Jan Lata

The effect of probiotics on gut flora, level of endotoxin and Child–pugh score in cirrhotic patients: results of a double-blind randomized study

Objective To determine the effect of Escherichia coli Nissle (Mutaflor, Ardeypharm GmbH, Herdecke, Germany) on the intestinal colonization, level of endotoxin and liver functions in patients with liver cirrhosis. Methods Thirty-nine patients with liver cirrhosis diagnosed by means of biopsy and clinical examinations were randomly allocated to treatment with E. coli Nissle or placebo for 42 days. Standard clinical examination, biochemical and hematological examinations, level of endotoxin and microbiological examination of the stool were performed before and after the treatment. Results In comparing the treatment of E. coli Nissle and placebo, significant improvement of the intestinal colonization (P<0.001) in the E. coli Nissle group was described. We found a trend of significant lowering of the endotoxemia (P=0.07) and improvement of liver functions evaluated by Child–Pugh score (P=0.06). Conclusion E. coli Nissle seems to be effective in the restoration of normal colonic colonization and can probably lower endotoxemia in cirrhotic patients.

Incidence of chronic pancreatitis in the Czech Republic.

There have been only a few studies dealing with the incidence of chronic pancreatitis published. Over the last 80 years, original studies describing the incidence of chronic pancreatitis were undertaken, including studies in Scandinavia, Switzerland, Hungary and Poland. Incidence varied geographically, from 1.6 new cases per year among 100,000 inhabitants in Switzerland to 23 new cases among 100,000 inhabitants in Finland. The aetiology of 70% of all cases was alcoholic pancreatitis. The incidence of chronic pancreatitis in the Czech Republic is 7.9 per 100,000 inhabitants per year, similar to that of Denmark and Germany, but higher than that of Poland or Switzerland. In our study, the main aetiological factor was alcohol (65.4% of all cases, with consumption of alcohol of > 75.0 g/day).

Cytotoxicity of natural compounds in hepatocyte cell culture models: The case of quaternary benzo[c]phenanthridine alkaloids

The quaternary benzo[c]phenanthridine alkaloids (QBA) produce a plethora of species- and tissue-specific effects but the molecular basis of their biological activities remain mysterious. The objective of the present study was to investigate the cytotoxicity of QBA alkaloids, sanguinarine (SA), chelerythrine (CHE), fagaronine (FA), and the extract from Macleaya cordata in primary cultures of human and porcine hepatocytes. The cellular damage was assessed by the MTT assay, lactate dehydrogenase (LDH) leakage and the determination of intracellular glutathione (GSH) levels. The results are summarised as follows: (i) The alkaloids tested in doses 0.1 and 10 microM did not display statistically significant cytotoxicity for 0-3 h incubation; (ii) SA and CHE showed the dose- and time-dependent toxicity within the range 25-100 microM whereas FA was not toxic; (iii) the LDH leakage into the medium was higher for SA than for CHE, thus revealing a potent potential of SA to disturb cell-membrane integrity; (iv) after 3 h incubation with 100 microM SA/CHE, mitochondrial dehydrogenase activity (MTT assay) and the cellular GSH levels decreased to residual values of about 40% suggesting that mitochondria are unlikely to be a primary target for SA/CHE in the cell; (v) no differences were found in the response to QBA application in human vs porcine hepatocyte.

Probiotics in hepatology

The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established as well as potential pathogens. Furthermore, it influences the motility and perfusion of the intestinal wall, stimulates the intestinal immune system and therefore also the so-called common mucosal immune system, reducing bacterial translocation and producing vitamins. Immune homeostasis at mucosal level results from a controlled response to intestinal luminal antigens. In liver cirrhosis, there are many changes in its function, mostly an increase in bacterial overgrowth and translocation. In this review, probiotics and their indications in hepatology are generally discussed. According to recent knowledge, these preparations are indicated in clinical practice only for cases of hepatic encephalopathy. Probiotics are able to decrease the permeability of the intestinal wall, and decrease bacterial translocation and endotoxemia in animal models as well as in clinical studies, which is extremely important in the prevention of complications of liver cirrhosis and infection after liver transplantation. Probiotics could limit oxidative and inflammatory liver damage and, in some situations, improve the histological state, and thus non-alcoholic steatohepatitis could be considered as another possible indication.

Intestinal Obstruction and Perforation – The Role of the Gastroenterologist

Intestinal obstruction belongs to highly severe conditions in gastroenterology, namely from the viewpoint of quick and correct diagnosis as well as at determining rational and effective therapy. Etiological multifactorial characteristics leading to processes resulting in mechanical or dynamic obstruction of the intestine, often referred to as paralytic ileus, are undoubtedly serious factors influencing the accuracy of diagnosis and therapeutic approach. Digestive endoscopy is a mandatory method in the diagnosis of intestinal obstructions. Diagnostic endoscopy, colonoscopy in the involvement of the large intestine or enteroscopy in the case of incomplete obstruction of the small intestine are the methods indicated in the majority of obstructive intestinal lesions. Besides their diagnostic importance, they also enable an effective therapeutic approach which may immediately follow the diagnostic intervention. Besides endoscopy that – due to the nature of performance – belongs to invasive methods, the diagnosis of obstructive intestinal processes is unthinkable without the use of non-invasive imaging methods. Abdominal ultrasound examination, a widely applied method, provides – under optimal examination conditions – information, e.g., about the width of the intestinal lumen or about the intestinal wall thickness; however, the specificity of investigation is not always sufficient. Both specificity and sensitivity of exploration are increased by a plain X-ray of the abdomen supplementing the ultrasound examination. Better results are achieved when the abdominal cavity is inspected by means of spiral CT examination that is nowadays not fashionably but highly effectively applied in the modification of the so-called CT enteroclysis or CT colonography. The usage of magnetic resonance (e.g. virtual colonography) is similar, but its efficacy is lower than that of CT examination. From a gastroenterologist’s perspective, endoscopic examination is the fundamental diagnostic and therapeutic method. However, endoscopic examination is initially limited by the cardiopulmonary state of the patient – in a number of cases, first the cardiopulmonary condition must be stabilized, dysbalance of water and mineral state must be restored, and only then can endoscopic investigation be carried out. The application of enteroscopy in small intestine disorders is only suitable in cases where air must be aspirated from the region of the stomach and mainly small intestine as it happens, for example, in acute intestinal pseudo-obstruction. The success of complex conservative therapy in these states is reached in 80% of the cases. In acute and complete intestinal obstruction, a surgical treatment performed in time is the only method. In these cases, the importance of identification of obstruction and timing of the intervention performance from the viewpoint of the patient’s survival is explicitly the principal and life-saving concern. In acute intestinal obstructions developing in patients with malignant affection of the intestine, it is necessary to choose – according to the obstruction location and general state of the patient – either urgently performed surgery or palliative endoscopic intervention which is the reduction of the intestinal lumen of the growing tumor mass and following insertion of a drain. This method also concerns lesions localized in the left half of the abdominal cavity, i.e. in the region of the rectosigmoid and descending part of the colon. Most patients in whom acute intestinal obstruction developed on the basis of malignant disease are risk and polymorbid subjects, and acute surgical intervention may be either impracticable or highly stressing. In such cases it is therefore helpful to insert a drain and to bridge the obstructed area after restoring the cardiopulmonary state including adjustment of the aqueous and mineral environment. Later, the performance of an elective surgical intervention is safer. Another alternative before inserting a drain is the dilatation of the stenotic site by means of a balloon, followed by stenting. Up until today, various types of intestinal drains have been introduced – they have always been self-expanding metallic stents. Just the application of self-expanding stents in patients with malignant intestinal obstruction and the endoscopic possibility of dilatations of benign intestinal obstructions with dilatation balloons are the most significant therapeutic contributions of digestive endoscopy in these states.

Simultaneous Electrochemical Monitoring of Metabolites Related to the Xanthine Oxidase Pathway Using a Grinded Carbon Electrode

Using a mechanically grinded pyrolytic graphite electrode in edge orientation, a sensitive electrochemical method was developed for simultaneous determination of uric acid (UA), xanthine (XAN), hypoxanthine (HYP) (products of purine catabolism in human), allopurinol (ALO), and oxypurinol (OXY) (a drug used in treatment of purine catabolism disorders and its metabolite, respectively). It is demonstrated that differential pulse voltammetry in connection with this electrode can serve as a simple and efficient tool for monitoring transformation of purine catabolites (HYP --> XAN --> UA) catalyzed by xanthine oxidase (XO) as well as inhibition of this pathway by ALO being enzymatically converted to OXY. Our protocol is based on direct electrochemical measurement of oxidation peaks for each of the substances during in vitro reactions in a single detection step by the same electrode system. In addition, we show that the proposed electrochemical technique can be applied to parallel detection of metabolites involved in the XO pathway excreted in urine without any pretreatment of the clinical samples.

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.

Chronic Liver Diseases as Liver Tumor Precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.

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.

&NA; 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.