The aim of this exploratory study was to determine whether inflammatory proteins and/or miRNA in serum specimens collected near the time of protocol or for cause biopsies at different intervals after transplantation, can provide information on the status of the liver. Specifically, whether serum assays are correlated with the severity of HCV reactivation, and differentiate HCV from acute cellular rejection.

Methods: A total of 210 serum samples from 72 recipients participating in the A2ALL study were available. Of these, 58 samples were taken at for-cause biopsy. Pathology results of the biopsies were confirmed at the A2ALL pathology core. There were 43 pre- and 109 post-biopsy serum samples available. Serum samples were analyzed for a 48 protein inflammatory panel, and 1718 human miRNA sequences. Pairs of conditions were specified for analysis. The P-values were calculated by T test and corrected for multiple testing by Benjamini-Hochberg step up method.

Results: I. Peripheral inflammatory protein and miRNA profiles were significantly different between HCV and non-HCV recipients at any time after transplantation (table 1). II. Severe HCV activity at for-cause biopsy (histology activity index >7) was associated with higher levels of MCP-1, Eotaxin-1(P=0.02), and mild elevation of miR-193a-5p (p=0.09). These findings were present prior to, and after biopsy (table 2). III. Acute rejection was differentiated from severe HCV recurrence by higher levels of IL-23 and A-2-macroglobulin, and the expression of miR-774 and miR-92b (p<0.008) (table 2).

Conclusions: The severity of HCV activation and the findings of acute rejection are differentiated by proinflammatory proteins and miRNA profiles in the periphery. These findings suggest that peripheral biomarkers may be used to confirm post-transplant liver pathology without the need for biopsy.

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