Autoimmune Lebererkrankungen

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Merging models of hepatitis C virus pathogenesis

Chronic hepatitis C virus (HCV) infection is one of the major causes for development of liver cirrhosis and end-stage liver disease. This article reviews two contrasting models of HCV pathogenesis, discusses the merits of each, and presents a rationale for combining the two models into one. Any successful model of HCV pathogenesis must explain how the characteristic features of cirrhosis and end-stage liver disease arise. These features include the loss of hepatocyte function (low serum albumin and reduced clotting ability); the presence of regenerative nodules; and the deposition of excessive extracellular matrix material, especially collagen (fibrosis), which is associated with the transformation of the liver sinusoids to capillary-like structures leading to portal hypertension. A successful model should explain several observations about the rate of disease progression. HCV is characterized by slow progression of fibrogenesis and, importantly, cirrhosis seems to develop only after a long latency (and only in a subset of patients). Among the prognostic factors of disease progression, the age at infection with the HCV virus and the presence of fibrosis appear to be highly relevant in predicting the development of progressive fibrosis. Traditional models of HCV pathogenesis propose that fibrogenesis is the predominant process. Fibrogenesis is induced by activation of fibrogenic cells, such as stellate cells, which results in excessive collagen deposition. By altering the normal architecture and vasculature, the collagen bands finally lead to cirrhosis and loss of organ function. Activation of stellate cells is induced by inflammation, cytokine signaling, and possibly by hepatocyte apoptosis. The telomere model of HCV pathogenesis suggests that hepatocyte damage plays an essential role in the development of cirrhosis. According to this model, hepatocyte damage leads to increased cell turnover, and to the accelerated shortening of hepatocyte telomeres. Critical telomere shortening leads to hepatocyte senescence, loss of hepatocyte function, exhaustion of hepatocellular regeneration, and to a greatly enhanced fibrotic response to injury. This review summarizes both models and presents evidence that these models are not mutually exclusive but rather can be merged into a comprehensive pathogenesis model that outlines the pathway of HCV-induced cirrhosis.     

Candidemia in Norway (1991 to 2003): results from a nationwide study

A long-term, nationwide prospective candidemia study has been ongoing in Norway since 1991. All medical microbiological laboratories in the country have participated. During the period 1991 to 2003 a total of 1,393 episodes of candidemia occurred in 1,348 patients. The incidence of candidemia episodes per 100,000 inhabitants increased from approximately 2 episodes in the early 1990s to 3 episodes in 2001 to 2003. The average annual incidences varied markedly between the age groups. The incidence was high in patients aged < 1 year and in patients aged > or = 70 years. In patients > or = 80 years of age, the incidence has increased during the last 3 years from an annual average of 6.5 to 15.6 cases/100,000 inhabitants in 2003. Four Candida species (C. albicans [70%], C. glabrata [13%], C. tropicalis [7%], and C. parapsilosis [6%]) accounted for 95.5% of the isolates. The species distribution has been constant during the 13-year study period. The distribution of the most important species varied with the age of the patient. In patients < 1 year of age, the majority of episodes were caused by C. albicans (91%). The occurrence of C. glabrata increased with age. In patients > or = 80 years of age, approximately 1/3 of all episodes were due to this species. All C. albicans strains were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs > or = 16 microg/ml) was 10.7% during the first period of this study (1991 to 1996) and 11.7% during the second period (1997 to 2003).     

Performance and clinical utility of a novel fully automated quantitative HCV-core antigen assay

BackgroundRecently, a novel quantitative HCVcoreAg immunoassay developed for commercialisation by Abbott has become available in Europe and Asia.ObjectivesWe evaluated the correlation of HCV-RNA and HCVcoreAg and investigated the stability of HCVcoreAg and HCV-RNA.Study designHCVcoreAg was quantified by a novel fully automated immunoassay (Architect HCVAg, Abbott, Germany). HCV-RNA quantification was performed either using the Cobas-TaqMan assay or Amplicor-HCV-Monitor (Roche-Diagnostics, Germany). Correlation of HCVcoreAg with HCV-RNA was studied cross-sectionally and longitudinally in untreated patients followed for up to 8 years. Stability of HCVcoreAg and HCV-RNA was evaluated in plasma and whole blood stored for up to 96 h at different conditions.ResultsHCVcoreAg showed good correlation with HCV-RNA in all 118 cross-sectional tested samples irrespective of the HCV genotype (r = 0.75). In the majority but not all of the 10 longitudinally studied patients HCVcoreAg also demonstrated a good correlation with HCV-RNA. HCVcoreAg was stable in plasma at 4, 20, and 37 °C for up to 96 h, whereas HCV-RNA significantly declined at 37 °C. In whole blood, HCVcoreAg and HCV-RNA levels declined at all conditions with exception of HCVcoreAg at 37 °C. HCVcoreAg was stable after 1–5 freezing/thawing cycles and not light-sensitive.ConclusionsHCVcoreAg represents a stable and reliable marker of viral replication showing a good correlation with HCV-RNA irrespective of the HCV genotype. HCVcoreAg determination can be used to confirm viral replication and monitor viral load or acquisition of HCV over time.