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Original Research |

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

Shauna Onofrey, MPH; Jasneet Aneja, MPH; Gillian A. Haney, MPH; Ellen H. Nagami, MPH; Alfred DeMaria Jr., MD; Georg M. Lauer, MD, PhD; Kelsey Hills-Evans, MD; Kerri Barton, MPH; Stephanie Kulaga, BA; Melinda J. Bowen, RN; Noelle Cocoros, DSc, MPH; Barbara H. McGovern, MD; Daniel R. Church, MPH; and Arthur Y. Kim, MD
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 30 June 2015.


From Massachusetts Department of Public Health, Jamaica Plain; Massachusetts General Hospital, Harvard Center for AIDS Research, Boston University School of Public Health, Harvard Medical School, Harvard Pilgrim Health Care Institute, and Tufts Medical School, Boston; University of Massachusetts Correctional Healthcare, Worcester; and Seres Health, Cambridge, Massachusetts.

Disclaimer: Views expressed in this article are solely those of the authors and do not represent and should not be construed to representation a determination of policy of the State of Massachusetts.

Grant Support: Dr. Kim is supported by the National Institutes of Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases (grants U19 AI066345, U19 AI082630, R01 DA033541, and R01 DA031056). Dr. Lauer is supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (grants U19 AI066345, U19 AI082630, and R01 AI105035). The MDPH was also supported by the Centers for Disease Control and Prevention (grant CDC-RFA-PS13-130302CONT14).

Disclosures: Dr. McGovern reports personal fees from AbbVie Pharmaceuticals outside the submitted work. Mr. Church reports grants from the Centers for Disease Control and Prevention during the conduct of the study. Dr. Kim reports grants from the National Institutes of Health, personal fees from Bristol-Myers Squibb, and grants and personal fees from AbbVie Pharmaceuticals and Gilead Sciences during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2939.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol: Available from Dr. Kim (e-mail, akim1@mgh.harvard.edu). Statistical code and data set: Available from Ms. Onofrey (e-mail, shauna.onofrey@state.ma.us).

Requests for Single Reprints: Arthur Y. Kim, MD, Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Cox 5, Boston, MA 02114; e-mail, akim1@mgh.harvard.edu.

Current Author Addresses: Ms. Onofrey, Ms. Haney, and Mr. Church: Massachusetts Department of Public Health, 305 South Street, Room 516A, Jamaica Plain, MA 02130.

Ms. Aneja: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.

Ms. Nagami: Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111.

Dr. DeMaria: Medical Director, State Epidemiologist, Bureau of Infectious Disease, Massachusetts Department of Public Health, William A. Hinton State Laboratory Institute, 305 South Street, Jamaica Plain, MA 02130.

Dr. Lauer: Gastrointestinal Unit, Massachusetts General Hospital, Warren 1019A, 55 Fruit Street, Boston, MA 02114.

Dr. Hills-Evans: Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.

Ms. Barton: Massachusetts Department of Public Health, 305 South Street, Room 511, Jamaica Plain, MA 02130.

Ms. Kulaga: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.

Ms. Bowen: Massachusetts Partnership for Correctional Health Care, 10 Turnpike Road, Suite 308, Westborough, MA 01581.

Ms. Cocoros: Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, Boston, MA 02215.

Dr. McGovern: Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111.

Dr. Kim: Massachusetts General Hospital, 55 Fruit Street, Cox 5, Boston, MA 02114.

Author Contributions: Conception and design: S. Onofrey, J. Aneja, E.H. Nagami, A. DeMaria, G.M. Lauer, B.H. McGovern, D.R. Church, A.Y. Kim.

Analysis and interpretation of the data: S. Onofrey, J. Aneja, G.A. Haney, E.H. Nagami, A. DeMaria, K. Hills-Evans, K. Barton, N. Cocoros, B.H. McGovern, D.R. Church, A.Y. Kim.

Drafting of the article: S. Onofrey, J. Aneja, G.A. Haney, E.H. Nagami, A. DeMaria, K. Barton, N. Cocoros, B.H. McGovern, D.R. Church, A.Y. Kim.

Critical revision of the article for important intellectual content: S. Onofrey, A. DeMaria, N. Cocoros, B.H. McGovern, D.R. Church, A.Y. Kim.

Final approval of the article: S. Onofrey, E.H. Nagami, A. DeMaria, G.M. Lauer, K. Hills-Evans, K. Barton, S. Kulaga, N. Cocoros, B.H. McGovern, A.Y. Kim.

Provision of study materials or patients: A.Y. Kim.

Statistical expertise: S. Onofrey, J. Aneja, A.Y. Kim.

Obtaining of funding: G.M. Lauer, A.Y. Kim.

Administrative, technical, or logistic support: J. Aneja, A. DeMaria, S. Kulaga.

Collection and assembly of data: S. Onofrey, J. Aneja, G.A. Haney, K. Hills-Evans, K. Barton, S. Kulaga, M.J. Bowen, A.Y. Kim.


Ann Intern Med. 2015;163(4):254-261. doi:10.7326/M14-2939
Text Size: A A A

Background: In 2010, the incidence of hepatitis C virus (HCV) infection in the United States was estimated to be 17 000 cases annually, based on 850 acute HCV cases reported to the Centers for Disease Control and Prevention by local public health authorities. Absence of symptomatic disease and lack of a specific laboratory test for acute infection complicates diagnosis and surveillance.

Objective: To validate estimates of the incidence of acute HCV infection by determining the reporting rate of clinical diagnoses of acute infection to the Massachusetts Department of Public Health (MDPH) and Centers for Disease Control and Prevention.

Design: Case series and chart review.

Setting: Two hospitals and the state correctional health care system in Massachusetts.

Patients: 183 patients clinically diagnosed with acute HCV infection from 2001 to 2011 and participating in a research study.

Measurements: Rate of electronic case reporting of acute HCV infection to the MDPH and rate of subsequent confirmation according to national case definitions.

Results: 149 of 183 (81.4%) clinical cases of acute HCV infection were reported to the MDPH for surveillance classification. The MDPH investigated 43 of these reports as potential acute cases of HCV infection based on their surveillance requirements; ultimately, only 1 met the national case definition and was counted in nationwide statistics published by the Centers for Disease Control and Prevention. Discordance in clinical and surveillance classification was often related to missing clinical or laboratory data at the MDPH as well as restrictive definitions, including requirements for negative hepatitis A and B laboratory results.

Limitation: Findings may not apply to other jurisdictions because of differences in resources for surveillance.

Conclusion: Clinical diagnoses of acute HCV infection were grossly underascertained by formal surveillance reporting. Incomplete clinician reporting, problematic case definitions, limitations of diagnostic testing, and imperfect data capture remain major limitations to accurate case ascertainment despite automated electronic laboratory reporting. These findings may have implications for national estimates of the incidence of HCV infection.

Primary Funding Source: National Institutes of Health.

Figures

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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.

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Figure 2.

Study flow diagram.

Bottlenecks in acute HCV case classification are indicated. Cases that were never reported were ineligible for further investigation. Further investigation was impaired by lack of completed case report forms, lack of complete ALT data, and restrictive surveillance definitions. CDC = Centers for Disease Control and Prevention; CRF = case report form; HCV = hepatitis C virus; MAVEN = Massachusetts Virtual Epidemiologic Network.

* Because they lacked signal–cutoff ratios, recombinant immunoblot assays, or positive HCV RNA or genotypes.

† Because they were older than 25 y, had no jaundice, and had alanine aminotransferase levels <400 U/L.

‡ Because they lacked complete hepatitis A or B virus data and acute illness, and alanine aminotransferase levels in MAVEN were <400 U/L.

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Appendix Figure.

Proportion of acute HCV clinical cases reported to the MDPH from BAHSTION, by year.

Enhanced laboratory reporting from Massachusetts General Hospital since October 2008 and Lemuel Shattuck Hospital since 2010. BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; MDPH = Massachusetts Department of Public Health.

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Figure 3.

Comparison of peak ALT level documented in BAHSTION, closest level to time case reported, and earliest/highest levels in MAVEN.

ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; MAVEN = Massachusetts Virtual Epidemiologic Network.

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