Although HCV eradication with IFN therapy for CHC has been shown to prevent HCC,[5-9] HCC sometimes develops even after achieving viral eradication.[5] Because the number of sustained virological responders (SVRs) is increasing along with recent advances

in the development of effective anti-HCV therapy, it is very important to determine factors buy PD-0332991 responsible for HCC development among IFN-treated patients. However, this information is difficult to determine because of the paucity of large-scale, long-term cohort studies. The 70-kDa glycoprotein α-fetoprotein (AFP), encoded by a gene located on chromosome 4, is the major serum protein during fetal life.[10] Shortly before birth, AFP is replaced by albumin as the major serum protein,[11,

12] and thereafter, serum AFP levels remain extremely low throughout life (<10 ng/mL). Because serum AFP levels are frequently elevated in patients with HCC and germ-cell tumors, measurement of AFP is widely used as a serological marker for these tumors.[8, 13] However, AFP levels are sometimes elevated in patients with chronic viral Inhibitor Library datasheet hepatitis and cirrhosis who do not have HCC.[3, 19] While one possible explanation for this elevation is liver inflammation, in patients with CHC, the relationship between AFP and markers of liver inflammation such as alanine aminotransferase (ALT) is unclear. Moreover, although several reports suggest that pre-IFN treatment ALT and AFP levels in patients or those in patients who did not undergo subsequent treatment are associated with the development of HCC, it is unclear whether post-IFN treatment ALT and AFP levels are associated with hepatocarcinogenesis in patients with CHC. Hence, to clarify these associations we conducted a large-scale, long-term cohort study of patients

with CHC to analyze the influence of ALT and AFP levels before and after IFN therapy on hepatocarcinogenesis in addition to other host and virological factors. Patients P-type ATPase chronically infected with HCV who had histologically proven chronic hepatitis or cirrhosis and had undergone IFN treatment between 1992 and 2010 were enrolled in the cohort. HCC was definitively ruled out by ultrasonography, dynamic computed tomography (CT), and/or magnetic resonance imaging (MRI) on enrollment. Patients were excluded if they had a history of HCC at the time of liver biopsy, autoimmune hepatitis, primary biliary cirrhosis, excessive alcohol consumption (≥50 g/day), hepatitis B surface antigen, or antihuman immunodeficiency virus antibody. Based on these criteria, a total of 2,689 patients were initially enrolled. Of these, 223 (8.3%) patients were excluded from the cohort because of loss to follow-up. In the remaining 2,466 patients, 133 and 515 patients were excluded from this analysis because of short follow-up and retreatment with IFN-based therapy during the follow-up period, respectively.