Analysis of Liver Transplant Outcomes using a Cluster of Differentiation
Antibody Array.
Background: Hepatitis C virus (HCV)-related end-stage liver disease is a primary indication
for liver transplantation. At present, severe HCV recurrence is poorly determined by liver
biopsies and viral load. Non-invasive means of predicting severe recurrence are required. CD
antibody microarrays, which use a live cell-capture technique, enable a semi-quantitative
leucocyte immunophenotype. We have previously used this assay to demonstrate disease
specific consensus patterns of expression of CD antigens for patients with chronic liver
disease including hepatitis C virus (HCV) infection.
Aims: To determine CD antigen expression profiles for patients undergoing liver
transplantation for active HCV infection looking for preserved disease-specific signatures
predictive of outcomes.
Methods: Sixteen consecutive HCV liver transplant patients were recruited for this study.
The average MELD was 17.3(12-29). Serial assays where performed during the Pretransplant (day0), Early (d3–week2), Mid (w4-w10), and Late (>w12) phases. Four different
definitions for HCV recurrence severity were used based on protocol liver biopsies and peak
HCV viral load. Differential expression analysis was performed to assess for time points of
greatest change and significant antibodies.
Results: Four separate classifications for severe HCV recurrence where examined based on
the outcome in the first 2 years post transplant (severe vs. mild); 1) F3-4 fibrosis vs. F≤2 , 2) F24 fibrosis vs. F<2, 3) F3-4 vs. Mild F<2 (excluding F=2) and 4) Peak viral load >107vs. ≤107. The
greatest differential antibody expression was seen in the Pre-transplant phase (d0),
irrespective of the definition used for severe HCV recurrence. Significant antibodies
expressed across all HCV recurrence definitions include the T-cell activation molecule CD27,
CD182, CD260, and CD34. CD81, which is known to mediate HCV cellular entry, was
significantly expressed in 3 of 4 definitions. A single antigen, CD152, was predictive of
severe recurrence irrespective of the classification in the late phase of sampling (>w12).
Conclusion: These results demonstrate that the pre-transplant CD antigen expression profile
is the greatest determinant of recurrent HCV disease severity post-liver transplantation.
Further assessment of pre-transplant factors is required to develop tests predictive of severe
HCV recurrence.