Clinical Guidelines for the Medical Management of Hepatitis C

B. Epidemiology and Natural History

It is estimated that 170 million people worldwide are chronically infected with HCV, known as non-A, non-B hepatitis prior to 1989.3 HCV is the most common chronic blood-borne infection in the U.S.4 The Third National Health and Nutrition Examination Survey (NHANES III) showed that the prevalence of antibody to HCV (anti-HCV) in the U.S. is 1.8% or approximately 4 million people.5 Seventy-four percent of these (i.e., an estimated 2.7 million people) are also positive for HCV RNA, and considered chronically infected.6

The incidence of HCV infection in the U.S. began rising in the 1960's, peaked in the late 1980's, and began declining in the 1990's. In 2001, the annual infection rate was 25,000 new cases per year.7 However, the occurrence of symptomatic CHC among people initially infected in the 1970's and 1980's could increase significantly over the next 10 years, peaking around 2015.4 For example, the age-adjusted death rate for "non-A, non-B" viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately in the U.S., there were 3,759 deaths attributed to HCV, although this is likely an underestimate. In 1998, an estimated 140,000 hospital discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the U.S. There was a five-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000 and, currently, more than one third of liver transplant candidates have HCV.1

The incidence of new cases of HCV infection in the U.S. is declining. However, the disease burden of HCV infection is projected to continue to rise in the U.S. in the foreseeable future with a four-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (i.e., those with infection for 20 years or longer).1,8 In a detailed analysis, Leigh et al. estimated that the costs of HCV in the U.S. in 1997 were $5.46 billion. Of this amount, direct costs, defined as inpatient and outpatient medical care and administrative expenses, accounted for $1.8 billion (33%). Indirect costs, defined as lost wages, benefits and productivity, accounted for the remainder.8

The prevalence of HCV infection in the U.S. is higher among African-Americans (3.2%) and Hispanics (2.1%) than among non-Hispanic Caucasians (1.5%). In the general population, males have higher prevalence rates than females (2.5% and 1.2%, respectively); however, in incarcerated populations the reverse has been seen. The strongest factors independently associated with HCV infection are injection drug use (IDU) and, to a lesser extent, high-risk sexual behavior. Higher prevalence rates have been observed in people who are divorced or separated, people living in poverty, people who have had 12 years or less of education, people receiving hemodialysis, and people who have had a solid organ transplantation. In addition, higher prevalence rates may be seen following HSV-2 infection or blood transfusion, and with perinatal exposure.3,6,9

The seroprevalence of antibodies to HCV is approximately 0.2% in children less than 12 years of age and 0.4% in those 12 to 19 years of age. In several studies, viremia occurs in 50-75% of antibody-positive children. Spontaneous HCV clearance appears to occur more commonly in children, particularly during the first year after infection.10

Certain subpopulations in the U.S. have HCV infection prevalence rates higher than that seen in the general population. These include inmates entering correctional facilities (in New York State, 13.3% in males and 24% in females; 23.1% in Rhode Island; 29.7% in Maryland; and, in Texas, 29.7% among males, and 48.6% among females), and homeless men (50%).9,11-14 In the U.S. and other western countries, and in Japan, most HCV-infected people have genotypes 1, 2 or 3. In the U.S., 73.7% of chronically infected individuals have genotype 1. Elsewhere in the world, other genotypes are prevalent, and may even predominate: genotype 4 in Africa and the Middle East; genotype 5 in South Africa; genotypes 6 to 9 in southern China and Southeast Asia; and genotypes 10 and 11 in Indonesia.6,15

Acute HCV infection is often asymptomatic or presents with non-specific symptoms. Jaundice occurs in only about 25% of cases. As a result, acute infection is not easily recognized and few patients come to medical attention. Spontaneous resolution occurs in up to 25% of patients; hence, the majority of patients become chronically infected with persistent viremia.3

Once chronic infection is established, it is unlikely that spontaneous clearing will occur.16 Spontaneous clearance of acute HCV infection occurs more frequently with genotype 3 compared to genotype 1, with clearance rates of 37% and 7%, respectively.17 Spontaneous resolution occurs less frequently with co-infection with human immunodeficiency virus (HIV), and with excessive alcohol use.18

Co-infection with HIV and hepatitis is common, especially in areas with high proportions of IDU. Nationally, approximately 30% of people infected with HIV are estimated to be co-infected with HCV, and 50%-90% of people who acquired HIV through injection drug use (IDU) are co-infected with HCV. Further recommendations for the HIV/HCV co-infected patient are provided at: CRITERIA FOR THE MEDICAL CARE OF ADULTS WITH HIV INFECTION

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