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Research Interests: Microbiology, Immunology, Medical Microbiology, Natural History, Medicine, and 15 moreHepatitis C, Humans, Hepatitis C Virus, Liver Transplantation, Antimicrobial chemotherapy, Recurrence, Clinical Sciences, Disease Progression, Cirrhosis, Liver Failure, Liver Disease, End Stage Liver Disease, Reoperation, Antiviral Therapy, and Pharmacology and pharmaceutical sciences
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Cells respond to tumour necrosis factor-α (TNF-α) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are... more
Cells respond to tumour necrosis factor-α (TNF-α) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are co-expressed in many tissues, but their relative contributions to cellular TNF responses is for most situations unknown.In patients with viral and non-viral inflammatory liver diseases serum
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Die Zulassung neuer, direkt antiviral wirkender Substanzen hat die Therapie der Hepatitis C in den letzten zwei Jahren revolutioniert. Eine dauerhafte Viruselimination und damit eine Ausheilung der Hepatitis ist je nach Genotyp,... more
Die Zulassung neuer, direkt antiviral wirkender Substanzen hat die Therapie der Hepatitis C in den letzten zwei Jahren revolutioniert. Eine dauerhafte Viruselimination und damit eine Ausheilung der Hepatitis ist je nach Genotyp, Vorbehandlung und Fibrosestadium bei mehr als 90% der Patienten möglich. Die Therapiedauer hat sich wesentlich verkürzt. Die Nebenwirkungen sind gering (gelegentlich Kopfschmerzen, Übelkeit, Müdigkeit, Durchfälle) und führen nur sehr selten zum Therapieabbruch. Insgesamt hat sich damit die Lage Betroffener deutlich gebessert.
Research Interests: Medicine and Gynecology
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Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce... more
Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4+ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4+ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4+ T-cell response among HBeAg+ chronic carriers, and no response in patients with anti-HBe+ chronic hepatitis. An increasing CD4+ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HB...
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Research Interests: Gastroenterology, Medicine, Hepatitis C, Multidisciplinary, Humans, and 15 moreFemale, Male, Hepatitis C Virus, Clinical Sciences, Middle Aged, Genotype, Adult, Combination drug therapy, Ns, Benzimidazoles, Neurosciences, Antiviral Agents, Hepacivirus, Paediatrics and reproductive medicine, and Pharmacology and pharmaceutical sciences
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Since the hepatitis B virus is noncytopathic, it is generally believed that the individual specific immune response determines the course of infection. The lack of data about hepatitis B virus-specific T-cell reactions in acute infection... more
Since the hepatitis B virus is noncytopathic, it is generally believed that the individual specific immune response determines the course of infection. The lack of data about hepatitis B virus-specific T-cell reactions in acute infection led us to investigate the specific cellular immune response of infected individuals in terms of proliferation, and gamma-interferon and lymphotoxin production. Our results demonstrate that peripheral blood mononuclear cells (PBMNC) from patients with acute and chronic hepatitis B respond weakly to HBsAg. In contrast, patients with acute hepatitis show a vigorous response to the nucleocapsid antigen (HBcAg) in terms of proliferation and lymphokine production, while only few chronic virus carriers gave a proliferative response. Either of the antigens could activate lymphocytes to produce gamma-interferon and lymphotoxin, cytokines which may modulate antiviral immune response.
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Research Interests: Virology, Medicine, Hepatitis C, Hepatology, Clinical Sciences, and 4 moreImmune system, CTL, Ns, and epitope
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Research Interests: Immunology, Biology, Histology, Infectious Diseases, Hepatitis C, and 15 moreBiopsy, Biological Sciences, Cell line, Humans, Liver, Female, Hepatitis C Virus, Infectious, Genotype, Graft Rejection, Enzyme Linked Immunosorbent Assay, Antigen, Interferon gamma, Hepacivirus, and Cell culture techniques
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Background/Aims: Pulmonary side effects of interferon-α therapy of chronic hepatitis C seem to be rare. So far, only two cases of sarcoidosis in association with interferon-α treatment of chronic hepatitis C have been... more
Background/Aims: Pulmonary side effects of interferon-α therapy of chronic hepatitis C seem to be rare. So far, only two cases of sarcoidosis in association with interferon-α treatment of chronic hepatitis C have been described.Methods/Cases: We report on three patients who were treated with recombinant interferon-α2a for chronic hepatitis C, two of them in combination with ribavirin. These patients developed pulmonary
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Zusammenfassung Eine 67-jährige depressive Patientin wird mit Vigilanzminderung und Hyponatriämie (105 mmol/l) aufgenommen. Als Ursache der symptomatischen Hyponatriämie findet sich ein Syndrom der inadäquaten ADH-Sekretion (SIADH) unter... more
Zusammenfassung Eine 67-jährige depressive Patientin wird mit Vigilanzminderung und Hyponatriämie (105 mmol/l) aufgenommen. Als Ursache der symptomatischen Hyponatriämie findet sich ein Syndrom der inadäquaten ADH-Sekretion (SIADH) unter Einnahme des selektiven Serotonin-Reuptake-Inhibitors (SSRI) Citalopram. Die Citalopram-Medikation wurde abgesetzt und die Hyponatriämie durch Flüssigkeitsrestriktion und Diuretikagabe langsam ausgeglichen. Angesichts des zunehmenden Einsatzes von SSRIs bei depressiven Patienten werden die Risikofaktoren dieser seltenen, jedoch potenziell
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Research Interests: Clinical Trial, Biology, Adolescent, Medicine, Hepatitis C, and 15 moreBiological Sciences, Humans, Female, Epitope mapping, Male, Antigen Presentation, Hepatitis C Virus, Adult, Amino Acid Sequence, chronic hepatitis C, Hepacivirus, alleles, Human leukocyte antigen, epitope, and Medical and Health Sciences
Virus-specific CD4(+) T-cell response at the site of inflammation is believed to play a decisive role for the course of viral disease. In hepatitis C virus (HCV) infection, the majority of studies focused on the peripheral blood T-cell... more
Virus-specific CD4(+) T-cell response at the site of inflammation is believed to play a decisive role for the course of viral disease. In hepatitis C virus (HCV) infection, the majority of studies focused on the peripheral blood T-cell response. In this study we analyzed intrahepatic virus-specific CD4(+) T-cell response and compared this with that in the peripheral blood. Liver and blood-derived T-cell lines were studied in 36 patients (18 with chronic hepatitis C and 18 with HCV-associated cirrhosis). Virus-specific interferon gamma (IFN-gamma) production at a single cell level to various HCV-proteins (core, nonstructural [NS] 3/4, NS5) were determined by enzyme-linked immunospot (ELIspot). Phenotyping was done by fluorescent-activated cell sorter analysis. In approximately half (16 of 36 [44%]) of intrahepatic T-cell lines a significant number of IFN-gamma spots were observed, whereas this was the case in only 19% (7 of 36 T-cell lines) in the blood. In relative terms, core and nonstructural proteins were recognized with the same frequency in both compartments, but HCV-specificity was significantly more often detected in liver tissue compared with the blood. Hepatitis activity index, viral load, and alanine transaminase levels did not correlate with the detection of HCV-specific CD4(+) T cells. All T-cell lines were dominated by CD4(+) T cells. In conclusion, HCV-specific CD4(+) T cells are multispecific, compartmentalize to the liver, and produce IFN-gamma. We speculate that our data would support the concept of compartmentalization of specific T cells at the site of inflammation and that a low frequency of specific T cells is associated with failure to clear the virus and a chronic course of disease.
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Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study... more
Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known histo...
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Recurrent hepatitis C virus infection after liver transplantation: natural course, therapeutic approach and possible
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Recurrence of hepatitis C virus during leucocytopenia and spontaneous clearance after recovery from cytopenia: a case report
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T cells are believed to be the main players in antiviral defence. To investigate the role of the specific CD4+ T cell response for clearance and control of the hepatitis C virus we studied patients with acute hepatitis C (AHC) during the... more
T cells are believed to be the main players in antiviral defence. To investigate the role of the specific CD4+ T cell response for clearance and control of the hepatitis C virus we studied patients with acute hepatitis C (AHC) during the phase of spontaneous viral clearance and during follow up after elimination of the virus and resolution of disease. Symptomatic AHC has a self‐limited course in 50% of patients, whereas the other half show virus persistence and develop chronic course of disease. Patients who were able to mount a vigorous, polyclonal, multispecific, TH1 lymphokine dominated CD4+ T‐cell response showed viral clearance and a self‐limited course of disease. In contrast, absence of this T‐cell response in patients with AHC invariably led to viral persistence and chronic hepatitis. The characteristics of the T‐cell response were as follows: it was mainly directed against nonstructural proteins of the virus, it was multispecific and demonstrated immunodominant epitopes, an...
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Research Interests: Genetics, Biology, Virology, Hepatology, Mutation, and 3 moreInterferon, Clinical Sciences, and stop codon
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The impacts of viral load, genotype, age, sex and BMI on the clinical course of acute hepatitis C are poorly defined. Here we studied 259 patients with acute HCV infection recruited in the German Hep-Net data base between 1998 and 2008.... more
The impacts of viral load, genotype, age, sex and BMI on the clinical course of acute hepatitis C are poorly defined. Here we studied 259 patients with acute HCV infection recruited in the German Hep-Net data base between 1998 and 2008. Antiviral treatment with interferon alpha was initiated in 171 patients (66 %) within 4 months after the diagnosis of acute hepatitis C. In this cohort (i) the mode of infection was associated with age as iv-drug users were significantly younger than non-iv-drug users while the proportion of patients who acquired HCV by medical procedures increased with age; (ii) patients younger than 30 years were more often infected with genotype 3 (26 % versus 8 % for patients older than 50 years; p = 0.03); (iii) 51 % of patients were icteric and 28 % presented with a 30-fold elevation of liver enzymes, however, no fulminant hepatic failure occurred; (iv) HCV genotype was not associated with disease severity and time to onset of symptoms; (v) low HCV viremia was associated with lower serum AST levels and a longer time from exposure to onset of symptoms; (vi) disease severity was independent from the mode of infection, age, sex and body mass index (BMI). In this large cohort of patients admitted for antiviral therapy, acute hepatitis C took a rather mild course of disease in the majority of patients. Disease severity was not associated with HCV genotype, viral load, age, sex and BMI.
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CD41 T cells play a major role in the host defense against viruses and intracellular microbes. During the natural course of such an infection, specific CD41 T cells are exposed to a wide range of antigen concentrations depending on the... more
CD41 T cells play a major role in the host defense against viruses and intracellular microbes. During the natural course of such an infection, specific CD41 T cells are exposed to a wide range of antigen concentrations depending on the body compartment and the stage of disease. While epitope variants trigger only subsets of T-cell effector functions, the response of virus-specific CD41 T cells to various concentrations of the wild-type antigen has not been systematically studied. We stimulated hepatitis B virus core- and hepatitis C virus NS3-specific CD41 T-cell clones which had been isolated from patients with acute hepatitis during viral clearance with a wide range of specific antigen concentrations and determined the phenotypic changes and the
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Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. We... more
Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly ass...