Author/Authors :
Zaher, Ebtsam R Radiation Sciences Department - Medical Research Institute - Alexandria University, Alexandria, Egypt , Ghazal, Abeer A Microbiology Department - Medical Research Institute - Alexandria University, Alexandria, Egypt , Ellabban, Wael A Clinical Pathology Department - Medical Research Institute - Alexandria University, Alexandria, Egypt , El-Deeb, Mona Clinical Pathology Department - Medical Research Institute - Alexandria University, Alexandria, Egypt , Al-Ghaleed, Lamyaa Internal Medicine Department - Medical Research Institute - Alexandria University, Alexandria, Egypt
Abstract :
Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring
hepatitis C-infected patients for hepatocellular carcinoma development is an important
clinical issue to diagnose these patients during the potentially curable early-stage of disease.
This study aims to evaluate the role of N-terminal procollagen III, matrix metalloproteinase-
2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver
function tests as predictors of hepatocellular carcinoma development upon long-term followup
of non-responding hepatitis C virus patients.
Methods: The study included 850 treatment-naïve hepatitis C virus genotype 4a adult
patients; after treatment, 360 achieved sustained viral response while 490 did not. Nonresponding
patients had a 5-year rate for hepatocarcinogenesis of 8.4% and a 10-year rate
of 27.5%. N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix
metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests were evaluated
in all patients before and after treatment, and after hepatocellular carcinoma development.
The study also included a group of 50 hepatocellular carcinoma patients who were negative
for hepatitis C and hepatitis B viruses, and a group of 50 healthy subjects as controls.
Results: The non-responders had significantly higher age, stage, grade, viral load, alanine
aminotransferase, and aspartate aminotransferase than responders. Also N-terminal procollagen
III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, and alphafetoprotein
were significantly higher in non-responders; after treatment they decreased in
responders. In non-responders they remained higher than the control. The most significant
risk factors for hepatocellular carcinoma development in non-responding hepatitis C virus
patients were male gender and increased age, stage, grade, aspartate aminotransferase, Nterminal
procollagen III, and tissue inhibitor of matrix metalloproteinase-1. Patients with
viral-hepatocellular carcinoma were of significantly lower age, higher grade, stage, γ-glutamyltransferase,
N-terminal procollagen III, and matrix metalloproteinase-2 than non-viral
hepatocellular carcinoma patients. Percent positive N-terminal procollagen III, tissue inhibitor
of matrix metalloproteinase-1, and alpha-fetoprotein were significantly higher in viral
hepatocellular carcinoma patients.
Conclusion: Data suggest that high N-terminal procollagen III and tissue inhibitor of matrix
metalloproteinase-1levels after treatment might be particularly important as markers of
hepatitis C virus-non-responding patients who are at higher risk of developing hepatocellular
carcinoma, especially in older males with high stage and grade liver disease. However,
studies of larger scale are needed to verify this suggestion.
Keywords :
Predictive marker , AFP , TIMP-1 , MMP-2 , PIIINP , Hepatocellular carcinoma (HCC) , HCV
