Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C

Abstract

The enhanced accumulation of hepatic progenitor cells (HPCs) is related to the risk of progression to hepatocellular carcinoma (HCC). Interferon (IFN) treatment reduces HCC risk in patients with chronic hepatitis C virus (HCV) infection. However, the underlying mechanisms remain unclear. The aim of this study was to examine the effects of IFN treatment on HPC activation in HCV patients. Immunohistochemical detection and computer-assisted quantitative image analyses of cytokeratin 7 (CK7) were performed to evaluate HPC activation in paired pre-and post-treatment liver biopsies from 18 HCV patients with sustained virological response (SVR) to IFN-based therapy and from 23 patients without SVR, as well as normal liver tissues obtained from surgical resection specimens of 10 patients. Pretreatment HCV livers showed increased CK7 immunoreactivity, compared with normal livers (HCV: median, 1.38%; normal: median, 0.69%, P = 0.006). IFN treatment reduced hepatic CK7 immunoreactivity (median, 1.57% pre-IFN vs. 0.69% post-IFN, P = 0.006) in SVR patients, but not in non-SVR patients. The development of HCC following IFN treatment was encountered in 3 non-SVR patients who showed high post-IFN treatment CK7 immunoreactivity (>4%). Successful IFN therapy can reverse enhanced HPC activation in HCV patients, which may contribute to the reduced risk of HCC development in these patients.

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4

“…The current study confirmed previous reports that demonstrated HPCs in HCV-infected liver biopsies in the form of DR as well as IPCs18,33 . More importantly, we found that responders (SVR) had a significantly lower number of HPCs (both DR and IPCs) than non-responders (Non-SVR).…”

“…Another important observation in the present study was that the number of HPCs was significantly higher in later stages of fibrosis. This confirms several previous studies9,10,17,18 and indicates that HPCs participate either directly or indirectly through cross talk with stellate cells in the process of hepatic fibrogenesis. We investigated the relationship between stellate cells and HPCs in chronic HCV in a previous report36.…”

“…Accordingly, we can speculate that in our patients who failed to achieve SVR, HCV protein which resisted response to therapy, was also able to mediate impairment of the cell cycle of mature liver cells and eventually contributes to HPC proliferation. It was interesting to compare our results with those of D'Ambrosio et al33 and Noritake et al18. Both studies estimated the immune expression of HPCs in pre-treatment and post-treatment liver biopsies of chronic HCV to evaluate the effect of interferon therapy on the expression of these cells.…”

“…The authors found that the number of HPCs significantly decreased after SVR. Noritake et al18 proposed that eradication of the virus could improve the HCV-related impairment of mature hepatocyte proliferation with consequent inhibition of HPC replication. Although the aim and design of the afore-mentioned two reports were different from ours, their conclusions are consistent with our findings.…”

“…Hepatic progenitor cells (HPCs) are small cells located in the periportal region of the liver16. Although the role of HPCs in liver fibrogenesis has been extensively studied9,10,17,18, their value in predicting sustained virological response of patients with HCV to treatment was not previously evaluated except in two reports. The first was Tsamandas et al17 on 77 patients with HCV of different genotypes.…”