HEPATITIS C: TRANSMISSION RISK, NATURAL HISTORY, AND PREVENTION (by Michael S. Bronze, William M. Tierney, Syed M. Rizvi).

Epidemiology

Hepatitis C virus (HCV) is a significant healthcare problem, affecting more than 170 million people worldwide, or 3-4% of the world’s population. Prevalence of HCV in different geographic regions varies from 0.1-12%, with rates of 1.8% in the United States, 2.5-10% in South America and Africa, and more than 10% in Egypt and Bolivia. Worldwide, as many as 4 million new infections occur annually. In the United States, 65% of those infected with HCV are aged 30-49 years.

Risk factors for transmission include intravenous (ie, injection) and intranasal drug use, contaminated blood products, organ transplantation, long-term hemodialysis, and vertical transmission during pregnancy. Less common modes include nosocomial and sexual transmission. In the United States, most new HCV cases (approximately 36,000 annually, although underestimation is likely) are related primarily to injection drug use, while in less developed countries, contaminated injection therapy is frequently the source of transmission. Although the number of new cases in the United States is declining because of blood product screening, the long latency period from time of infection to clinical recognition portends a substantial clinical impact. By the year 2015, the prevalence of HCV-associated cirrhosis, decompensated liver disease requiring liver transplantation, and hepatocellular carcinoma (HCC) will increase dramatically, making HCV a “silent epidemic.” HCV already accounts for approximately 8,000-10,000 deaths annually in the United States.

Of additional concern is the impact of HIV co-infection on the natural history of HCV infection, its transmission, and its response to treatment strategies. In the United States, an estimated 16% of patients with HCV are co-infected with HIV and nearly one third of HIV-positive individuals are also HCV positive. Most of those dually infected acquired HCV by injection drug use, although unprotected sexual activity between homosexual males is also a risk factor.

All known HCV isolates have been divided into 6 phylogenetically distinct groups known as clades, and more than 70 subtypes based on nucleotide sequences and genetic analysis have been identified. Epidemiologically and clinically, 11 genotypes have been identified (see Table 1). Genotype 1b is the most common genotype globally and is principally transmitted through contaminated blood products. The most common genotypes in the United States include 1a, 1b, and 3a, with 1a most often transmitted through injection drug use and accounting for nearly 70% of all infections. Genotypes 1a, 2a, 2b, and 3a are prevalent in Europe, and genotypes 6-11 are common in Southeast Asia and Indonesia. Typically, the genotype, or clade, does not regularly predict clinical presentation, progression of liver disease, or incidence of HCC, but it does predict response to antiviral therapy. Table 1. Epidemiology of the Major HCV Genotypes

HCV Genotype	Geography	Clinical Significance
1a	United States, Northern Europe	Most common genotype in the United States
1b	Worldwide	Often transmitted by transfusion; may have a more aggressive clinical course than other genotypes and higher incidence of HCC; associated with recurrent hepatitis in patients with liver transplants
2a, 2b	Europe, Japan, North America	With genotype 3, excellent treatment responses
2c	North Italy
3a	India, Europe, United States	Associated with intravenous drug use; often associated with hepatic steatosis
6-11	Southeast Asia

Data adapted from Hnatyszyn HJ; Antiviral Therapy 2005;10:1-11.

Transmission

Risk factors associated with HCV infection include injection drug use (or intranasal if using a blood-contaminated device), receipt of blood products (prior to 1990 in the United States), long-term hemodialysis, organ transplantation, receipt of a tattoo from an unsanitary facility, vertical transmission during pregnancy, and sexual or nosocomial exposure. Sexual transmission is relatively inefficient, and the risk of HCV following needle stick injury from contaminated needles ranges from 0-10% (average, 3%). Co-infection with HIV increases the sexual and vertical transmission rates of HCV. Intrafamily transmission is uncommon, and the risk of transmission from an infected patient to a healthcare worker is about 2-5%. Weaker associations include poverty, high-risk sexual behavior, divorce, and fewer than 12 years of formal education. With the advent of blood and blood product screening for all donors in the United States, the risk of acquiring HCV from transfusion is low (see Table 2). Screening all blood donors with antibody testing reduced the risk of acquiring HCV to an estimated 1 in 199,000 as compared to 1 in 144,000 for hepatitis B virus or 1 in 1,048,000 for HIV. Furthermore, the addition of nucleic acid testing to screening likely reduces the risk another 5- to 10-fold. Transmission risk also varies with age and geography. Table 2. Risk of Acquiring Hepatitis C Virus Infection*

Route	Risk of Acquiring
	Hepatitis C	Hepatitis B	HIV
Transfusion of blood product^	1:199,000	1:144,000	1:1,048,000
Needle stick	3%	30%	0.3%

Data derived from Lauer G, Walker BD; N Engl J Med 2001;345:41-52 and Dodd RY; Int J Hematol 2004;80:301-305. *Data apply to US only. ^Data are for all donors to the American Red Cross voluntary blood supply and do not reflect the use of nucleic acid testing (NAT) for detection of HCV or HIV. If NAT is applied, the risk of transfusion-associated HCV is 1:1,390,000 and 1:1,525,000 for HIV.