Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.
BACKGROUND
This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C.


METHODS
The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis.


RESULTS
HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05).


CONCLUSIONS
This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.
Tsamandas
Athanassios C
AC
Department of Pathology, School of Medicine, University of Patras, Patras, Greece. tsamanda@otenet.gr
Syrokosta
Ioulia
I
Thomopoulos
Konstantinos
K
Zolota
Vassiliki
V
Dimitropoulou
Dimitra
D
Liava
Anna
A
Coupoulou
Anna Antona
AA
Siagris
Dimitrios
D
Petsas
Theodore
T
Karatza
Chrisoula
C
Gogos
Charalambos A
CA
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D053539:Keratin-19 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D000509:alpha-Fetoproteins / Q000032:analysis
D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053539:Keratin-19; D053552:Keratin-7; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b