22 Our results would also suggest a role of cell-to-cell transmission during the first days following graft infection: the presence of high levels of claudin-1 and occludin might facilitate HCV spread within the liver, resulting in a faster increase in HCV-RNA concentrations. It is clear that other variables not analyzed in this study (such as HCV fitness, quasispecies evolution) may also play a role in early HCV kinetics. Our study has some limitations.
First, the study is retrospective in its design and preservation of liver samples may not have been completely homogeneous across the study period. Second, liver tissue obtained before HCV infection (reperfusion liver biopsies) cannot be considered
selleck chemicals normal, because samples are obtained Metformin molecular weight from the liver of a deceased donor after treatment of the organ with a preservation solution. Finally, patients undergoing LT are treated with immunosuppression drugs, which may influence the expression of HCV receptors. In summary, hepatitis C recurrence after LT is associated with increased levels of claudin-1 and occludin in hepatocyte membranes, although this does not alter their localization or expression pattern within the tight junctions. HCV receptor levels at the time of LT seem to modulate early HCV kinetics, which may be relevant when designing strategies to prevent HCV infection in the graft. Cetuximab Additional supporting information may be found in the online version of this article. “
“Conventional creatinine-based glomerular
filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by nonradiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the “bias,” “precision,” and “accuracy” of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG), and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores (differences between mGFR and estimated GFR [eGFR] or between mGFR and CrCl, or between mGFR and CG equation for each subject) (RMSE = 23.56) was significantly better than that of CrCl (37.69, P = 0.001), CG (RMSE = 36.12, P = 0.002), and GFR-estimating equations based on cystatin C only.