HISTOLOGIC PROGRESSION OF RECURRENT HEPATITIS-C IN LIVER-TRANSPLANT ALLOGRAFTS

The incidence and severity of recurrent hepatitis C virus (HCV) infect ion in liver transplant recipients vary widely, and the long-term sequ elae of recurrent infection are not known. To better define the biolog y of recurrent HCV in liver transplant patients, we reviewed the histo logy of recurrent HCV in serial biopsies of 19 patients with pretransp lant polymerase chain reaction (PCR) evidence of HCV infection. All po sttransplant (post-TX) biopsies (n = 81) were reviewed, and RNA was ex tracted 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 albu min (as an internal control). All post-TX biopsies tested (12-1,677 da ys post-TX) were positive for HCV RNA by RT-PCR, while normal control biopsies were negative. Fifteen of 19 patients developed recurrent chr onic hepatitis typical of HCV. Many of these patients showed a progres sion from early biopsies with acute lobular hepatitis to later biopsie s with chronic hepatitis with portal lymphoid aggregates. An acute lob ular 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-he patitis biopsies was significantly different (p < 0.0004, Student's t test). Chronic hepatitis with portal lymphoid aggregates was seen an a verage of 356 days post-TX, with a range of 89-1,365 days. The time po st-TX was significantly longer than for acute lobular hepatitis (p < 0 .03, Student's t test). Fifty-three percent of HCV TX patients progres sed from acute lobular hepatitis to chronic hepatitis with lymphoid ag gregates within 1 year of TX, and 79% showed these changes within 4 ye ars. Six patients had progressive fibrosis; one died of liver failure and two became cirrhotic. Recurrent HCV appears to progress from an ac ute lobular hepatitis to chronic hepatitis with lymphoid aggregates in the majority of patients. Significant scarring occurred in 32% of pat ients and 16% developed end-stage liver disease from recurrent HCV. Th ese later findings suggest that the long-term course of recurrent HCV in liver allografts may not be as indolent as first thought.