Follow-Up Testing for Hepatitis C Virus Infection: An Analysis of Massachusetts Surveillance Data, 2007–2010

Abstract

The Massachusetts Department of Public Health (MDPH) identified cases of hepatitis C virus (HCV) infection reported from 2007 through 2010 to assess evidence of appropriate follow-up testing for the diagnosis of active HCV infection. Surveillance data were used to assess the number of people with reported HCV who had an antibody test and nucleic acid test (NAT) for HCV, to determine the time between tests, and to identify demographic characteristics. Out of the 34,005 cases of HCV reported with laboratory results during the study period, 45% (n=15,279) had only an antibody test reported and 55% (n=18,726) had a NAT reported, with differences by age, gender, and region of residence. Nearly half of those with reported cases of HCV infection in Massachusetts did not have a NAT reported to MDPH, indicating that these individuals may not have received appropriate diagnostic testing. Analysis of demographics suggests differences by age, gender, and region.

Hepatitis C virus (HCV) infection is a major public health concern in the United States, with as many as 5.2 million people affected.¹ It is a major cause of morbidity and mortality and a leading cause of hepatocellular carcinoma. HCV-related mortality has now surpassed that of human immunodeficiency virus-related mortality in the U.S.² While available treatment may reduce mortality,³ HCV-infected individuals first need to be tested appropriately and have active infection confirmed.⁴ In 2009, the American Association for the Study of Liver Disease recommended that a positive screening test for antibodies against HCV should prompt a nucleic acid test (NAT) to confirm active infection and determine if treatment is warranted.⁵ The standard screening test for HCV infection is an enzyme-linked immunoassay (EIA), which detects anti-HCV antibodies in the blood; the most accurate test for identification of current HCV infection is the NAT, which detects HCV ribonucleic acid (RNA) in the blood. Recognition that risk-based screening for HCV infection had not been identifying a sufficient portion of those at risk led the Centers for Disease Control and Prevention (CDC) to recommend routine, one-time-only screening of everyone in the U.S. born between 1945 and 1965,⁶ the major cohort of people diagnosed as having chronic HCV infection.

We conducted an analysis of surveillance data to determine how many of those with HCV infection reported to the Massachusetts Department of Public Health (MDPH) from 2007 through 2010 could be documented to have received appropriate follow-up testing. We examined the time to NAT follow-up testing and the demographic characteristics of those who did and did not receive such follow-up testing.

METHODS

In Massachusetts, all laboratory results indicative of HCV infection are reportable to MDPH. Reports are received via electronic laboratory reporting, faxed reports, and one-page optical character recognition forms called TeleForms^® (HP Autonomy, Sunnyvale, California), all of which are entered into the Massachusetts Virtual Epidemiologic Network (MAVEN), MDPH's secure, Web-based, electronic surveillance system.

For this analysis, data on individuals with evidence of past or current HCV infection were extracted from MAVEN and analyzed using SAS^® version 9.3.⁷ Laboratory tests coded by Logical Observation Identifiers Names and Codes (LOINC^®, the Regenstrief Institute, Inc., Indianapolis, Indiana) and Systematized Nomenclature of Medicine (The International Health Terminology Standards Development Organisation, Copenhagen, Denmark) were categorized based on test type and MDPH's disease classification protocol, which accords with CDC case classifications.⁸ EIA, recombinant immunoblot assay (RIBA), and signal-to-cutoff ratios were included in the antibody test category, while RNA (quantitative and qualitative) and genotype tests were considered NATs. Negative test results are not routinely reported to MDPH, although they may be received with viral hepatitis test panels, where at least one other test on the panel is positive.

People with current or past HCV infection who have an event date (i.e., date of onset of symptoms, specimen collection date, test result date, or report date—whichever was earliest) from January 1, 2007, to December 31, 2010, were included and followed through December 31, 2012. We calculated the time between the first antibody test and the first NAT, if reported, using specimen collection dates. People in this category who had missing laboratory results or specimen dates were excluded from our analysis (n=148, <1%).

We compared people with HCV infection who had a reported NAT with those without a reported NAT by age group (<35 years or ≥35 years of age), gender, and region of the state (West, Central, Northeast, Boston Metrowest, Boston Inner Suburbs, Boston, or Southeast). As a supplemental analysis, we used a logistic regression model to examine the odds of having a reported NAT in relation to region, controlling for gender and age group. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using SAS.

RESULTS

From 2007 through 2010, MDPH received 72,478 laboratory reports indicating past or current HCV infection on 34,005 individuals. Of the 34,005 individuals, 45% (n=15,279) had only a screening or supplementary antibody test(s) reported but no NAT (this proportion was constant during each year of the study period), and 55% (n=18,726) had a NAT, with or without an antibody test reported (Figure).

Figure.

Laboratory results for reported cases of HCV infection in Massachusetts, 2007–2010

^aGenotype testing was included in the NAT category.

^bFor all cases, the earliest specimen date available for each test category was used.

HCV = hepatitis C virus

NAT = nucleic acid test

The Table shows the characteristics of study subjects with antibody-only results and those with NAT results. A lower percentage of people aged <35 years had a NAT reported than those aged ≥35 years (49% vs. 59%). Females and males in both age groups had similar results, with 57% of females and 59% of males having a NAT reported (Table). An analysis of factors associated with having a NAT revealed that among both age groups, after adjusting for gender, several regions of residence had significantly decreased odds of NATs compared with results for the region with the highest proportion of NATs reported (Boston Metrowest), particularly in the Southeast region of the state (<35 years of age: OR=0.55, 95% CI 0.45, 0.67; ≥35 years of age: OR=0.71, 95% CI 0.61, 0.82). Females aged ≥35 years also had decreased odds of having a NAT (OR=0.87, 95% CI 0.82, 0.93) compared with their male counterparts (data not shown).

Table.

Demographic characteristics of people with only a reported HCV antibody test and those with any reported NAT in Massachusetts, 2007–2010

^an=2,490 missing gender

^bn=6,244 missing region

HCV = hepatitis C virus

NAT = nucleic acid test

DISCUSSION

With 8,000–10,000 cases of HCV infection reported to MDPH annually, hepatitis C is one of the most common reportable diseases in Massachusetts. We found that for nearly half of all cases, MDPH had never received results of the recommended follow-up NAT, which determines active infection. We therefore cannot determine whether these cases were of past (resolved) HCV infection or current active infection, and these results suggest that many of the infected individuals did not receive appropriate follow-up testing. These results are very similar to those in a recent CDC report, which was based on data from eight jurisdictions.⁹ CDC reported that 49% (n=107,209) of all people with newly reported HCV cases had only an antibody test reported, 59% of whom were born between 1945 and 1965.⁸ We also found differences by age group in whether or not MDPH had received a NAT report.

Most people reported to MDPH to have HCV infection are males aged ≥35 years, with residence relatively evenly distributed across the state. These reports are generally of cases of chronic HCV infection, likely with exposure in the 1970s and 1980s, when incidence rates of HCV infection were high.^6,9 Recently, an epidemic of HCV infection has been identified among young injection drug users aged 15–25 years.¹⁰ In our analysis, people with HCV infection who were <35 years of age had a lower percentage of reports of NATs than those aged ≥35 years. Females had a slightly lower percentage of reported NATs than males, particularly among those aged ≥35 years. There were differences by region of the state in reports of NATs, even after controlling for age and gender. We hypothesize that the younger members of the group may not be seeking the follow-up care that their older counterparts are receiving. This lack of follow-up may be due to provider factors (e.g., access to care, awareness, or failure to obtain a risk history prompting confirmation of test), less overall health-care utilization, continued drug use, or not having received the initial positive antibody test result. In addition, among individuals with a documented NAT after antibody testing, 16% did not receive such testing until at least two years later, implying delay in diagnosis, care, and potential treatment.

Limitations

This study was subject to several limitations. Because this analysis was based on surveillance data, it is reliant only on information in reports to MDPH. As in other jurisdictions, we do not typically receive reports of negative NATs,⁹ but we expect that most individuals with a positive anti-HCV antibody test would have evidence of active infection by NAT. In a study of 47,041 EIA-repeat-reactive blood donations, 79% of those that were RIBA positive were also NAT reactive.¹¹ We were also unable to analyze MDPH surveillance data by clinical care provider type or location, so we could not determine how provider type or setting may impact testing. Additionally, the analysis of factors associated with having a NAT was limited due to a large proportion of infected people with missing race/ethnicity information; thus, potential racial/ethnic disparities could not be examined.

CONCLUSION

Our results mirror those in a recent CDC report, which found that almost half of all newly reported people with HCV infection in eight U.S. sites during 2005–2011 were HCV antibody positive only.⁹ As new medications become available, HCV infection is becoming increasingly treatable and even curable.^3,12 Successful treatment has been shown to be cost effective, decreasing morbidity and mortality associated with HCV infection.^3,13 However, if patients do not receive complete evaluation for active infection, they cannot engage in appropriate care and receive the benefit of treatment. Enhanced diagnostic services and education for health-care providers and people at risk of infection would serve to improve screening, diagnosis, and access to care.