PubMed Health⌕ Search

Biomedical subjects

H Wedemeyer

Publications and source records attributed to H Wedemeyer.

At least 19 recordsLinked to original sources
PubMed2007

Induction of hepatitis C virus (HCV)-specific T cells by needle stick injury in the absence of HCV-viraemia.

BACKGROUND: The risk of hepatitis C virus (HCV) infection after occupational exposure is low with seroconversion rates between 0 and 5%. However, factors associated with natural resistance against HCV after needle stick injury are poorly defined. HCV-specific T-cell responses have been described in cross-sectional studies of exposed HCV-seronegative individuals. MATERIALS AND METHODS: In this study, we prospectively followed 10 healthcare professionals who experienced an injury with an HCV-contaminated needle. Blood samples were taken on the day or the day after the event and at different time points during follow-up for up to 32 months. HCV-specific T-cell responses were investigated directly ex vivo and in T-cell lines. RESULTS: None of the individuals became positive for HCV-RNA in serum tested with the highly sensitive transcription-mediated amplification (TMA)-assay or in peripheral blood mononuclear cells (PBMC). All of them remained anti-HCV negative throughout follow-up. At the time of injury, HCV-specific CD4+ T-cell responses were already detectable in two individuals and became detectable thereafter in three additional persons. Transient HCV-specific CD8+ T-cell responses developed in two HLA-A2 positive patients, which became negative until the most recent follow-up after 5 and 17 months, respectively. CONCLUSION: We demonstrate the development of HCV-specific T cells in HCV-exposed individuals after needle stick injury indicating subinfectious exposure to HCV. T-cell immunity against HCV may contribute to the low prevalence of HCV in medical healthcare professionals in Western countries.

Adult↗
PubMed2006

Prevalence of hepatitis C in a German prison for young men in relation to country of birth.

A high prevalence of hepatitis C (HCV) virus infection of up to 80% has been reported for injecting drug users (IDUs) in prison communities. However, there are only very limited data available on the prevalence and course of HCV in young offenders. We performed a study on hepatitis C markers in the largest German Young Offenders' Institution (YOI), a prison for men (aged 16-24 years). In 2002, all 1176 incoming offenders were asked to participate in the study of whom >95% agreed. Ninety-seven inmates (8.6%) tested positive for anti-HCV or HCV RNA, 79% of whom were viraemic. None of the patients had evidence of cirrhosis at presentation. Interestingly, six individuals (6%) tested positive for HCV RNA in the absence of anti-HCV antibodies, four of whom cleared HCV spontaneously during follow-up without either clinical signs of acute hepatitis or developing HCV antibodies. Hepatitis C markers were significantly more prevalent among immigrants from the former Soviet Union (NIS) than among German inmates (31% vs. 6% respectively, P<0.0001). HIV co-infection was found in five individuals, all of whom were German. In contrast, hepatitis B surface antigen (HBsAg) was detected in five NIS immigrants, one Lebanese and one German inmate. HCV genotypes 2 and 3 were more prevalent in immigrants than in German inmates, while biochemical parameters did not differ significantly between the two groups. In conclusion, the prevalence of hepatitis C was relatively low among inmates of German YOIs although there were significant differences in relation to the country of birth. Our data highlight the need for educational programmes for young offenders in order to prevent the further spread of HCV.

Adolescent↗
PubMed2006

[Three years of vertical networking in the German Network of Competence on Viral Hepatitis: what can we learn from the usage of different information tools?].

Treatment of patients with viral hepatitis is time-consuming and sometimes complicated. Several sources of information have been established as internet sites, however systematic analyses of the need and use of these information platforms are lacking. The Competence Network on Viral Hepatitis (Hep-Net) was established in 2002 and offers a telephone hotline, an e-mail service and a home page with frequently asked questions (FAQs). On the internet pages "FAQs" 38 125 hits have been registered on single "question-answer-units" within three years. In a half of the cases the question are associated with modes of transmission. In contrast, patient's questions in e-mail and the telephone hotline are mainly dealing with the treatment of hepatitis C. More than 46 % of the physician's questions referred to unclearness in indications for treatment. Questions on specific medical problems of individual patients and, in e-mail, also on legal issues played a major part. Many of these questions have not been addressed in the actual guidelines in Germany. In summary, the Hep-Net vertical networking tools represent a fast, quality-assured endorsement to the daily management of patients with viral hepatitis. The combination of internet, e-mail service and telephone hotline gives consideration to individual necessities of patients and physicians. However, the detailed analysis of usage also shows limitations of current guidelines which should be considered during updating.

Community Networks↗
PubMed2006

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Adult↗
PubMed2006

Cytotoxic CD4 T cells in viral hepatitis.

CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus-infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive CD4+ T cells in viral hepatitis was highly variable ranging from < 1% to more than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28-, CD27-). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04), perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4-/CD8- lymphoid cells (P = 0.002). Differentiated CD27- effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin-positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.

Adult↗
PubMed2006

Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy.

Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.

2-Aminopurine↗
PubMed2006

Treating viral hepatitis C: efficacy, side effects, and complications.

The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy--pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.

Amantadine↗
PubMed2005

Diagnostic algorithm for chronic hepatitis C virus infection: role of the new HCV-core antigen assay.

BACKGROUND: The diagnosis of chronic hepatitis C virus infection is based on nucleic acid testing (NAT) for HCV-RNA. We evaluated whether total HCV core antigen testing could be a substitute for NAT testing. PATIENTS AND METHODS: Samples from 192 untreated chronic HCV positive patients previously tested for HCV-RNA by four different commercially available assays (SuperQuant, Amplicor HCV Monitor v 1.0 and v 2.0, Quantiplex) were tested for total HCV core antigen using the Ortho trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ, USA). Furthermore, 52 HCV-RNA positive paired serum and plasma samples were analysed. Finally, inter-assay coefficients of variation for core antigen were determined by repeated testing of 59 samples. RESULTS: 172/192 (89.6 %) samples from untreated HCV patients showed positive results with the trak-C assay. Importantly, all but two trak-C positive samples were NAT positive. Only four of the twenty trak-C negative samples tested positive by two NAT assays with viral loads below 30,000 copies/mL. Moreover, HCV core antigen levels correlated significantly with HCV-RNA levels (r > 0.72; p > 0.001), gave consistent results in paired serum and plasma samples (r = 0.991), and showed a very low inter-assay variability (r = 0.943) independent of genotype. CONCLUSION: Based on the performance characteristics, easiness of use, and potential lower cost of the core Ag assay, we propose an alternative testing algorithm for establishing the diagnosis of chronic HCV infection in which the trak-C assay could substitute for NAT as the first choice for detection of HCV viraemia in anti-HCV positive individuals. NAT would only be necessary in rare cases with low viral load.

Algorithms↗
PubMed2005

Superiority of standard interferon-alpha2b compared to pegylated interferon-alpha2b (12 kDa) in a hemodialysis patient with chronic hepatitis C?

INTRODUCTION: Hepatitis C virus (HCV) infection represents an important problem for hemodialysis patients. Interferon-alpha (IFN-alpha) three times per week has been shown to clear HCV RNA in a substantial proportion of renal transplant candidates, and may thereby prevent the deleterious effect of immunosuppressive treatment on progression of liver disease in HCV-positive patients after renal transplantation. Data on the efficacy of the new pegylated interferons in hemodialysis patients are limited and general recommendations are absent. CASE: A 41-year-old Caucasian man infected with hepatitis C genotype 1b was admitted with a history of renal transplantation in 1990, and reintroduced hemodialysis in 1997 because of chronic rejection. Antiviral therapy with pegylated interferon-alpha2b (120 microg/oiw) and ribavirin (400 mg/tiw) was initiated. A virological and biochemical response with undetectable HCV-RNA was evident already after six weeks. Two weeks later, however, HCV-RNA became detectable again with 18.000 IU/ml. The treatment regimen was changed to standard-IFN-alpha2b (3 MU/tiw). Shortly thereafter, ribavirin had to be withdrawn because of severe anemia. After three weeks, hemoglobin level rebounded to values higher than 10 g/dl and a lower dose of ribavirin (200 mg/tiw) could be reintroduced. Virological and biochemical response occurred after switching to standard interferon-alpha2b within three months with good tolerance of antiviral combination treatment until the end of 48 weeks of therapy. The patient remained HCV-RNA-negative throughout follow-up of 36 weeks. ALT levels are still within normal limits and the patient is now waiting for a kidney transplantation. CONCLUSION: Considering the treatment course of this patient, IFN-alpha2b three times per week directly after hemodialysis seems to be superior to pegylated interferon-alpha2b once weekly in this case. The role of pegylated IFN-alpha2a for dialysis patients remains to be investigated.

Adult↗
PubMed2004

[Hepatitis (Hep-Net) competence network].

In Germany almost 1 million people are affected by chronic viral hepatitis. Despite of the improved therapy options for the treatment of hepatitis B and C, several questions regarding epidemiology, pathophysiology and therapy are still unclear. Vaccines against hepatitis C and D viruses are still not available. Additionally, many patients and their relatives need information about infectiosity, course of the disease and therapy options. By the integration of doctors' practices and patient advocacy groups, Hep-Net aims at the educational information on the infection and tries to give access to qualified therapy strategies for all patients with an indication for therapy. After 18 months the Hep-Net Homepage already shows more than 9000 hits per day. Consultation hours via telephone, email-services and numerous activities in cooperation with the Deutsche Leberhilfe e.V. are highly frequented. In the Hep-Net study-house high-standard clinical studies with first successful results are centrally organized. Further, basic questions in the fields of epidemiology, virology and immunology are processed in cooperative research projects within the network.

Biomedical Research↗
PubMed2004

[Hepatitis as a travel disease].

Every year over 50 million people travel from industrialized countries to areas with high prevalence of oral-fecal and sexually transmissible forms of viral hepatitis. The risk of infection with hepatitis A is associated with the standard of living, the length of stay, and the area of destination. Acute hepatitis E is predominantly transmitted in India and other Asian countries. The main risk factors for the acquisition of hepatitis B are sexual promiscuity and unprotected sexual intercourse. This report provides detailed information on the risk of hepatitis in travelers, available vaccination schedules, clinical and laboratory diagnostic features, and necessary therapeutic aspects in cases of ongoing acute viral hepatitis.

Antiviral Agents↗
PubMed2004

Isolated anti-HBV core phenotype in anti-HCV-positive patients is associated with hepatitis C virus replication.

Recovery from hepatitis B virus (HBV) infection is associated with the presence of antibodies against HBV surface (HBs) antigen and HBV core (HBc) antigen. However, anti-HBs antibodies are lost in many cases, and only anti-HBc antibodies persist. A higher frequency of the anti-HBc-alone pattern has been demonstrated for anti-hepatitis C virus (HCV)-positive patients. In this report, 1126 anti-HCV-positive/anti-HBc-positive patients were studied, and the role of HCV replication in influencing the presence or absence of anti-HBs antibodies was investigated. The anti-HBc-alone phenotype was significantly more frequent in HCV-viraemic than in HCV-recovered patients. This finding represents new information regarding the immunopathogenesis of chronic HCV infection and supports previous data indicating impaired humoral immune responses in HCV infection.

Hepacivirus↗
PubMed2003

[Treatment of chronic hepatitis C with PEG-interferon alpha-2b and ribavirin: 24 weeks of therapy are sufficient for HCV genotype 2 and 3].

Patients with chronic hepatitis C infected with HCV genotype 2 and 3 can be successfully treated in more than 80 % of cases. It had been shown that a 24 week t.i.w. treatment period with standard interferon alpha and ribavirin is sufficient for these patients. However, the recent multicenter studies investigating the effect of pegylated interferons and ribavirin used a 48 week schedule for all patients irrespective of the HCV genotype. Thus, we prospectively investigated the efficacy of a 24 week treatment period with pegylated interferon alpha-2b (1.0-1.5 microg/kg o.i.w.) and ribavirin (1-1.2 g daily) in 54 patients with HCV-genotype 2 and 3 at two different sites. 29 patients were included in Herne (private practice) and 25 patients were treated in Hannover (Medical School). After the end of follow-up 46 (85%) patients showed a virological sustained response in the intent to treat analysis. Only four patients demonstrated a virological treatment failure (3 relapse, 1 breakthrough), two patients were non-compliant, and at each center therapy was stopped in one patient due to adverse events. There was no difference regarding treatment response between both sites, even though the patients in Herne were treated only with 1,0 microg/kg PEG-IFN alpha-2b, while patients in Hannover received 1,5 microg/kg PEG-IFN alpha-2b. In conclusion, the response rates of this study do not differ from the results of the 48 week treatment period of the recently published multicentre trials. Thus, we suggest treating all patients with HCV-genotype 2 and 3 for only 24 weeks when PEG-IFN alpha-2b is used in combination with ribavirin.

Adolescent↗
PubMed2003

Acute CMV-colitis in a patient with a history of ulcerative colitis.

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.

Acute Disease↗