Characterization of CD4, CD8, CD56 positive lymphocytes and C4d deposits to distinguish acute cellular rejection from recurrent hepatitis C in post-liver transplant biopsies

Introduction: Hepatitis C viral (HCV) infection is the most common cause for liver transplantation (LTx) in USA. Hepatitis C viral recurrence in liver allograft is almost universal, which is often difficult to distinguish from acute cellular rejection (ACR). Aim: Aim of the present study is to examine the differences between distribution of CD4, CD8, CD56 positive lymphocytes, and C4d deposits in patients with ACR and recurrent HCV. Patients and methods: As a pilot project, a group of five post-LTx HCV RNA negative patients, strongly suspicious for ACR based on clinical findings and history of medication non-compliance and another group of five post-LTx HCV positive, medication compliant patients with abnormal liver function were retrospectively selected. Liver biopsies of these patients were stained with monoclonal CD4, CD8, CD56, and polyclonal C4d antibodies and compared. Results: Mean CD4, CD8, and CD56 counts in ACR group were 156.7 +/- 17.6, 35.4 +/- 8.8, and 1.0 +/- 1.8/HPF, respectively and were 89.7 +/- 41.3, 20.3 +/- 23.2, and 0.6 +/- 0.9/HPF, respectively in HCV recurrence group. Biopsies of four of five patients with ACR demonstrated moderate to strong C4d staining, whereas all patients with recurrent HCV had none to mild C4d staining. Conclusion: Mean CD4, CD8, and CD56 were similar for acute rejection and recurrent HCV infection. However, 80% of patients with ACR showed moderate to strong staining for C4d and all recurrent HCV patients showed none to mild C4d staining.