First case report of an acute hepatitis E subgenotype 3c infection during pregnancy in Germany.

Hepatitis E is usually a self-limiting disease and an important cause of acute hepatitis in endemic countries in Asia and Africa. However, the mortality rate for pregnant women infected with hepatitis E virus (HEV) in this area is about 25%. In Germany, sporadic cases of acute hepatitis E infections have been described and the number of autochthonous infections is increasing. Here we report an autochthonous HEV subgenotype 3c infection in a 27-year old pregnant woman. This is the first documented case of a hepatitis E infection during pregnancy in Germany. The patient presented in week 26 of gestation with acute hepatitis and elevated transaminases. During follow-up, she tested positive for anti-HEV antibodies. HEV viral load during the acute hepatitis was 2.3×10(6) copies/ml serum, however viremia declined and cleared rapidly. Sequence analysis revealed a HEV subgenotype 3c closely related to European isolates. The patient had not travelled outside Germany, had regular contact to animals, but the source of infection remains unclear. The newborn was delivered in week 40 of gestation in good health, HEV was not transmitted and liver enzymes were normal. In conclusion, hepatitis E should be considered in differential diagnosis in patients with acute hepatitis especially during pregnancy, even without travel history to countries with high endemicity.

Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?

Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients. T cell stimulation has been induced by anti-CD3/anti-CD28 antibodies or by phorbol myristate acetate (PMA)/ionomycin. T cell proliferation was analysed by tritiumthymidine incorporation. Cell cycle progression was determined by propidium iodide staining using fluorescence activated cell sorter (FACS) analysis and by RNAse protection assay (RPA). Cytokine levels were assessed by enzyme-linked immunosorbent assay. T cell proliferation was inhibited significantly by imatinib, due most probably to cell cycle arrest in the G1-phase. This was paralleled by inhibition in the expression of cyclin-dependent kinases 1 and 2 mRNA. The expression of CD25 in naive and memory T cells was decreased significantly by imatinib in activated T cells. Similarly, conversion from naive to memory T cells after T cell activation was impaired by imatinib. Imatinib did not influence interleukin-2 and tumour necrosis factor-alpha production but increased interferon-gamma production. These observed effects of imatinib were similar in T cells from AASV patients and from healthy individuals. Imatinib might be an alternative therapeutical option for AASV patients refractory to conventional therapy.