02). In contrast, a smaller study from a different group—performed on 129 patients with HCV genotype 1—failed to find a similar association.21 Thompson et al. exploited the large patient population enrolled in the IDEAL study to investigate the relationship between IL28B polymorphisms and PKC inhibitor liver disease severity.22, 23 In the first analysis, 1,329 patients were genotyped and the researchers observed no relationship between IL28B rs12979860 and advanced

fibrosis (METAVIR stage F3-F4). In the second analysis, however, the researchers did see a link between rs12979860 genotype, alanine aminotransferase (ALT) levels, and necroinflammatory activity, with C/C patients find more having higher pretreatment ALT values and more often moderate-to-severe (METAVIR stage A2-A3) necroinflammatory activity. Because elevated ALT and high histological grading are known to be associated with a faster fibrosis progression in patients with chronic hepatitis C, in principle, these findings could support a role of the IL28B polymorphisms as a determinant of disease severity.24 However, a limitation of all these studies is represented by the fact that the association between IL28B genetic

variants and the presence of advanced fibrosis or cirrhosis was investigated without taking into consideration the time elapsed from the acquisition of the infection. For this reason, we decided to assess the potential association between IL28B polymorphisms and the rate of progression of liver fibrosis in a cohort of well-characterized Dipeptidyl peptidase patients for whom an accurate estimation of the date of infection could be obtained. Additionally, in the attempt to minimize the role of confounding factors in the interpretation of our data, we restricted our analysis to Caucasian patients only and excluded also patients with diabetes or those reporting past or current regular alcohol consumption. Using such strict inclusion criteria, we found that the host genetic background at the IL28B locus is not associated with the risk of developing

advanced fibrosis. Conversely, we show that other factors have a strong impact on disease outcome, being strongly associated with fibrosis progression, as previously reported.1, 2 In a first effort to correlate disease progression with host and external variables, we modeled the fibrosis progression rate as a continuous outcome, considering the ratio between fibrosis level and disease duration. Although this approach might have been biased by the assumption that the rate of progression to cirrhosis remains constant over time,15 this method represents a way to consider the duration of the chronic disease within the model, instead of a simple split of the population in two groups on the basis of fibrosis score alone.