Histologic Progression of Recurrent Hepatitis C in Liver Transplant Allografts

Abstract

The incidence and severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients vary widely, and the long-term sequelae of recurrent infection are not known. To better define the biology of recurrent HCV in liver transplant patients, we reviewed the histology of recurrent HCV in serial biopsies of 19 patients with pretransplant polymerase chain reaction (PCR) evidence of HCV infection. All posttransplant (post-TX) biopsies (n = 81) were reviewed, and RNA was extracted from at least one paraffin-embedded biopsy from each patient. RNA was analyzed for HCV by nested, reverse transcription-PCR (RT-PCR) using primers for the 5' non-coding region of HCV as well as for albumin (as an internal control). All post-TX biopsies tested (12-1,677 days post-TX) were positive for HCV RNA by RT-PCR, while normal control biopsies were negative. Fifteen of 19 patients developed recurrent chronic hepatitis typical of HCV. Many of these patients showed a progression from early biopsies with acute lobular hepatitis to later biopsies with chronic hepatitis with portal lymphoid aggregates. An acute lobular hepatitis typified by sinusoidal lymphocytosis, acidophil bodies, and lobular disarray was seen an average of 135 days post-TX, with a range of 39-279 days. The time post-TX between this and earlier non-hepatitis biopsies was significantly different (p < 0.0004, Student's t test). Chronic hepatitis with portal lymphoid aggregates was seen an average of 356 days post-TX, with a range of 89-1,365 days. The time post-TX was significantly longer than for acute lobular hepatitis (p < 0.03, Student's t test). Fifty-three percent of HCV TX patients progressed from acute lobular hepatitis to chronic hepatitis with lymphoid aggregates within 1 year of TX, and 79% showed these changes within 4 years. Six patients had progressive fibrosis; one die of liver failure and two became cirrhotic. Recurrent HCV appears to progress from an acute lobular hepatitis to chronic hepatitis with lymphoid aggregates in the majority of patients. Significant scarring occurred in 32% of patients and 16% developed end-stage liver disease from recurrent HCV. These later findings suggest that the long-term course of recurrent HCV in liver allografts may not be as indolent as first thought.