DETECTION OF HCV ANTIGENS AS A UNIQUE TOOL TO IDENTIFY HCV INFECTION OF LIVER GRAFT: RELEVANCE TO MANAGEMENT OF LIVER DISEASE.

Abstract

O31 Aims: Early recurrence of HCV disease in liver graft is often difficult to demonstrate by histology. HCV antigens (HCV-Ag) can be detected by immunohistochemistry. A correlation between the number of infected hepatocytes and the pattern of histological damage was previously shown in transplanted patients. Aim of this study was to evaluate the impact of HCV-Ag detection in the management of patients transplanted for HCV related disease. Methods: HCV-Ag were detected, on frozen sections, using a 4 steps IPx technique with FITC-conjugated human anti-HCV IgG. The % of infected hepatocytes was estimated. Between 1996 and 2003 177 frozen liver biopsies were obtained from 116 HCV-RNA positive patients, transplanted, at different times from OLT. Histology was coded as: hepatitis, rejection, other (steatosis, cholangitis, cholestasis, reperfusion damage) or undefined when rejection grade II-III was excluded and different patterns coexisted. Results: Number of biopsies (no.), number of positive biopsies (no.+, %) and median % of positive hepatocytes (m%) at different time intervals are reported in the table.FigureHCV positive hepatocytes were found in 46%, 79% and 63% of biopsies at the 3 time intervals. Both the higher number of positive biopsies and the higher median number of positive cells were observed when hepatitis was identified by histology. This was particularly true in the acute phase of reinfection (21-180 days from OLT). In patients with serial biopsies an increase was usually observed when the first biopsy was taken very early and a decrease (spontaneous or treatment induced) when the second was after 6 months. Quantitative HCV viremia at the time of biopsy was available in 56 cases. Result was under the cut off sensibility in 9 cases, all negative for tissue HCV-Ag. A correlation was found (r=0.45) in the whole series but wide discrepancies were observed in individual patients. Detection of HCV-Ag had no impact on clinical management until 20 days from OLT: no antiviral treatment was started, rejection was treated in all positive cases. Similarly, after six months, rejection was treated independently of HCV-Ag positivity, antiviral treatment was not avoided in HCV-Ag negative patients. The high number of infected hepatocytes prompted a final diagnosis of hepatitis, confirmed by follow up analysis, in 8 further patients between 21 and 180 days and interferon treatment was started in 3 cases. In the same period rejection was treated in 2 patients with more than 50% HCV-Ag positive hepatocytes, but follow up analysis turned diagnosis to hepatitis. Conclusions: HCV-Ag detection is a unique tool to directly demonstrate recurrence of HCV infection in liver grafts. We confirm a relationship between the pattern of liver damage and the number of infected hepatocytes in the first 6 months after OLT: during this period, when multiple pathogenic mechanisms more frequently coexist, its relevance for clinical decision making seems particularly high.