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We identified correlates of exposure to hepatitis B and C viruses among health department clients in Appalachian Kentucky, a rural region noted for high poverty and low education. Additionally, we investigated risk factors for transmission, and the frequency of use of preventive measures.Patients screened for hepatitis B or C at four county health departments in Appalachian Kentucky were administered a routine prescreening questionnaire and an additional survey designed to obtain detailed personal and behavioral risk factor data. These data were linked to produce a more comprehensive dataset for analysis, including test results, which were attached to the prescreening questionnaire.In total, 92 health department clients participated in the study survey. Of these, test results were available for 80 of the clients. Very few subjects who enrolled in this study tested positive for hepatitis B. Twelve out of 80 participants (15%) tested positive for previous exposure to hepatitis C. No participants reported having human immunodeficiency virus.Transmission of hepatitis C in these rural Appalachian communities is predominantly due to injection drug use. Patients with hepatitis C exposure are similar in their demographic and risk profiles as those seen in urban areas and, despite small numbers, can have a serious impact on small, rural public health systems.