Daniel R. Church

Emerging Epidemic of Hepatitis C Virus Infections Among Young Nonurban Persons Who Inject Drugs in the United States, 2006–2012

BACKGROUND Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). METHODS We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. RESULTS From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. CONCLUSIONS These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.

An Epidemiologic Update on Hepatitis C Infection in Persons Living With or at Risk of HIV Infection

Due to shared routes of transmission, coinfection with both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) is relatively common and results in accelerated liver disease, driving morbidity and mortality. Deaths related to HCV now exceed deaths related to HIV in the United States, and co-infected patients bear a significant proportion of that mortality. This burden may be addressed by novel antiviral therapies that promise increased rates of cure or by enhanced access to liver transplantation, but these are costly interventions. Ultimately, the future burden of coinfection is addressed by greater understanding of who is at risk for development of each infection, thus guiding preventive efforts. Key recent reports regarding the US burden of morbidity and mortality due to HCV and groups at risk for coinfection are reviewed, with a focus on recently described HCV occurring among young injection drug users and men who have sex with men. Given the lack of available vaccine against HCV, enhanced detection and surveillance is a vital component of our public health strategy to combat HCV.

Automated Identification of Acute Hepatitis B Using Electronic Medical Record Data to Facilitate Public Health Surveillance

Background Automatic identification of notifiable diseases from electronic medical records can potentially improve the timeliness and completeness of public health surveillance. We describe the development and implementation of an algorithm for prospective surveillance of patients with acute hepatitis B using electronic medical record data. Methods Initial algorithms were created by adapting Centers for Disease Control and Prevention diagnostic criteria for acute hepatitis B into electronic terms. The algorithms were tested by applying them to ambulatory electronic medical record data spanning 1990 to May 2006. A physician reviewer classified each case identified as acute or chronic infection. Additional criteria were added to algorithms in serial fashion to improve accuracy. The best algorithm was validated by applying it to prospective electronic medical record data from June 2006 through April 2008. Completeness of case capture was assessed by comparison with state health department records. Findings A final algorithm including a positive hepatitis B specific test, elevated transaminases and bilirubin, absence of prior positive hepatitis B tests, and absence of an ICD9 code for chronic hepatitis B identified 112/113 patients with acute hepatitis B (sensitivity 97.4%, 95% confidence interval 94–100%; specificity 93.8%, 95% confidence interval 87–100%). Application of this algorithm to prospective electronic medical record data identified 8 cases without false positives. These included 4 patients that had not been reported to the health department. There were no known cases of acute hepatitis B missed by the algorithm. Conclusions An algorithm using codified electronic medical record data can reliably detect acute hepatitis B. The completeness of public health surveillance may be improved by automatically identifying notifiable diseases from electronic medical record data.

Enhancing Surveillance for Hepatitis C through Public Health Informatics

Disease surveillance for hepatitis C in the United States is limited by the occult nature of many of these infections, the large volume of cases, and limited public health resources. Through a series of discrete processes, the Massachusetts Department of Public Health modified its surveillance system in an attempt to improve timeliness and completeness of reporting and case follow-up of hepatitis C. These processes included clinician-based reporting, electronic laboratory reporting, deployment of a Web-based disease surveillance system, automated triage of pertinent data, and automated character recognition software for case-report processing. These changes have resulted in an increase in the timeliness of reporting.

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.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. 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 100000 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 B infections, which are diagnosed with 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-HCV), 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 17000 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 drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). 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. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora

Screening for Hepatitis C as a Prevention Enhancement (SHAPE) for HIV: An Integration Pilot Initiative in a Massachusetts County Correctional Facility

Objectives. The Massachusetts Department of Public Health (MDPH) and the Barnstable County Sheriffs Department (BCSD) in Massachusetts initiated a pilot program in July 2009 offering education and hepatitis C virus (HCV) antibody testing to inmates and detainees, concurrent with routine HIV testing. The initiative was implemented to assess the feasibility of integrating HCV screening into an HIV screening program in a correctional setting and the efficacy of linking HCV antibody-positive inmates to clinical care upon release. Methods. Through the Screening for Hepatitis C as a Prevention Enhancement initiative, HCV and HIV testing were offered to inmates and detainees shortly after admission, and by request at any time during incarceration. In preparation for release, referrals were made to community-based medical providers for HCV follow-up care. Data from BCSD were compared with routine surveillance data received by MDPH. Confirmatory HCV test results received by April 15, 2012, were considered indicators of appropriate post-release clinical care. Results. From July 2009 through December 2011, 22% (n=596) and 25% (n=667) of 2,716 inmates/detainees accepted HCV and HIV testing, respectively. Of those tested for HCV antibody, 20.5% (n=122) were positive. Of those tested for HIV antibody, 0.8% (n=5) were positive. Of the inmates who tested HCV positive at BCSD and had been released, 37.8% were identified as receiving post-release medical care. Conclusions. We determined that integration of HCV education and screening into correctional facilities is feasible and reveals high rates of HCV infection. Although this model presupposes programmatic infrastructure, elements of the service design and integration could inform a range of correctional programs. Effective linkage to care, while substantial, was not routine based on our analysis, and may require additional resources given its cost and complexity.

Hepatitis B Virus Infection and Immunizations among Asian American College Students: Infection, Exposure, and Immunity Rates.

Abstract Objectives: To evaluate the prevalence of hepatitis B virus (HBV) infection, exposure, and immunity among Asian American college students as a basis for evaluating HBV screening and vaccination policy. Participants and Methods: Self-identified Asian American college students aged 18 years or older were examined. Serological tests of HBV surface antigens, antibodies to HBV core antigens (anti-HBc), and antibodies to HBV surface antigens (anti-HBs) were used to determine HBV infection and immunization prevalence. Results: Among US-born students (n = 66), none was infected with HBV, 68% (n = 45) had immunity from vaccination, and 1 student had evidence of past exposure to HBV. Among foreign-born students (n = 142), 4% (n = 5) had evidence of chronic HBV infection, 62% (n = 88) had immunity from vaccination, and 19% (n = 27) had results indicating past exposure to HBV. Asian American college students showed very little knowledge of HBV vaccination; 43% reported that they had received vaccination, whereas 50% did not know whether they had received it or not. Conclusions: The prevalence of current and past HBV infection among foreign-born Asian American college students is significantly higher (p < .01), than US-born students. The lack of awareness of their HBV-infected status points out the importance of routine HBV screening of high-risk populations such as Asian students.

Debunking the myth: low knowledge levels of HBV infection among Asian American college students

Objective: To examine the hepatitis B virus (HBV)-related knowledge among Asian American college students and to determine whether there are significant differences in the level of HBV knowledge among Asian American subgroups. Methods: A cross-sectional survey was self-administered to assess a sample of 258 Asian American students′ knowledge about HBV at the campus of the research site. Results: Knowledge regarding transmission and consequences of HBV infection was poor. Of a possible knowledge score of 14, the median number of correct answers was eight. There were no significant differences between the subgroups of Asian American college students in total knowledge of HBV infection. Conclusion: The findings of this study point to the fact that the lack of knowledge and awareness is not limited to community settings only but also includes higher education environment. This finding brings to the forefront the importance of HBV education for Asian American college students.

Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance SystemA Case Series and Chart ReviewUnderascertainment of Acute HCV Infections

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.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. 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 100000 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 B infections, which are diagnosed with 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-HCV), 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 17000 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 drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). 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. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora

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.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. 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 100000 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 B infections, which are diagnosed with 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-HCV), 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 17000 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 drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). 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. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora