospectively examines the results of TIPS placement in 6 patients after OLT. METHODS: 4 males and 2 females (aged 36 to 62 years), treated with TIPS between 2007 a 2018, were included in the study. 5 patients had previously undergone liver transplantation for liver graft cirrhosis, 1 patient for Budd-Chiari syndrome. The piggyback caval reconstruction technique was selected in 4/6 cases. PH developed after OLT due to the recurrence of underlying liver condition and sinusoidal obstruction syndrome in half of the cases, respectively. Indications for TIPS were refractory ascites in 4 cases and variceal bleeding in 2 cases. RESULTS: Standard TIPS technique was used and technical success was achieved in all cases with a procedure-related complication in 1 patient. One patient died shortly after TIPS placement. The remaining patients all reported regression of clinically significant PH. Late complications appeared in 2 patients. Liver retransplantation after TIPS creation was performed in 1 case. Median TIPS patency was 55 months. 2/6 patient continue to thrive with a patent shunt. CONCLUSIONS: Transjugular intrahepatic portosystemic shunt in OLT recipients is technically feasible. Favorable clinical outcomes were reported particularly in patients treated for sinusoidal obstruction syndrome who were indicated to TIPS for refractory ascites.

Immunoglobulin G4-related cholangitis: a variant of IgG4-related systemic disease.

IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of 'sclerosing cholangitis'. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver - a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the first-choice therapy of IgG4-related sclerosing cholangitis. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10-30% of patients with PSC.

Hepatitis E - epidemiology and clinical course in the largest cohort in the Czech Republic.

Introduction: The majority of hepatitis E (HE) reports come from Western Europe. The aim of the study was to describe the typical epidemiological and clinical characteristics of HE in the Czech Republic. Methods: A retrospective analysis of 173 patients with HE. Results: At least 90% of cases were autochthonous (HEV-3 genotype). Seventeen patients were treated with ribavirin. Five underwent liver transplants because of fulminant HE. We noted neurological symptomatology in 9 cases. Six patients developed chronic HE. Conclusions: There is a possibility of severe health complications caused by the hepatitis E virus in the Czech Republic.

[Efficacy of pegylated interferon alpha-2a and ribavirin treatment in chronic hepatitis C patients depends on various baseline parameters and early viral kinetics]. / Závislost úcinnosti lécby chronické hepatitidy C pegylovaným interferonem alfa-2a a ribavirinem na v stupních parametrech a virové kinetice v pocátcích lécby.

OBJECTIVE: The aim of the study was to compare efficacy and viral kinetics during antiviral treatment in different chronic hepatitis C patients--naïve, relapsers and non-responders to previous pegylated interferon alpha (PEG-IFN) and ribavirin treatment, with different genotypes, baseline viremia, body weight, age and gender--and to find some baseline parameters which can predict Sustained Virological Response (SVR; negative serum HCV RNA 24 weeks after treatment). MATERIAL AND METHODS: 216 chronic hepatitis C patients were treated with PEG-IFN alpha-2a 180 mg/wk and ribavirin 1 000 or 1 200 mg/day. There were 140 men and 76 women, mean age 40, range 19-70 years; 142 (66 %) naïve, 37 (17 %) relapsers after previous PEG-IFN and ribavirin treatment, and 37 (17 %) non-responders to this treatment. 172 (79,6%) has genotype 1 infection, 4 (1,9 %) genotype 2, 34 (15,6 %) genotype 3, 1 (0,5 %) genotype 4 or 6 infection, and 4 (1,9 %) were infected by unknown viral genotype. Quantitative detection of HCV RNA was done at baseline (216 pts.), 24 hours (83 pts.), 14 days (85 pts.), 28 days (88 pts.), and 84 days (211 pts.) after the first dose of PEG-IFN. RESULTS: 195 patients have completed the treatment period and 179 patients the 24-week follow-up period. The probability of SVR was significantly higher (P < 0,001) in naïve patients (74/114, 64,9 %) and relapsers (22/30, 73,3 %) than in non-responders (9/35, 25,7 %) and in genotype 3 patients (23/28, 82,1%) than genotype 1 patient (77/143, 53,8 %) (P = 0,002). The patients with SVR comparing those without SVR have significantly lower weight (mean 72,8 kg vs. 79,1, P = 0,008(, were younger (mean 36,2, vs. 45,5, P > 0,001), and had lower baseline viremia (mean 1,014 3 106 IU/mL vs. 2,415 3 106 IU/mL, P > 0,001). SVR was more frequent in women than in men (43/63, 62,8 % vs. 62/116, 53,4 %) but difference was not significant (P = 0,059). Undetectable serum HCV RNA at week 12 was more predictive of SVR than early viral response (minimum 2 log decrease of serum HCV RNA during the first 12 weeks of treatment)--98/122 (80,3 %) versus 104/141 (73,1 %) of SVR. CONCLUSIONS: 1) The monitoring of viral kinetics during first 12 weeks of antiviral therapy in hepatitis C patients was an important predictive value for SVR. 2) Negative serum HCV RNA at week 12 was more predictive of SVR than early viral response. 3) The probability of SVR was significantly higher in patients with lower baseline viremia, body weight and younger adults. 4) Gender was not significant for the efficacy of treatment.

Factors participating in the development and mortality of variceal bleeding in portal hypertension--possible effects of the kidney damage and malnutrition.

BACKGROUND/AIMS: Acute bleeding from esophageal varices due to portal hypertension is a frequent and severe complication of liver cirrhosis. The development of esophageal varices as well as their rupture depends on the level of portal pressure; however, a number of other factors may play a negative role in the rise of bleeding and its prognosis. METHODOLOGY: The report presented has compared a set of 46 patients admitted to hospital for acute bleeding with 48 cirrhotics hospitalized for other reasons. RESULTS: Bleeding patients had significantly higher level of nitrogenous substances (urea 14.1 mmol/L vs. 7.78 mmol/L, p < 0.01, creatinine 129.8 micromol/L vs. 106.04 micromol/L; p = 0.09). The disturbed renal function in itself probably does not increase the risk of bleeding, it may be rather considered a certain prognostic index of the portal hypertension degree. Bleeding patients had a lower level of total protein (60.7 g/L vs. 69.9 g/L; p < 0.01) with only slight insignificant decrease of albumin (26.64 g/L vs. 28.51 g/L). Cirrhotic patients are known to suffer from malnutrition and it is possible that malnutrition shares negatively and directly in the rise of bleeding. CONCLUSIONS: A prognostic index of mortality was a more conspicuous disorder of hepatic function (bilirubin 97.4 micromol/L vs. 57.4 micromol/L; p = 0.1; prolonged prothrombin time 1.99 INR vs. 1.56 INR; p = 0.01) and again the disorder of renal function (creatinine 166.7 micromol/L vs. 114.9 micromol/L; p = 0.09). Therefore, the maintenance of good renal function must be a component of complex therapy given to bleeding patients.

Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.

OBJECTIVE: To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics. METHODS: Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated. RESULTS: The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics. CONCLUSION: Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.

Spontaneous bacterial peritonitis in the Czech Republic: prevalence and aetiology.

The aim of the study was to determine the prevalence and detailed data concerning the incidence of spontaneous bacterial peritonitis in the Czech Republic. Ninety-nine patients with liver cirrhosis and ascites were examined. Spontaneous bacterial peritonitis was diagnosed in 35 patients (35.4%). It was revealed more often in patients with alcoholic aetiology of cirrhosis whose anamnesis involved sub-febrile or febrile states and the deterioration of ascites. Elevated serum leucocyte counts and increased levels of C-reactive protein can contribute to the diagnosis. A low level of total protein and albumin in ascites predisposes to the increase of this infection. The reduction of the platelet count in a set of patients with spontaneous bacterial peritonitis indicates the influence of portal hypertension in the aetiology of the disease.

Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis B.

Sarcoidosis is one of the possible rare complications of interferon-alpha (IFN-alpha) therapy. Only a few reports have been published on this disease, and these have been associated with the treatment of malignant diseases, essential thrombocytosis, and chronic hepatitis C. We report on a 64-year-old man with chronic hepatitis B (HBsAg, HBeAg, HBV DNA-positive) who was treated with recombinant IFN-alpha-2b (5 MU three times weekly) for 28 weeks. Tolerance to treatment was very good; only a mild flu-like syndrome appeared. Twelve months after completing the therapy, a chest X-ray was performed that revealed bilateral hilar masses, and high-resolution computed tomography (HRCT) of the chest indicated the presence of lymphadenopathy of the anterior and middle mediastinum. Therefore, a right-sided thoracoscopy was performed with excision of a 27-mm lymph node and a histological diagnosis of sarcoidosis was made. No medication for sarcoidosis was indicated. Complete normalization of mediastinal lymphadenopathy (verified on HRCT and chest X-ray) was confirmed 1 year following the thoracoscopy. To our knowledge, this is the first case wherein occurrence of sarcoidosis in a chronic hepatitis B patient treated with IFN-alpha is described. We suppose that IFN-alpha, as a potent stimulator of T-helper 1 (Th1) immune responses, may trigger the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis.