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The American Journal of Managed Care August 2019
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Late Diagnosis of Hepatitis C Virus Infection, 2014-2016: Continuing Missed Intervention Opportunities
Anne C. Moorman, MPH; Jian Xing, PhD; Loralee B. Rupp, MSE; Stuart C. Gordon, MD; Mei Lu, PhD; Philip R. Spradling, MD; Joseph A. Boscarino, PhD; Mark A. Schmidt, PhD; Yihe G. Daida, PhD; and Eyasu H. Teshale, MD; for the CHeCS Investigators
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Late Diagnosis of Hepatitis C Virus Infection, 2014-2016: Continuing Missed Intervention Opportunities

Anne C. Moorman, MPH; Jian Xing, PhD; Loralee B. Rupp, MSE; Stuart C. Gordon, MD; Mei Lu, PhD; Philip R. Spradling, MD; Joseph A. Boscarino, PhD; Mark A. Schmidt, PhD; Yihe G. Daida, PhD; and Eyasu H. Teshale, MD; for the CHeCS Investigators
Late hepatitis C virus infection diagnosis points to a need for earlier screening and treatment before the onset of severe liver disease leading to high cost and diminished outcomes.

More than one-fifth of CHeCS patients with newly diagnosed HCV during 2014-2016—and more than a quarter of those born between 1945 and 1965—had severe liver disease concurrent with initial HCV diagnosis despite many years of care in the health systems, an increase of 5 percentage points since 2006-201115 after the interim initiation of age-based screening recommendations.8 Many patients, particularly those with late diagnosis, had laboratory markers of liver inflammation beginning several years prior to their initial HCV diagnosis, which did not prompt screening and diagnosis with the opportunity for treatment at a likely earlier disease stage.

Although late diagnosis was less common among those born after 1965, a higher proportion of persons with newly diagnosed HCV from 2014 to 2016 were in this age group than in the earlier analysis (37% vs 21%), probably reflecting national increases in HCV transmission and detection among younger age groups, likely related to the opioid epidemic.14,21 Most late diagnoses (82.5%) occurred among persons born in or before 1965, more frequently among men and those with public insurance. The 2012 recommendations for testing of persons born between 1945 and 1965 and increased awareness of HCV have led to more widespread—although still vastly incomplete—testing and identification of infection.7,10-13 However, our data reflect national trends in continued disease progression and increasing morbidity among persons with long-term infection,12,22 including those whose HCV is not yet diagnosed. With the aging of the infected population, the proportion of persons with severe liver disease may continue to increase without greater access to treatment.


This update has many of the same limitations as the earlier analysis.15 Diagnosis codes selected to define late diagnosis were of sufficient severity to correspond with decompensated liver disease rather than mild-to-moderate liver disease. This highly conservative definition of late diagnosis also likely included some patients with advanced HCV infection in the group without late diagnosis. About a quarter of new HCV cases had been previously diagnosed outside the health systems, and patients’ disease status at diagnosis could not be ascertained. It is possible that we missed detection of some outside-system HCV diagnoses, despite lengthy observation time from first health system encounter to first EHR evidence of HCV diagnosis. Our use of a conservative FIB-4 cutoff level for cirrhosis could be anticipated to miss some patients with advanced fibrosis, thus leading to an underestimate. However, the FIB-4 cutoff for cirrhosis of greater than 5.88 was derived and validated specifically in the study cohort and chosen to maximize positive predictive value.20


This study supports the finding that patients with undiagnosed cirrhosis are being followed in health systems for years prior to receiving a diagnosis of HCV, but waiting until it is clear that severe liver disease is present is a failed strategy for reducing morbidity and health costs. Although morbidity and mortality from liver disease and related conditions have been demonstrated to decrease after successful treatment for patients at all stages of disease,23 patients who have already progressed to cirrhosis still remain at risk for hepatocellular carcinoma24 and those with manifestations of ESLD, such as severe portal hypertension, may not experience improvements in those conditions,25 leading to significant economic and health disease burden.3-7 These patients are losing the opportunity to access the healthcare appropriate for those with cirrhosis, such as vaccinations, screening for liver cancer and esophageal varices, and counseling about risks of common medications or foods in those with cirrhosis. Payers should have a role in facilitating recommended testing for HCV infection. Our data highlight the continuing missed opportunities for diagnosis and therapeutic intervention before the onset of severe liver disease, when treatment may involve high costs and diminished outcomes.


The Chronic Hepatitis Cohort Study Investigators include the following investigators and sites: Eyasu H. Teshale, Philip R. Spradling, Anne C. Moorman, Jian Xing, and Yuna Zhong, Division of Viral Hepatitis, National Centers for HIV, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, Georgia; Stuart C. Gordon, David R. Nerenz, Mei Lu, Lois Lamerato, Jia Li, Loralee B. Rupp, Nonna Akkerman, Talan Zhang, Sheri Trudeau, Yueren Zhou, and Kuan-Han Wu, Henry Ford Health System, Detroit, Michigan; Joseph A. Boscarino, Zahra S. Daar, and Robert E. Smith, Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, Pennsylvania; Yihe G. Daida, Connie Mah Trinacty, Jonathan W. Lai, and Carmen P. Wong, Center for Integrated Health Care Research, Honolulu, Hawaii; and Mark A. Schmidt and Judy L. Donald, The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon.

Author Affiliations: Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC (ACM, JX, PRS, EHT), Atlanta, GA; Henry Ford Health System (LBR, SCG, ML), Detroit, MI; Wayne State University School of Medicine (SCG), Detroit, MI; Geisinger Clinic (JAB), Danville, PA; Kaiser Permanente Northwest (MAS), Portland, OR; Center for Integrated Health Care Research (YGD), Honolulu, HI.

Source of Funding: Henry Ford Health System receives funding for the Chronic Hepatitis Cohort Study (CHeCS) from the CDC and from Gilead Sciences. CHeCS was previously funded through May 2016 by the CDC Foundation, which received grants from AbbVie; Genentech, A Member of the Roche Group; Gilead Sciences; Janssen Pharmaceuticals; and Vertex Pharmaceuticals; past partial funders include Bristol-Myers Squibb. Granting corporations do not have access to CHeCS data and do not contribute to data analysis or writing of manuscripts.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Author Disclosures: Ms Rupp and Dr Lu have received research grant funding to their institution from Gilead Sciences and Intercept Pharmaceuticals and have received travel support from Gilead and Intercept to present posters at The Liver Meeting 2018, sponsored by the American Association for the Study of Liver Diseases. Dr Gordon has received grant/research support from AbbVie Pharmaceuticals, Conatus, CymaBay, Gilead, Intercept, and Merck; has received speaking and lecture fees from Dova Pharmaceuticals; is an ad hoc advisory board member for Dova and Intercept; and receives royalties from UpToDate. Dr Boscarino has received grants from Gilead and Intercept. Dr Schmidt has received institutional research grant support from Gilead and Intercept. Dr Daida reports that her institution received a grant from Gilead to support the submitted work. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (ACM, JAB, MAS, YGD, EHT); acquisition of data (ACM, LBR, SCG, ML, JAB, MAS, YGD, EHT); analysis and interpretation of data (ACM, JX, PRS); drafting of the manuscript (ACM, PRS, JAB, EHT); critical revision of the manuscript for important intellectual content (ACM, JX, LBR, SCG, ML, PRS, JAB, MAS, YGD, EHT); statistical analysis (ACM, JX); provision of patients or study materials (LBR, SCG, ML, JAB); obtaining funding (LBR, SCG, ML, JAB, EHT); administrative, technical, or logistic support (ACM, JAB, EHT); and supervision (JAB, EHT).

Address Correspondence to: Anne C. Moorman, MPH, Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC, Mailstop G-37, Atlanta, GA 30329. Email:

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