This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage > or =F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient > or=6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients (P<0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49-0.91; P=0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54-0.94; P=0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67-0.98; P=0.005), and HA (AUC: 0.80; CI 95%: 0.55-0.94; P=0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.