Hepatic Progenitor Cells

Abstract

Purpose: HCV is the most common indication for liver transplantation (LT). The cholestatic variant of HCV (cvHCV) is characterized by rapid HCV progression leading to graft loss. Older donor age is associated with aggressive disease and rapid fibrosis progression. Ductular reaction (DR), believed to arise from hepatic progenitor cells (HPC) is associated with hepatic fibrosis. The aims of this study are (1) to demonstrate the HPC count and DR in the following three clinical outcomes of recurrent HCV: stable histology (no > stage 2 of 4 fibrosis), cirrhosis, and cvHCV and (2) to demonstrate the association between HPC, DR, and donor age. Methods: Using the LT database, a search for HCV cases from 1992–2007 yielded 903 cases, in which 203 had donor age >60 yrs and 195 donor age <30 yrs. Cases of re-LT, living donor LT, HIV, CMV, HBV co-infection, concurrent bile duct problem, and rejection were excluded. Liver biopsies (bx) from time of LT (pre- and post-perfusion) and serially thereafter were reviewed by a liver pathologist (MIF). Sections from paraffin blocks were immunostained with CK7 delineating HPC and bile ductules. Five portal/periportal areas were inspected for HPC (via manual cell count) and photographed at 200× magnification and were analyzed by a novel image analysis technique that calculated DR as% area with (+) CK7 stain. Results: 21 cases of stable histology (11 with donor age >60 yrs, 10 with donor age <30), 21 cases of cirrhosis (11 with donor age >60 yrs, 10 with donor age <30), and 10 cases of cvHCV (8 with donor age >60 yrs, 2 with donor age <30) were identified. There was no significant relationship for HPC count or DR at baseline bx between all outcome groups and donor age. At bx showing initial recurrent HCV, mean HPC count for the cirrhosis group (4.6) was greater than both the stable (1.9) and cvHCV (1.3) groups (P < 0.05); DR for the cirrhosis group (3.2%) was greater than the stable (1.4%, P < 0.05) and cvHCV group (1.7%, P= NS). At endpoint bx, HPC count was higher in the cvHCV (5.3) vs. stable (0.93, P < 0.05) and cirrhosis (3.9) vs. stable (P < 0.05) groups. Mean DR for the cvHCV, cirrhosis, and stable groups were 6.4%, 3.4%, 1.4%, respectively (P < 0.05). At endpoint bx, DR was significantly higher in all bx for donor age >60 yrs (3.8%) when compared to endpoint bx with donor age <30 yrs (2.4%, P= 0.009). Conclusion: There are no differences in HPC count and DR in pre- and post-perfusion bx at time of LT. At initial bx showing recurrent HCV, the cirrhosis group showed increased HPC counts and DR, whereas the cvHCV and stable groups did not. At endpoint bx the HPC response is greatest in the cvHCV > cirrhosis > stable cases. DR may play a role in aggressive HCV recurrence post-LT. The cvHCV rarely occurs in donors <30 yrs.