Impact of S3 training courses "Sedation and Emergency Management in Endoscopy for Endoscopy Nurses and Assisting Personnel" on the process and structure quality in gastroenterological endoscopy in practices and clinics - results of a nationwide survey.

INTRODUCTION: After the S3 Guideline Sedation in Gastrointestinal Endoscopy was published, a training curriculum for a three-day course for endoscopy nurses was developed. The aim of this study was to investigate what effect the course participation had on the daily routine process and structure quality by implementing a German-wide survey in gastroenterology practices and clinics. METHODS: A questionnaire with a total of 44 individual questions on personnel, space, and equipment structure, sedation, peri- and post-interventional monitoring, as well as discharge and complication management in endoscopy departments was sent to a total of 2113 course participants (1056 Institutions). They had completed the seminar between December 2008/January 2009 and June 2010. RESULTS: The response rate was 21.2 % (224 /1056). Fifty-four percent were from clinic endoscopy departments, 46 % from practices. Overall, some form of structural change occurred in 86.8 % of the clinics and in 84.5 % of the practices. New staff was hired in 28.1 % of the clinics and 12.6 % of the practices. Rosters were changed in 11.6 % of the clinics and 7.8 % of the practices. Almost all issues improved after course participation. However, they did not reach statistic significance with the exception of the availability of peri-interventional ECG-monitoring in practices. The "performance of sedation in threesomes" increased in clinics by more than 20 % and in practices by more than 15 %. The use of the ASA-classification to assess risk increased significantly in clinics (before 24 %, after 50 %) as well as practices (before 40 %, after 60 %) by more than 20 % (p = 0.0007 and p = 0.0385, respectively). The documentation of the discharge status (e. g. using checklists) more than doubled in clinics (before 19 %, after 41.3 %) and practices (before 17.5 %, after 38.8 %) after course completion. CONCLUSION: The only nationwide endoscopy nurses' survey on structure and process quality in endoscopy so far, shows that since the publication of the S3 guideline in 2008 numerous processes and structures have improved with respect to patient safety.

[Epidemiology of chronic hepatitis C in Germany--an analysis of 10,326 patients in hepatitis centres and outpatient units]. / Epidemiologie der chronischen Hepatitis C in Deutschland--Eine Analyse von 10,326 Hepatitis-C-Virus-Infizierten aus Schwerpunktpraxen und -ambulanzen.

Little is known about the epidemiology of chronic hepatitis C (CHC) in Germany and especially about the importance of transmission, duration of infection, genotypes, symptoms and quality of life of the patients. The current study prospectively evaluates epidemiological and clinical data of patients infected with the hepatitis C virus (HCV). Using online data entry, various characteristics of 10,326 untreated patients with CHC were documented from March 2003 until May 2006 in 352 centres all over Germany. Mean age of patients was 43.4 years. Patients infected by i.v. drug abuse were considerably younger (36.5 years) than the remaining patients (49.2 years). As indicated by their native language, 64.4% of the patients came from Germany and 19.2% from Russia. 61.7% were infected with genotype 1 and 34.9% with genotype 2 or 3. 45.5% of the patients had been infected by i.v. drug abuse. In at least 5.4% of the patients liver cirrhosis had been proved by biopsy. 63.5% of the patients felt an impairment of quality of life caused by CHC. In many patients infected with hepatitis C socio-economic issues are existent. This is reflected, i.e., in very high rates of unemployment in special subpopulations. Coinfections with hepatitis B and HIV occurred in 1.5% and 4.7%, respectively. Nearly 80% of patients were managed near their homes. The data of the 10 326 patients represent about 2% of all German patients with CHC. This database is up to now the largest of its kind and gives a representative insight into the epidemiological situation of CHC in Germany.

Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TGepsilon26 mice leading to the prevention of colitis.

BACKGROUND AND AIMS: Erroneous thymic selection of developing T lymphocytes may be responsible for the expansion of self reactive T cells or may contribute to the absence of regulatory T cells important in controlling peripheral inflammatory processes. Colitis in bone marrow (BM) transplanted Tgepsilon26 mice is induced by abnormally activated T cells developing in an aberrant thymic microenvironment. We investigated the protective role of regulatory CD4+CD25+ T cells in this model. METHODS: BM from (C57BL/6 x CBA/J) F1 mice was transplanted into specific pathogen free Tgepsilon26 mice (BM-->Tgepsilon26). Transplanted mice received no cells (control), sorted CD4+CD25+, or CD4+CD25- cells from mesenteric lymph nodes (MLN) of normal mice. MLN cell subsets were analysed using membrane markers. Cytokine secretion of MLN cells was measured using intracellular cytokine staining and cytokine secretion in anti-CD3 stimulated cell cultures. Colitis was measured by histological scores. RESULTS: CD4+CD25+ cells were reduced in the MLNs of BM-->Tgepsilon26 mice. Transfer of regulatory CD4CD4+CD25+ but not of CD4+CD25- cells reduced the number of MLN CD4+ T cells in BM-->Tgepsilon26 recipients and increased the number of MLN CD8+ cells, thereby normalising the CD4+/CD8+ ratio. CD4+CD25+ but not CD4+CD25- cell transfer into BM-->Tgepsilon26 mice reduced the number of tumour necrosis factor alpha+ CD4+ cells and increased the secretion of transforming growth factor beta by MLN cells. Transfer of 3 x 10(5) CD4+CD25+ cells after BM transplantation into Tgepsilon26 mice prevented colitis whereas CD4+CD25- cells had no protective effect. CONCLUSIONS: These results suggest that defective selection or induction of regulatory T cells in the abnormal thymus is responsible for the development of colitis in BM-->Tgepsilon26 mice. Transfer of CD4+CD25+ cells can control intestinal inflammation in BM-->Tgepsilon26 mice by normalising the number and function of the MLN T cell pool.

Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia.

BACKGROUND AND AIMS: The hepatic peptide hormone hepcidin, which has recently been isolated from human plasma and urine, is thought to be a central regulator of iron homeostasis. We investigated the presence and cellular localisation of hepcidin in the liver and developed a non-invasive assay to analyse its regulation in patients with hereditary haemochromatosis (HH), chronic renal insufficiency (CRI), and renal anaemia (RA). METHODS: Expression and localisation of hepcidin was shown by reverse transcription-polymerase chain reaction, western blot, immunocytochemistry, and immunofluorescence in human and guinea pig liver. Serum concentrations were determined in various groups of patients using a sensitive enzyme linked immunosorbent assay (ELISA). RESULTS: Western blot analysis with region specific antibodies identified a approximately 10 kDa peptide corresponding to the apparent molecular mass of pro-hepcidin. Localisation studies revealed that pro-hepcidin is expressed at the basolateral membrane domain of hepatocytes and is also present in blood. We developed a stable sensitive ELISA for detection and determination of pro-hepcidin in human serum. Mean pro-hepcidin level in human serum of healthy volunteers was 106.2 ng/ml. Enhanced levels of pro-hepcidin (148.1 ng/ml) were found in patients with CRI but normal haemoglobin values, indicating that the kidneys may metabolise and/or eliminate the circulating hormone. In contrast, concentrations of pro-hepcidin were significantly decreased in patients with HH (70.2 ng/ml) and also in patients with RA (115.0 ng/ml) compared with the CRI group. CONCLUSIONS: From the detection of pro-hepcidin in human serum, we conclude that the prohormone may be involved in the regulation of iron metabolism in HH. Decreased pro-hepcidin levels could play an important role in the pathogenesis of HH.

Interferon alfa2a induction therapy in combination with ribavirin and amantadine for the treatment of naive patients with chronic HCV infection.

Pilot studies have suggested that the addition of amantadine to interferon (IFN) is effective against hepatitis C virus (HCV). Furthermore, IFN induction therapy seems to improve virological response rates. In this open, randomized, multicentre trial we compared safety and efficacy of a triple therapy comprising IFN alpha 2a, ribavirin and amantadine using high induction doses (6 MU IFN alpha daily for the first 6 weeks) against a therapy with standard IFN alpha dosages over the entire treatment period plus amantadine and ribavirin. A total of 158 naive patients with chronic HCV infection were randomized 1:1. Group A (n = 81): induction therapy with 6 MU IFN alpha daily for 6 weeks, followed by 6 MU three times a week (tiw) for 18 weeks and then 3 MU tiw until week 48. Group B (n = 77): standard therapy with 6 MU IFN alpha tiw for 24 weeks, followed by 3 MU until week 48. All patients received oral ribavirin (10 mg/kg/day) and amantadine (200 mg/day). The triple therapy was safe and well tolerated. There were no significant differences between the groups with respect to biochemical response rates. Groups A and B did not differ in virological response rates at the end of treatment (33%vs 35%) or at the end of the 6 month follow up period (37%vs 39%). We could not detect favourable effects on sustained virological response rates using induction therapy, in either genotype 1 or non-1 infected patients. In summary, induction therapy with 6 MU IFN alpha daily did not result in increased overall response rates compared with standard IFN alpha dosages of 6 MU tiw.

Immunogenicity of an accelerated vaccination regime with a combined hepatitis a/b vaccine in patients with chronic hepatitis C.

OBJECTIVES: Hepatitis A (HAV) and B (HBV) vaccinations are recommended in patients with chronic liver diseases. METHODS: We prospectively investigated immunogenicity and safety of an accelerated vaccination protocol (0-7-21 days) with the combined hepatitis A/B vaccine (Twinrix(R)) versus the standard vaccination scheme (0-1-6 months) in hepatitis C virus-infected patients versus healthy volunteers. RESULTS: Local and general symptoms were mostly mild in all groups. One month after completion of the accelerated vaccination or standard vaccination, with the combined hepatitis A/B vaccine anti-HAV seroconversion rates (>33 IU/l) were 89 % and 88 % in HCV-infected patients. Initial HCV-nonresponders developed protective anti-HAV antibodies in 94 % and 96 % after a booster dose. According to the anti-HBs seroprotection rate, HCV-infected patients developed protective anti-HBs titres (>10 IU/l) in 77 % and 82 % of cases one month after the accelerated and the standard vaccination scheme-at month 2 and 7, respectively. This anti-HBs seroprotection rate could even be increased to 84 % and 85 % when initial HCV-infected nonresponders where given a booster dose with the combined hepatitis A/B vaccine. Protective anti-HAV and anti-HBs titers were achieved as early as month 2 after the accelerated vaccination schedule in the majority of HCV-infected patients. Healthy subjects developed protective anti-HAV titers and anti-HBs titers in 100 % and 98 % after the accelerated and standard vaccination protocol. CONCLUSIONS: This study is the first to have demonstrated that the accelerated combined hepatitis A/B vaccination is both safe and highly immunogenic against HAV and HBV in HCV-infected patients with well compensated liver disease.

[Clinical usefulness and diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin]. / Klinischer Nutzen und diagnostische Bedeutung der Leberbiopsie bei chronisch erhöhten Leberwerten nicht viraler Genese.

BACKGROUND: In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. PATIENTS AND METHODS: 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. RESULTS: Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. CONCLUSION: Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.

Immunogenicity of two accelerated hepatitis B vaccination protocols in liver transplant candidates.

OBJECTIVE: It is common practice to immunize patients against hepatitis B virus infection prior to orthotopic liver transplantation (OLT). We compared the seroprotection rates of two accelerated schedules with a recombinant hepatitis B vaccine in patients awaiting OLT. DESIGN AND METHODS: Patients were prospectively recruited and vaccinated with either 20 micrograms (group 1, n = 14) or 40 micrograms (group 2, n = 20) hepatitis B surface antigen per dosage. Thirty-nine healthy volunteers served as a historical control group. Patients in all groups were vaccinated with an accelerated schedule (0, 7 and 21 days). All patients underwent clinical and laboratory examinations (HBs antibodies, CD4/CD8 ratio, transaminases). RESULTS: The accelerated hepatitis B vaccination schedules were well tolerated. Eight weeks after the third injection, no significant differences in seroprotection rates were observed between group 1 (31%) and group 2 (26%). There was no correlation with respect to seroconversion rates and gender, smoking habits or CD4/CD8 ratio. CONCLUSION: These data suggest that accelerated vaccination schedules with a recombinant hepatitis B vaccine are safe and well-tolerated, but only achieve poor seroconversion rates in OLT candidates. Increasing the vaccine dose to 40 micrograms hepatitis B surface antigen per injection did not result in a higher response rate. Because of the low risk of acquiring de novo hepatitis B infection after transplantation, it should be questioned whether routine hepatitis B vaccination with standard recombinant vaccines prior to liver transplantation should be recommended any longer.

Combination therapy with interferon-alpha 2b and ribavirin for the treatment of relapse patients and non-responders with chronic HCV infection.

BACKGROUND: Treatment of patients with chronic hepatitis C after failure of an interferon monotherapy remains controversial. While relapse patients have a sustained response after a combination therapy with interferon-alpha 2b 3 x 3 MU/week plus ribavirin 1,000/1,200 mg daily for 24 weeks in up to 49%, the standard therapy for initial non-responders remains to be determined. METHODS: We therefore conducted a large multicenter trial to compare efficacy and safety of a combined interferon/ribavirin therapy in 327 non-responders and 181 relapse patients with chronic HCV infection outside of highly specialized institutions. RESULTS: After 6 months therapy with interferon-alpha-2b 3 MU thrice a week plus ribavirin 1,000/1,200 mg daily for 24 weeks 31% of relapse patients and 11% of initial non-responders achieved a sustained response according to an intent to treat analysis. CONCLUSIONS: These data could not confirm the high rate of sustained responders in relapse patients. In addition we were only able to induce a sustained response in every tenth non-responder. These results might reflect the realistic sustained response rates in a non-biased European population of HCV-infected patients.

[Retrospective cohort study of lamivudine therapy in patients with chronic hepatitis B]. / Retrospektive Kohortenstudie zur Lamivudintherapie bei Patienten mit chronischer Hepatitis B.

BACKGROUND AND AIMS: Lamivudine, a nucleoside analogue with specific antiviral activity against the hepatitis B virus, is now available as an alternative therapeutic option to standard interferon-alpha treatment in chronic hepatitis B. Larger studies with lamivudine treatment in chronic hepatitis B were mainly performed in North America and Asia. Data on treatment responses in European patients are sparse. Therefore, we evaluated the efficacy and safety of lamivudine therapy in Central European patients and compared the data with the results from international trials. PATIENTS AND METHODS: In this retrospective, multicenter, cohort study, 95 patients with chronic hepatitis B (median age: 40.4 years, male: 87 patients, female: 8 patients, HBeAg positive: 47 patients, anti-HBe positive: 48 patients), who were treated with lamivudine (100-300 mg/d per os) between 1997 to 1999, were enrolled. RESULTS: During lamivudine treatment a virologic response with HBeAg to anti-HBe seroconversion was achieved in 22/47 (47%) of the HBeAg positive patients. Pretreatment ALT levels (> threefold the upper limit of normal; p = 0.03) and HBV-DNA serum concentration (< or = 100 pg/ml; p = 0.08) were identified as positive predictors for virologic responses. The virologic response was sustained in six of nine patients who had a follow-up period (median 26 weeks). In anti-HBe positive patients a virologic response with undectable HBV-DNA levels was achieved in 35/48 (73%) patients during lamivudine treatment. Side effects during lamivudine therapy were generally mild and reversible. CONCLUSIONS: In this retrospective cohort study virologic end-of-treatment responses to lamivudine monotherapy in patients with chronic hepatitis B were comparable with yet reported international trials. Thus, lamivudine represents a cost-effective and well tolerable option in addition to IFN-alpha in the treatment of chronic hepatitis B.

Spontaneous regression of intrahepatic lesions mimicking metastatic disease.

This is a case report of a 53-year-old male with chronic hepatitic C infection presenting with weight loss and elevated liver function tests. Repeated ultrasonography, computed tomography and magnet resonance imaging showed multiple intrahepatic lesions suggestive of metastatic disease. Repeated ultrasound-guided biopsies from the lesions as well as from the adjacent normal appearing liver tissue revealed no malignancy but showed inflammation and significant fibrotic tissue, consistent with chronic hepatitis C. 2 years after the first admission liver function tests were all within the normal range and remained so until today. Computed tomography at that time showed complete remission of all intrahepatic lesions. The exact diagnosis remained elusive but the rare case of reversible focal fibrosis is the most likely cause of these spontaneously regressive lesions.

Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?

A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany since 1997. We investigated possible differences in immunogenicity and safety when changing over from vaccinations with monovalent vaccines made by different manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open, randomized, multicenter trial. We therefore compared four different schemes changing over from concomitant vaccinations with monovalent vaccines against hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against hepatitis A+B with three injections of the combined hepatitis A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly mild in all five groups. With complete three-dose course using the combined vaccine or an early changeover from monovalent vaccines to the combined vaccine, higher overall anti-HBs seroprotection rates and geometric mean concentrations (GMCs) against hepatitis B could be achieved as early as after 2 months as compared to those groups switching later to the combined vaccine. This study demonstrated for the first time that switching from monovalent hepatitis A and B vaccinations to the combined hepatitis A and B vaccination has no negative influence on the tolerability and improves the immunogenicity.

[Pulmonal sarcoidosis: A rare side effect of interferon-alpha treatment for chronic hepatitis C infection]. / Pulmonale Sarkoidose: eine seltene Nebenwirkung einer Interferon-alpha-Therapie bei chronischer Hepatitis-C-Infektion.

This is a case report of a 44-year-old woman who received a 1-year-treatment with interferon-alpha for chronic hepatitis C virus infection. 3 months after cessation of the therapy she relapsed and was successfully retreated 12 months with a combination of interferon-alpha and ribavirin thereafter. During the treatment the patient developed a typical flue-like syndrome, dry cough with exertional dyspnea that was initially interpreted as a typical side effect of interferon-alpha treatment. Due to the persisting cough, further radiologic and histologic work up was done and results were significant for interstitial sarcoidosis. After interferon-treatment was stopped the pulmonary symptoms resolved completely while pathologic changes in radiographic imaging persisted. Interferon-alpha may have contributed to the development and progression of sarcoidosis by activation of cellular immunity. Although there are only few reports about pulmonary sarcoidosis associated with interferon-alpha treatment, this entity should be included in the differential diagnosis of putative side effects of interferon-alpha therapy.

Clinical relevance of hepatitis G virus (HGV) infection in heart transplant patients.

To investigate whether the recently discovered hepatitis G virus (HGV) influences the clinical outcome of heart transplant recipients under immunosuppression, we determined the prevalence of HGV infections correlated with liver function and survival in 51 patients. Presence of HGV RNA and anti-E2, a marker for resolved HGV infection, were serially tested in sera from patients before and after heart transplantation (HTX) by nested RT-PCR and ELISA. Four of 51 (7.8%) patients before transplantation, and 22 of 50 patients (44%) after transplantation showed signs of persistent or resolved HGV infection. HGV infection was not associated with impairment of liver function or with patient survival. In summary, presence of HGV infection does not influence the clinical outcome in heart transplant patients.