BackgroundHepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.MethodsWe studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].ResultsAlready established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.ConclusionsThe fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.

Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

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