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Biomedical subjects

H L Tillmann

Publications and source records attributed to H L Tillmann.

At least 19 recordsLinked to original sources
PubMed2007

[Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis].

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome. Since the prevalence of obesity and consequently of the metabolic syndrome is steadily increasing, the different types of NAFLD are nowadays the most common cause of liver injury in North America. The development of NASH and fatty liver cirrhosis occurs after a "two-hit-theory", in which hepatic steatosis is followed by lipid peroxidation, the production of cytokines and the induction of Fas ligand. A standardized drug based therapy does not exist so far, but glitazones have emerged as a promising treatment option. However, since the disease is related to Western lifestyle, treatment should be based on prevention and changes in lifestyle.

Fatty Liver↗
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

Low prevalence of chronic hepatitis C, but high prevalence of elevated aminotransferases in a cohort of 2026 patients referred for orthopaedic surgery in the eastern part of Germany.

INTRODUCTION: The prevalence of chronic hepatitis C in Germany is about 0.2 - 0.4 %. However, there seems to be regional differences between western and eastern states of the country. Thus, the present study analysed the prevalence of chronic hepatitis C in a cohort of orthopaedic patients in Thuringia. METHODS: Tests for antibodies against hepatitis C virus (anti-HCV) were performed on serum samples of 2026 patients (1183 females, 843 males) admitted for orthopaedic surgery to a university hospital in Thuringia. If anti-HCV was positive, serum was tested for HCV-RNA by polymerase chain reaction (PCR). For the sake of anonymity only age and gender were reported in all patients. In 1465 cases, values of alanine (ALT) and aspartate (AST) aminotransferases were additionally available. The low HCV prevalence was confirmed in a second cohort of orthopaedic patients (n = 929, 599 females, 330 males) investigated at a university hospital in Saxonia. RESULTS: In the Thuringian cohort, anti-HCV was detectable in 12/2026 (0.6 %) individuals (10 females (0.85 %) and 2 males (0.24 %: p = 0.14 %). HCV-RNA was positive in 3/10 of anti-HCV positive females (0.15 % of the study cohort). HCV infection was already known in two cases. Anti-HCV positive patients seemed to be older than anti-HCV negative individuals (64.25 vs. 59.48 years; p = 0.17), as well as HCV-RNA positive cases compared to non-viraemic patients (66.3 vs. 63.6 years; p = 0.32). All HCV-RNA positive females had elevated ALT values. However, ALT and AST were also elevated in 18.2 % and 11.7 % of anti-HCV negative individuals. There was no significant difference between males and females (p = 0.32). In the Saxonian cohort none of 929 individuals were HCV positive. CONCLUSION: The prevalence of chronic hepatitis C is low in the investigated cohorts of orthopaedic patients in Thuringia and Saxonia. However, elevation of aminotransferases occurs surprisingly often. The reasons for elevated aminotransferases and a reliable analysis of the HCV prevalence in different subgroups of the Eastern German population require further evaluation.

Cohort Studies↗
PubMed2006

Coexistence of autoimmune pancreatitis and primary biliary cirrhosis in a Caucasian patient - a rare cause of cholestasis.

In contrast to Asia, autoimmune pancreatitis is rare in the Western population. The present case report describes the coexistence of primary biliary cirrhosis and autoimmune pancreatitis accompanied by sclerosing cholangitis of the intrahepatic bile ducts and the hilar region. It is important to differentiate sclerosing cholangitis due to autoimmune pancreatitis from primary sclerosing cholangitis and primary biliary cirrhosis, because the former responds to steroids, while the latter do not. The article highlights important diagnostic difficulties and suggests racial differences between Caucasian and Asian patients.

Autoantibodies↗
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

Effect of early and late GB virus C viraemia on survival of HIV-infected individuals: a meta-analysis.

OBJECTIVES: To conduct a meta-analysis to synthesize the evidence regarding the effect of co-infection with GB virus C (GBV-C) on survival of HIV-infected individuals, and to estimate the effect. METHODS: A Bayesian meta-analysis was conducted to synthesize evidence from eligible studies. Prospective survival studies of HIV-1-infected individuals, with outcome defined as time from baseline to all-cause death, were included and classified by whether GBV-C status was determined in early or late HIV disease. The primary measure was the hazard ratio (HR) of death for HIV-infected individuals with GBV-C infection versus those without GBV-C infection. RESULTS: Eleven studies from eight publications met the inclusion criteria. For studies with GBV-C status measured 2 years or less after HIV seroconversion (912 subjects), the combined HR was 0.88 [95% credible interval (CI) 0.30, 1.50]. For studies with GBV-C status measured more than 2 years after HIV seroconversion (1294 subjects), the combined HR was 0.41 (95% CI 0.23, 0.69). CONCLUSIONS: No conclusive evidence was found of an association between survival and GBV-C infection early in HIV disease. However, when GBV-C infection was present later in HIV disease, a significant reduction in the hazard for mortality was observed for those with co-infection. Potential explanations for this difference include a non-proportional benefit of GBV-C over time, possibly related to clearance of GBV-C infection early in HIV disease. The timing of GBV-C infection appears to account for the contradictory results of studies on the effect of GBV-C coinfection on survival of HIV-infected people.

Adult↗
PubMed2005

[Severe intrahepatic cholestasis in a 66-year old male patient with medically treated atrial fibrillation].

A 66-year-old male was admitted to hospital due to painless jaundice. Because of ischemic cardiomyopathy with paroxysmal atrial fibrillation as well as recurrent ventricular tachycardias and fibrillation he was treated with phenprocoumon and amiodarone (200 mg per day) for 2 years. Laboratory tests revealed significant elevation of the parameters of cholestasis and aminotransferase activity. Serological tests excluded infectious, autoimmune or metabolic liver diseases. Abdominal ultrasound and ERCP showed no mechanic cholestasis nor tumor of the pancreas. Cardiac congestive disease was also excluded. Severe intrahepatic cholestasis, consistent with drug-induced hepatotoxic damage, was diagnosed histologically. After discontinuing phenprocoumon the liver enzymes further increased. When amiodarone was stopped, however, laboratory parameters showed a continuous downward tendency. For prevention of malignant cardiac arrhythmia the patient received an atrioventricular defibrillator. Intrahepatic cholestasis is a rare presentation of amiodarone-induced hepatic toxicity. Liver damage can even occur after the drug has been taken for prolonged periods without any problems.

Aged↗
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

Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated.

INTRODUCTION: Lamivudine is a treatment option for the therapy of chronic hepatitis B with an excellent safety profile. Unfortunately, viral resistance to lamivudine is common in the course of therapy. The lamivudine resistant mutants are usually less pathogenic than the wild type, but development of viral resistance can also lead to acute exacerbation of the underlying hepatitis. The recently FDA approved nucleoside analogue adefovir dipivoxil has potent antiviral activity against lamivudine-resistant mutants and can prevent viral replication effectively. CASE REPORT: A 31-year-old man with pre-existing compensated liver cirrhosis developed resistance to lamivudine therapy leading to subacute liver failure. After referral adefovir dipivoxil 10 mg daily was initiated within an early access protocol. Since initiating therapy with adefovir dipivoxil progression of the subacute liver failure was delayed accompanied by a rapid decrease of ALT and decline of HBV viral load. Even so, the clinical course was not reverted but showed slower deterioration. This enabled the patient to undergo living-related liver transplantation. Adefovir dipivoxil was well tolerated in the acute phase of the disease and did not cause nephrotoxicity or favour the development of hepatorenal syndrome. CONCLUSION: Adefovir dipivoxil resulted in a delay of hepatic decompensation and enabled liver transplantation as final treatment option for this patient. Earlier initiation might even have prevented the need of liver transplantation. Thus, in patients with pre-existing liver cirrhosis an early switch to adefovir dipivoxil appears indicated after emergence of lamivudine resistance.

Adenine↗
PubMed2004

GB virus C infection and quality of life in HIV-positive patients.

It was recently shown that GBV-C infection is associated with prolonged survival of HIV-infected individuals. The GB virus C is the closest known relative of hepatitis C virus in man. The latter has been associated with significant impairment in quality of life, independent from the associated liver disease. We were thus interested in the impact of GB virus C infection on quality of life in HIV-infected individuals. We retrospectively analyzed a cohort of HIV-positive patients who previously answered the 'HIV-SELT' and the 'EQ-5D' questionnaires assessing quality of life and for whom data on GB virus C RNA status were available. In this study we identified no adverse effect of GB virus C on quality of life, but, in contrast, GB virus C viraemic patients showed better quality of life in all parameters for the scores in comparison to GB virus C-negative HIV-infected patients. HIV-positive patients with a GB virus C infection showed superior quality of life. These data further support the favourable course of HIV disease in GB virus C-positive patients.

Adult↗
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

[Virus associated glomerulonephritis].

Virus associated glomerulonephritis is considered to be a para- or post-infectious autoimmune phenomena. The disease is mediated by immune complexes which usually contain the viral antigen. Virus associated glomerulonephritis due to chronic viral infection with hepatitis B or C virus, or with human immunodeficiency virus (HIV) shows a typical histomorphological picture for each virus. Hepatitis B virus usually leads to a membranous glomerulonephritis, while hepatitis C virus is associated with a membranoproliferative glomerulonephritis due to cryoglobulins, and HIV is associated with a focal segmental sclerosing glomerulonephritis. Knowledge of the relationship between the primary viral infection and secondary glomerulonephritis is important, as a primary immunosuppressive therapy might lead to more severe viral disease. On the other hand, a primary reduction in the viral load due to antiviral therapy with immunostimulants or inhibitors of viral replication could lead to an amelioration of the secondary glomerulonephritis.

Antiviral Agents↗