Underascertainment of Acute HCV Infections Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System A Case Series and Chart Review

At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100 000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and hepatitis B infections, which are diagnosed with immunoglobulin M (IgM) antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCVs), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17 000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugs—the group with highest incidence of infection—often do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to its department of public health. Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics.