Serum pro-collagen III peptide levels are related to lobular necrosis in untreated patients with chronic hepatitis C

Objective: Liver biopsy is mandatory for correctly grading and staging chronic hepatitis activity. Nevertheless, serum markers of fibrogenesis may be useful to help us understand the mechanisms of the fibrogenic process, to follow-up patients, and to establish the efficacy of therapy. In this study, our aim was to identify the relationships between pro-collagen III peptide (PIIIP) serum levels and detailed liver histology in a group of untreated patients with chronic hepatitis C (CHC). Methods: We studied 147 CHC patients. Correlation analysis of PIIIP serum levels was performed in 109 patients, after having excluded those with alcohol abuse or concomitant hepatitis B virus infection. PIIIP serum levels were assessed using an assay that measures both Col 1-3 peptide (reflecting collagen synthesis) and Col 1 peptide (reflecting collagen degradation). Relationships of serum PIIIP with histology was carried out by evaluating grading and staging separately. Moreover, each component of the necro-inflammatory score was also taken into consideration. Results: PIIIP levels were abnormal in 101 patients (93%). Moreover, PIIIP levels were no different between patients with (12.1 ± 6.3 ng/ml) or without (13 ± 5.8 ng/ml) fibrosis. In univariate analysis, no relationship was observed with fibrosis (r_s = 0.033, not significant), while PIIIP levels were significantly correlated with lobular necrosis only (r_s = 0.295, P = 0.0020). Multivariate analysis confirmed this latter finding (P = 0.0150). Among biochemical parameters, PIIIP showed relationships with aminotransferase (AST, r_s = 0.294, P = 0.0022; ALT, r_s = 0.236, P = 0.0142) and alkaline phosphatase (r_s = 0.146, P = 0.0223). Conclusions: In patients with CHC, serum PIIIP levels reflect histological parameters strictly related to fibrogenesis. Therefore, PIIIP is a useful tool to evaluate ongoing fibrogenic activity of CHC. A complete histological score is needed in order to understand the relationships between biochemical markers of fibrogenesis and histology.