It is currently estimated that 3 to 4 million individuals in the United States and up to 170 million individuals worldwide are chronically infected with hepatitis C virus (HCV).1–3 HCV remains the most common chronic blood-borne infection in the United States and accounts for up to two-thirds of newly diagnosed cases of chronic liver disease.3, 4 Because HCV is primarily transmitted through parenteral routes, populations known to have a particularly increased risk of exposure to HCV include recipients of blood transfusions before 1992 or coagulation factors before 1987, hemophiliacs, hemodialysis patients, individuals infected with human immunodeficiency virus (HIV), and injection drug users.5 Consequently, these groups are included in the current recommendations for identifying individuals who would benefit from screening5, 6 (Table 1). Although these recommendations have been in place for more than a decade, it remains questionable whether this strategy has been effective in identifying individuals with chronic HCV infections, most of whom were born between 1945 and 1964.3 An additional consideration is that certain populations with the greatest prevalence of HCV, such as injection drug users, incarcerated individuals, and the homeless, may not have access to health care or may not be included in population-based surveillance programs; as a result, the true prevalence of HCV may be underestimated.1 Injection drug use remains the most frequent means of HCV transmission in the United States; the seroprevalence of the antibody to HCV may rise to more than 70% with 3 to 5 years of habitual exposure7, 8 (Fig. 1). Efforts to implement prevention and treatment strategies in this population may become increasingly important for controlling new HCV infections.
|Injection drug users or individuals with a history of injection drug use|
|Individuals infected with HIV|
|Individuals with hemophilia|
|Recipients of clotting factors or other blood products before 1987|
|Individuals with elevated liver enzyme levels|
|Recipients of solid organ transplants before 1992|
|Recipients of blood transfusions before 1992|
|Children born to HCV- positive mothers|
|Individuals with any known potential exposure via HCV-positive blood donors, organ donors, or occupational exposures|
|Sexual partners of HCV-infected individuals|
The importance of effective screening strategies is highlighted by the recent availability of increasingly effective antiviral therapy.9, 10 The achievement of long-term viral clearance after a course of antiviral therapy, which is defined as a sustained virological response, is durable and demonstrates that the eradication of HCV is possible with successful treatment.11, 12 In addition, the successful treatment of an HCV infection can have a major impact on the natural history of HCV-associated chronic liver disease because the achievement of a sustained virological response may result in a substantial decrease in the risk of hepatocellular carcinoma (HCC) and liver-related mortality.13–17 Although an important step in minimizing the overall burden associated with HCV infections is the identification of individuals with chronic HCV who may be candidates for antiviral therapy, emerging data suggest that the majority of individuals with chronic HCV have not been diagnosed and remain untreated (Fig. 2). As many as 75% of those with chronic HCV in the United States are unaware that they are infected.18 In addition, only a small proportion of those diagnosed with chronic HCV undergo antiviral therapy.19–22 Barriers to treatment may include a failure to identify the infection, a lack of awareness of the seriousness of the infection, limited access to adequate health care or insurance, a fear of treatment side effects, and misperceptions about the effectiveness of treatment.23 Outlining a national strategy for the prevention and control of HCV, a recent report by the Institute of Medicine emphasized these findings and stressed the importance of increased awareness, recognition, and management of chronic HCV.18
Up to 85% of adults acutely exposed to HCV progress to a chronic infection; at least 20% of these individuals may progress to advanced liver disease over a 20- to 30-year period.24 Factors associated with an increased risk of disease progression include the duration of the HCV infection, heavy alcohol intake, advanced age, obesity, fatty liver disease, male sex, and HIV coinfection with low CD4 cell counts.25 Chronic liver disease associated with HCV is a major health care burden in the United States and globally and results in significant morbidity and mortality. Currently, more than 12,000 deaths occur annually in the United States as a result of HCV-related liver disease,26 and the number of deaths attributable to HCV may be greater than 360,000 per year on a global scale.27 As individuals with HCV continue to age and their duration of chronic infection increases, the prevalence of advanced hepatic fibrosis, end-stage liver disease, and HCC is also increasing. Indeed, the prevalence of cirrhosis and decompensation has doubled over the last decade, and the prevalence of HCC has increased 20-fold.28 Although HCV remains the leading indication for liver transplantation in the United States, the proportion of cases attributable to HCV appears to have plateaued, perhaps because of the aging of these individuals. However, the proportion of transplants related to HCC is rapidly increasing, and most of these cases are due to HCV29–31 (Fig. 3).
It has been projected that the overall prevalence of HCV in the United States will decline over the next 2 decades; however, the health care and social burden associated with advancing HCV-related liver disease will continue to rise.33, 34 Predictive modeling has estimated that by 2030, the proportion of individuals with chronic HCV who have cirrhosis will approach 50% (Fig. 4). Likewise, the prevalence of clinical decompensation and HCV-associated HCC is expected to increase during this time period. In addition, the annual number of liver-related deaths attributed to chronic HCV could more than double in the years leading up to 2030.33 Ultimately, this trend will have an economic impact as well. The estimated economic burden of HCV in the United States in 1997 was $5.5 billion.35 This amount is expected to nearly double to just under $10 billion per year over the next decade.36
Antiviral therapy should decrease the prevalence of cirrhosis and liver-related deaths associated with HCV. The impact of therapy should become more pronounced as the efficacy of treatment improves. The treatment of half of HCV-infected persons today could result in overall decreases of 30% to 40% in liver failure, HCC, and liver-related mortality over the next decade.33 These findings highlight the importance of the early detection and selection of treatment candidates. An improved understanding of the demographics of HCV infection may lead to more effective screening strategies, which could possibly include both a targeted approach and the casting of a wider net based on age groups at the greatest risk for past exposure.37 Ultimately, the control of new HCV infections will require continued efforts to educate and increase awareness in populations at the greatest risk, including those exposed to injection drug use.