Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population.

Colonisation of the hepatobiliary system with bile-resistant Helicobacter spp. has been proposed as a novel risk-factor in the pathogenesis of gall-bladder carcinoma (GBC). There are reports that biliary Helicobacter colonisation is frequent in countries with a high incidence of gall-bladder carcinoma. However, the prevalence of Helicobacteraceae in the gall-bladders of patients with GBC in Germany, a region with a low incidence of GBC, is unknown. Therefore, gall-bladder tissue from 99 patients who had undergone cholecystectomy was tested, including 57 cases of gall-stone disease (GSD), 20 cases of GBC, and 22 control patients. The presence of Helicobacter spp. was investigated by culture, immunohistochemistry and a group-specific PCR targeting the 16S rRNA gene of all currently known Helicobacteraceae. Of the 99 cases investigated, only one patient with GSD was PCR-positive for Helicobacteraceae. For this individual, sequence analysis of the 16S rRNA gene showed that it had homology closest to the 16S rRNA sequence of Helicobacter ganmani. Helicobacteraceae were not detected by culture or immunohistochemistry. The low prevalence of Helicobacteraceae in the gall-bladders investigated suggests that Helicobacteraceae do not play a predominant role in the pathogenesis of GSD and GBC in the German population. The low prevalence could be a possible explanation for a relatively low incidence of GBC in the German population, despite the fact that GSD, the major risk-factor for GBC, is highly prevalent.

Changes in the acute phase complement component and IL-6 levels in patients with chronic hepatitis C receiving interferon alpha-2b.

In order to study the effect of interferon alpha on the levels of acute phase complement proteins in vivo, serum concentrations of C9 and C1-inhibitor (C1-INH) were measured in patients with chronic hepatitis C before and 3 months after the beginning of interferon alpha2b therapy. Serum levels of the activation product of terminal complement pathway, C5b-9, HCV RNA and IL-6 were also determined. IFN alpha treatment significantly (P<0.0001) increased the serum concentrations of both complement proteins. C5b-9 levels were found to significantly decrease during the same period of time. When the patients were divided into responders or non-responders (more or less than 50% decrease in plasma HCV RNA concentrations) C9 and C1-INH levels were elevated only in the responder patients. There was no correlation between the changes of IL-6 levels or the amounts of IFN alpha administrated on one hand, and the changes in the complement protein levels on the other. These findings suggest that the marked increase in the serum concentrations of the acute phase complement proteins is a secondary phenomenon due to the IFN alpha-caused diminution of the viral load and the resulting immune complex-induced complement activation.

[Cryoglobulinemia in chronic liver diseases: cause or consequence?]. / Cryoglobulinaemia krónikus májbetegségekben: ok, vagy következmény?

Cryoglobulinemia occurs in a wide spectrum of infectious, autoimmune, neoplastic, renal and liver diseases. In the first part of the publication the authors give a review about laboratory and clinical features of cryoglobulinemia and its associated syndromes. In essential mixed cryoglobulinemia (arthralgia-purpura-weakness) clinical and laboratory evidence of liver involvement are frequently found. In chronic liver diseases of different etiologies mixed cryoglobulins can be detected. In 30-94% of cases of chronic hepatitis C virus infection and chronic liver diseases related to hepatitis C virus laboratory signs (and occasionally clinical symptoms as well) of mixed cryoglobulins have recently been reported. In the cryoprecipitates of these cryoglobulins positive patients markers of hepatitis C virus have been detected. The presence of high prevalence of cryoglobulins in chronic hepatitis C virus infection and chronic liver diseases related to hepatitis C virus suggests a significant role for this hepatotropic virus in the pathogenesis of mixed cryoglobulins. On the other side, the impact of impaired liver function in the clearance of (cryo)immunocomplexes from the serum can be a causative factor in the production of cryoproteins in chronic liver disease of different etiologies.

[H2-receptor antagonists and alcohol: clinical significance]. / A H2-receptor blokkolók és az alkohol: klinikai következtetések.

The aim of the review is to evaluate the putative clinical interactions between alcohol metabolism and the administration of H2-receptor antagonists. Places of the first-pass metabolism of ethanol in the body have been investigated as well. According to the in vitro experimental results the H2-receptor antagonists can inhibit the ethanol metabolism which may have clinical relevance. When low doses of alcohol (below 0.3 g/kg) are given per os, the administration of H2-receptor antagonists results in an increase in the blood ethanol concentrations. Since that challenged increase never exceeds the level of 0.3/1000 blood alcohol concentration, it has hardly any clinical or medico-legal significance.

[Practical considerations of immunoprophylaxis in viral hepatitis]. / Hepatitis vírusfertözések immunprofilaxisának gyakorlati vonatkozásai.

Hepatitis virus infections belong to the major etiological factors of both acute and chronic liver diseases. During the last years--apart from the passive immunoprophylaxis through the administration of immunoglobulin--safe and efficacious hepatitis vaccines (against hepatitis A and B viruses) has also became available in Hungary. In this review the authors focus on the practical considerations of the immunoprophylaxis of hepatitis viruses. General consensus concerning the clinical use of hepatitis A vaccine has not been accepted, and human immunoglobulin is the only acceptable measure to prevent postexposure hepatitis A virus infection. Hepatitis B immunoglobulin (HBIG) is administered to prevent hepatitis B infection after exposure of HBV-contaminated body fluids and in infants born to HbsAg-positive mothers. Recombinant hepatitis B vaccine has the crucial note in the WHO's program for eradication of hepatitis B. While in the areas of high endemicity the implementation of universal hepatitis B vaccination is recommended, in the countries with low HbsAg-carrier prevalence infants' and/or adolescents' vaccination can offer alternative choices. Prevention of health-care workers against hepatitis virus infection and the vaccination of patients with chronic liver disease are also of great importance. There is also an urgent need to establish multidisciplinary professional cooperation to be able to carry out effectively the WHO's recommendations for prevention of hepatitis B infection.

[Activity of neutral endopeptidase in serum of patients with primary biliary cirrhosis]. / Neutrális endopeptidáz-aktivitás primer biliaris cirrhosisos betegek szérumában.

Neutral endopeptidase (neprilysin; EC 3.4.24.11) is present in the brush border membrane, for example in the bile ducts. We investigated serum neprilysin activity and its correlation with cholestatic markers in patients with primary biliary cirrhosis. Sera of 39 patients with primary biliary cirrhosis (37 females, 2 males, mean age 45 years, range 24-71 years) were investigated. Twenty-seven healthy volunteer subjects served as control. Serum neprilysin activity was measured by a sensitive microplate-based continuous monitoring kinetic assay. Succinyl-alanyl-alanyl-phenyl-alanyl-4- nitroanilide was used as substrate. For statistical analysis Kruskal-Wallis ANOVA by ranks and Mann-Whitney U test were used. The neprilysin activities were significantly higher in stages III (mean 13.2 +/- SD 10.8 U/l) and IV (21.8 +/- 17.5) than in the control subjects (2.4 +/- 2.9, p < 0.01). There was no significant difference in neprilysin activity between the patients with stages I and II, or between stage I + II (2.88 +/- 3.0) and the control. Positive correlation was found between the activity of neprilysin and serum bilirubin, alkaline-phosphatase and gamma-glutamyl-transferase (p < 0.005 for each). In this study we confirmed that serum neprilysin activity is elevated in patients with primary biliary cirrhosis at advanced stages and the elevation correlated with the cholestatic markers. The increased neprilysin activity seems to be an indicator for the severity and progression of the disease.

[Cryoglobulinemia and chronic liver diseases]. / Kryoglobulinämie und chronische Lebererkrankungen.

Cryoglobulinemia can be associated with several infections, immunoproliferative tumors, chronic liver, renal and systemic autoimmune diseases. In the first part of the publication the authors give a review of the main clinical and laboratory properties of cryoglobulins. In essential mixed cryoglobulinemia syndrome (purpura, arthralgia, weakness) clinical and laboratory signs of damaged liver function can often be seen. However, there are mixed cryoglobulins in chronic liver disease of different etiologies as well. In 30-94% of patients with hepatitis C virus infection and hepatitis C virus-induced chronic liver diseases laboratory signs (occasionally clinical symptoms as well) or mixed cryoglobulinemia can be diagnosed. Serological markers of hepatitis C virus infection have been found in the cryoprecipitates of patients with mixed cryoglobulinemia. A high prevalence of mixed cryoglobulins in serum of patients with chronic hepatitis C virus infection and hepatitis C virus-induced chronic liver disease suggests that this virus has a significant role in the pathogenesis of mixed cryoglobulins. Also, an impaired clearance function of the liver in the uptake of cryo(immuno)complexes may be an important causative factor in the production of cryoglobulins in chronic liver diseases of different etiologies.

Do autoantibodies predict autoimmune liver disease in primary Sjögren's syndrome? Data of 180 patients upon a 5 year follow-up.

OBJECTIVE: To evaluate the clinical value of autoantibodies as serological markers to predict autoimmune liver diseases in primary Sjögren's syndrome (SS). MATERIALS AND METHODS: 180 patients who met the European diagnostic criteria for SS but without a history of liver disease were studied upon a 5 year follow-up. Sera taken at enrolment were evaluated by immunofluorescence analysis (IF-AMA) on rat liver, stomach and kidney sections, enzyme-linked immunosorbent assay using rat mitochondrial, microsomal and soluble liver antigens and Western blot (WB) analysis using rat mitochondrial antigens. RESULTS: At presentation, 152 (84%) sera had autoantibodies. Antinuclear antibodies (ANA) were expressed in 58% of patients and displayed three distinct patterns (speckled, homogenous and anticentromere). Smooth muscle autoantibodies (SMAs) and parietal cell autoantibodies were found in 39 and 4.5% of patients, respectively. Three patients presented antimitochondrial antibodies by IF-AMA, and two of them developed symptomatic primary biliary cirrhosis (PBC). Two patients without IF-AMA and without evidence of cholestasis had PBC-specific AMA (anti-PDC-E2 and anti-BCKADC-E2). However, these two patients and the third IF-AMA-positive woman remained free from symptoms and biochemical signs of PBC. Autoimmune hepatitis (AIH) (n = 2), 'overlap syndrome' of AIH and chronic hepatitis C (n = 1) and autoimmune cholangiopathy (AIC) (n = 1) were diagnosed in four patients. CONCLUSIONS: Patients with IF-AMA usually develop symptomatic PBC upon a 5 year follow-up. Our findings support the idea that patients without IF-AMA, who express PBC-specific AMA, are in early, asymptomatic stage of the disease. High-titre SMA and IF-AMA are the most specific indicators for AIH and PBC.

Effects of interferon treatment on the glucose metabolism of patients with chronic hepatitis C.

Background: The authors report on changes in carbohydrate metabolism observed in 32 patients undergoing therapy with interferon-alpha for chronic hepatitis C. Methods: Diabetes had been diagnosed in three patients and impaired glucose tolerance ascertained in one patient before interferon therapy was started. The remaining 28 patients were non-diabetic. Interferon-alpha was administered in 3-MU doses three times per week. Results: Glucose tolerance deteriorated in two of the three diabetics, and eventually these patients had to be switched from oral hypoglycemic agents to insulin. The patient with impaired glucose tolerance at baseline progressed gradually to overt diabetes. Nine of the 28 previously non-diabetic patients developed impaired glucose tolerance during interferon therapy. Conclusion: The deleterious effects of interferon-alpha on carbohydrate metabolism proved to be reversible. Regular monitoring of the glucose level of patients during and after interferon therapy is mandatory.

LKM3 autoantibodies in hepatitis C cirrhosis: a further phenomenon of the HCV-induced autoimmunity.

Chronic hepatitis C is frequently associated with laboratory markers-including LKM1 autoantibodies--of autoimmunity. A 62-yr-old woman with hepatitis C cirrhosis presented autoantibodies against liver and kidney microsomal proteins. By further evaluation of autoantibodies using ELISA and immunoblotting LKM1 and LKM3 autoantibodies could be revealed. The target antigen of LKM3 autoantibodies proved to be UGT-1.1 isoenzyme. In the absence of chronic hepatitis D infection or autoimmune hepatitis type 2, this is the first case that reports the occurrence of LKM3 autoantibodies in HCV-induced chronic liver disease.

Study of hepatitis C virus infection in 213 Hungarian patients with Sjögren's syndrome.

In the current study we investigated 213 randomly selected Hungarian patients diagnosed with primary Sjögren's syndrome (SS). All patients were monitored for hepatitis C virus (HCV) infection and 13 were positive. We compared HCV-negative and -positive patients and made observations on how HCV infection alters the clinical and laboratory features of Sjögren's syndrome. On the basis of these findings, we conclude that HCV infection is more frequent in Hungarian SS patients than in the normal population and that the presence of this virus has a disease-modifying effect on SS.

C5b-9 and interleukin-6 in chronic hepatitis C. Surrogate markers predicting short-term response to interferon alpha-2b.

BACKGROUND: Available data and our observations suggest that elevated levels of interleukin (IL)-6 and -10 and some complement parameters may be associated with a poor response to IFN alpha. We evaluated how baseline levels of C5b-9, IL-6, and IL-10 influence the outcome of IFN alpha treatment. METHODS: Fifty-one patients with established chronic hepatitis C were enrolled and treated with IFN alpha-2b. Before and after a 12-week-IFN-treatment (3 MU or 5 MU tiw) serum levels of IL-6, IL-10, C5b-9 and RNA of hepatitis C virus (HCV) were assessed. Sera of 46 sex- and age-matched, healthy blood donors served as control. RESULTS: While two-thirds of patients was considered 'responder', 14 patients had no significant decrease either in HCV RNA or in ALT levels. In the responder's group lower baseline levels of IL-6 and C5b-9 were found than those in the 'non-responder' group. As a result of IFN therapy HCV RNA and C5b-9 levels significantly decreased. While the serum concentration of IL-6 increased during the follow-up period, regarding IL-10, no change was observed. In patients with 'low' baseline levels of C5b-9 (<2053 ng/ml) IFN alpha resulted in a significantly (P = 0.0005) higher decrease in HCV RNA level. Regarding 'low' IL-6 values (< 1.47 pg/ml) similar but somewhat less significant (P = 0.0039) difference was found if the change of HCV RNA was investigated. The odds ratio of patients with low IL-6 and/or C5b-9 to responding to IFN alpha treatment was almost 10 times (CI: 9.1 (1.8-50.9)) higher as compared with patients without 'low' levels of these parameters. CONCLUSION: Our data suggest that serum level(s) of IL-6 and/or C5b-9 taken prior to the initiation of IFN treatment may serve as surrogate marker(s) in evaluating patients with chronic hepatitis C whether to get IFN alpha in monotherapy or to consider having combination therapy in the form of IFN alpha-ribavirin.