Molecular and Contextual Markers of Hepatitis C Virus and Drug Abuse

Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease. To describe the HCV-infected population in the United States. Nationally representative household survey. U.S. civilian, noninstitutionalized population. 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002. All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured. The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV-positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV-positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA-positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA-positive participants between 20 and 59 years of age. Incarcerated and homeless persons were not included in the survey. Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.

Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection.