Patients order inhibitor for whom the date of infection was unknown were excluded as well. The stored DNA samples from the 168 recruited patients were analyzed for the three mutations that are responsible for hypercoagulable states, that is, FV Leiden, PT20210 and MTHFR. This study was approved by the local Helsinki ethics committees. Definitions of slow and fast fibrosis Fibrosis rates were calculated by dividing the fibrosis stage by the number of years of infection. We employed Poynard��s fibrosis progression model in order to define our patients�� fibrosis rate status and classified them as ��fast fibrosers�� or ��slow fibrosers��[12].

According to the model, the means of the fibrosis progression rates, as predicted by age and infection duration, are as follows: (1) patients who were infected at an age of less than 20 years were expected to develop cirrhosis after 40 years of infection; (2) patients who were infected in their third or fourth decade progress to cirrhosis after 35 years of infection; (3) patients in the fifth decade of life were expected to develop cirrhosis after 20 years of infection; and (4) patients who were older than 50 years were expected to become cirrhotic after 15 years of infection. Histopathology Liver biopsy examinations were performed at each center and analyzed by the local pathologist, wherein the fibrosis stage and activity grading were evaluated according to the METAVIR scoring system. Fibrosis was staged on a scale of 0-4: F0, no fibrosis; F1, portal fibrosis without septa; F2, few septa; F3, numerous septa without cirrhosis; and F4, cirrhosis.

The grading of activity that was assessed by the METAVIR system (based on the intensity of necroinflammatory Dacomitinib activity, largely on necrosis) was scored as follows: A0, no histological activity; A1, mild activity; A2, moderate activity and A3, severe activity. In order to assess liver biopsy quality, Regev quality criteria were used (fragment length of 15 mm or more, five or more portal tracts and one fragment). A biopsy that is between 10 and 15 mm in length and has less than five portal tracts or is fragmented is considered to be a fair quality biopsy, whereas a biopsy is considered to be of poor quality when it is less than 10 mm in length. DNA collection and gene analysis DNA samples were isolated from the peripheral blood of all patients. DNA extraction was performed using the QIAamp DNA blood kits and silica-membrane-based DNA purification (Qiagen, Germany).