We appreciate the observations made by Harris et al. regarding the differences in claudin-1 expression in human liver between the report by Reynolds et al.1 and our work.2 The main objective of our study was to assess the potential changes in tight junction proteins claudin-1 and occludin following hepatitis C virus (HCV) graft infection. We observed an increased expression of claudin-1 and occludin over time in HCV-infected patients. The increase in claudin-1 was particularly significant in individuals with cholestatic hepatitis. It is important to notice that when we applied very low threshold values to create a surface for quantification, it was almost impossible to discriminate basolateral claudin-1 staining from either unspecific staining or tissue autofluorescence. More restrictive thresholding guarantees the quantification of specific signal, although it should be noted that this is at the expense of decreased sensitivity. Thus, it is a possibility that we may have underestimated claudin-1 expression in the basolateral membrane because we quantified fluorescence intensity using a single threshold value.
The detection of minor pools of basolateral claudin-1 is an interesting finding. Further studies are required to investigate the role of nonjunctional claudin-1 in HCV entry and the physiopathological consequences of increased levels of claudin-1 expression in HCV disease progression.