HCV screening and prevalence estimates, unadjusted and adjusted for HCV risk factors, are examined in this 8-year observational study of a managed care organization.
The Centers for Disease Control and Prevention recommends routine screening for the hepatitis C virus antibody (anti- HCV) among persons most likely to be infected. Little is known about anti-HCV screening and prevalence in routine practice settings. We studied anti-HCV screening rates, anti-HCV positivity, and demographic and risk factors associated with increased likelihood of anti-HCV screening or positivity in a managed care organization (MCO).
This was a retrospective observational study of 17-to-74-year-old MCO enrollees from 2000 to 2007 (N = 557,056; 1,949,499 enrollee years). The primary outcome measures were likelihood of anti-HCV screening and HCV positivity (both in the total population and among those screened). Independent variables were: birth cohort, gender, HCV risk factors, and socioeconomic status (SES) and race of residents’ neighborhoods. Likelihood of each outcome as a function of the independent variables was estimated using logistic regression.
Over the 8-year period, 4.31% of the total population received anti-HCV screening; 0.22% had a positive HCV result. Among those screened, HCV positivity was 5.15%. HCV screening and positivity rates increased over time. Both likelihood of HCV screening and HCV positivity were highest (P <.05) among persons born during 1945-1964, males, those with HCV risk factors, and residents of neighborhoods of lower SES or with higher percentages of African Americans.
Although HCV screening and detection improved in this MCO over an 8-year period, anti-HCV screening was lower than expected. Many persons at risk for HCV remained unscreened. Strategies for improving anti-HCV screening in routine practice are recommended for patients at increased risk.
(Am J Manag Care. 2011;17(8):548-555)
A study was performed of HCV screening and prevalence estimates in a managed care organization, unadjusted and adjusted for HCV risk factors.
According to an Institute of Medicine report released in 2010, hepatitis C virus (HCV) infection is a serious public health concern.1 In liver transplant centers in the United States, HCV infection has been found to be the most frequent risk factor for liver cancer.2 Incidence rates of hepatocellular carcinoma in the United States have tripled from 1975 to 2005,3 and have increased at an average annual rate of 3.5% from 2001 to 2006.4 Five-year survival rates for liver cancer are less than 15%,3 and more than 35,000 incident deaths are forecast to be attributable to HCV by 2030 given the aging of the population with chronic HCV infection.5
A study of HCV infection prevalence in the United States using the 1999-2002 National Health and Nutrition Examination Survey (NHANES) estimated that 1.6% of the non-institutionalized non-homeless US population had measurable antibody to HCV (anti-HCV).6 HCV prevalence was significantly higher among specific demographic groups (persons born 1945-1964 [“high prevalence birth cohort”]), males, individuals with specific behavioral risk factors (injection drug use [IDU]), medical and behavioral characteristics associated with HCV infection (elevated serum alanine aminotransferase [ALT] levels, HIV (human immunodeficiency virus) infection, blood transfusion before 1992, higher numbers of lifetime sexual partners), and those with selected socioeconomic characteristics (high school education or less, income below the poverty threshold). Screening among a random sample of Veterans Administration (VA) medical center users indicated that HCV positive rates were approximately 5.4%.7
Since 1998, the Centers for Disease Control and Prevention (CDC) has recommended that screening for anti-HCV should be routinely offered to persons most likely to be infected with HCV.8 Yet, little is known about anti-HCV screening practices and HCV infection prevalence in routine practice settings. Analysis of UnitedHealthcare medical claims from 1997 to 1999 indicated that 0.7% of enrollees were ever screened for HCV and, of those, 6.7% were HCV-positive (approximately 0.08% of the enrollee population).9 This HCV infection prevalence was much lower than that detected in the NHANES and VA studies and suggests that current anti-HCV screening practice may fail to detect many infected persons who could benefit from primary and secondary prevention counseling and medical management.
Both provider and patient factors might influence anti-HCV screening in routine practice. Physicians frequently do not collect HCV risk factor information from new patients; and, even if a patient has a risk factor, providers often do not order anti-HCV screening tests.10-13 Patients may not admit to stigmatizing behaviors, such as IDU, that might prompt providers to screen.14,15 Consequently, the majority of HCV-infected adults are most likely unaware of their infection and therefore do not seek out appropriate treatment or prevention services.16-19
To assess how CDC recommendations for anti-HCV screening are currently implemented in a typical healthcare setting, we conducted a retrospective observational study of HCV screening and HCV infection prevalence among adult enrollees of a managed care organization (MCO) from 2000 through 2007. Our study had 2 objectives: to estimate 1) cumulative rates of anti-HCV screening and positivity in this MCO, and 2) association of enrollee demographic and risk factors with likelihood of anti-HCV screening and positivity.
Kaiser Permanente Georgia (KPG) is a federally qualified, group- and network-model MCO that, during the study period, provided comprehensive medical services to approximately 275,000 members per year in the metropolitan Atlanta area. This study protocol was reviewed and approved by the KPG Institutional Review Boards (IRBs) and CDC.
Practice Guidelines for HCV Screening
KPG’s clinical practice guidelines recommend enzyme immunoassay (EIA) for anti-HCV screening, with confirmation by reverse transcriptase—polymerase chain reaction if the initial screening test is reactive. These guidelines recommend anti-HCV testing according to “risk for infection” including: IDU history or other illegal drug use, history of chronic hemodialysis, persistently abnormal ALT levels, receipt of clotting factor concentrate before 1987, and receipt of blood transfusion or organ transplant before July 1992.
KPG computerized databases were the source of data for enrollee demographics, enrollment history, laboratory screens and results, and diagnoses and procedures (both International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]-coded and Current Procedural Terminology, 4th Edition [CPT-4]-coded) associated with ambulatory, emergent, and hospital care. All records can be linked at the individual level using unique identifiers. Residential addresses of KPG enrollees are geocoded to US Census tracts and block groups using MapMaker Plus (Mapinfo, Troy, New York) for linking to Summary File 3 (SF3) records.
The study population consisted of 557,056 enrollees, aged 17 to 74 years, impaneled to a KPG primary care physician, and enrolled at least 1 month during 2000-2007. The population was constructed year by year, with age defined as of January 1st of each year. Thus, an enrollee who was 17 to 74 years of age as of January 1st of a year and enrolled for at least 1 month during that year would be included for that year. An enrollee <17 years or >74 years as of January 1st of a year or an enrollee without enrollment in a year would not be included for that year. Thus, the final analysis data set included 1,949,499 enrollee-years.
HCV Screening. HCV screening was defined as having had an HCV antibody laboratory assay performed, either an anti-HCV EIA or recombinant immunoblot assay (RIBA). HCV RNA assays, for quantitative measurement of viral load, were not considered to be screening tests in this study.
Annual and cumulative anti-HCV screening rates were defined. For tracking annual rates of HCV screening, each age-eligible enrollee with enrollment in a study year was ascertained for receipt of at least 1 anti-HCV screening test in that year. History of anti-HCV screening for each enrollee was then assessed across the 8-year period to determine if the enrollee was “ever screened.”
HCV Positivity. HCV positivity was defined as an indication in the laboratory records of a positive result on an anti-HCV screening test. Annual and cumulative anti-HCV positivity rates were defined similar to HCV screening.
Neighborhood Socioeconomic Status Index. A neighborhood socioeconomic status (SES) index is defined from principal components analysis of 7 of the 2000 SF3 variables for each enrollee’s geocoded Census tract or block group (518,639 of the 557,056 enrollees in the study population): 1) Percent of households with income below the poverty level, 2) Percent of households receiving public assistance, 3) Percent of households with annual income below $30,000, 4) Percent of working age adult males not in the labor force, 5) Percent of adults 25 years and older with a high school education or less, 6) Log of median household income, and 7) Log of median value of single family homes. The selected variables are based on previous studies.20,21 Factor scores obtained from the principal components analysis are used to assign enrollees to quartiles of an SES index.
Percent African American Residents in Neighborhood. Percent of African American residents in a neighborhood was also obtained from the 2000 SF3 data set for each enrollee’s geocoded Census tract or block group. This variable serves as a proxy measure for race since individual-level race is not generally available. Internal KPG studies show a significant positive correlation at the Census tract level between self-report from surveys and this SF3 measure (Pearson coefficients >0.80).
Covariates. In addition to these 2 area-based measures, individual-level covariates were defined for duration of enrollment during 2000-2007 (<1, 1-2, 3-4, and >4 years), selected HCV risk factors, and birth cohort. Given the potential confusion caused by differences in terminology regarding behavioral risk factors, medical risk markers, and healthcare and environmental exposures, we consolidate these categories under the single term risk factors for the sake of brevity in the narrative. HCV risk factors were defined for IDU, coagulation defects (eg, hemophilia), dialysis, HIV, and elevated ALTs (, available at www.ajmc.com). These measures were selected because they were 1) listed as indications for HCV screening in KPG’s clinical practice guidelines or referenced in the provider focus groups and 2) could be measured using KPG computerized data beginning with 1995 (the first year for which reliable and complete computerized data were available). Other HCV risk factors (eg, blood transfusions prior to 1992) were not measured due to incomplete data prior to 1995. Birth cohorts were defined by year of birth and classified into 5-year subgroups.
For 2000-2007, we graphed the annual anti-HCV screening and HCV positivity rates per 10,000 enrollees both for the high-prevalence cohort and those born before 1945 or after 1964. We used a χ2-statistic to test for significance (P <0.05) of associations of each covariate with the percent of the study population: 1) ever screened for HCV, 2) ever screened positive for HCV from 2000 to 2007, and 3) ever screened positive among those screened. We also estimated multiple logistic regression models for these 3 outcomes as a function of enrollment duration, birth cohort, gender, quartiles of neighborhood SES and percent African American residents, and the 5 HCV risk factors available in the medical record. In addition to the models with the HCV risk factors separately specified, we estimated another set of models with a single measure of HCV risk (any of the 5 vs none) in place of the 5 separate risk factors.
displays the annual HCV screening rate per 10,000 age- and enrollment-eligible adults. On average, the annual HCV screening rate increased approximately 3-fold from 2000 to 2007. The annual HCV screening rate trends differed only slightly between the high prevalence birth cohort and the other birth cohorts.
displays the annual HCV positive rate per 10,000 age- and enrollment-eligible adults. The annual HCV positive rate remained relatively constant until 2004, when the rate increased by about 30% for all ages. Over the 8 study years, the ratio of HCV positivity of the high prevalence birth cohort to those outside the cohort averaged 5.0, with a range of 4.0 (2001) to 7.3 (2003).
Approximately one-third of the study population represented the high prevalence birth cohort; and, approximately one-third of the population was enrolled with KPG for 4 or more years of the study period (). There were slightly more women than men. Documented HCV risk factor prevalence was generally low; and, only 2.67% of the population had 1 or more of the 5 recorded risk factors.
Over the 8 year period, 4.31% of the total population was ever screened for HCV; 0.22% of the population ever screened positive for HCV; and, among those screened, 5.15% had a positive anti-HCV test (Table 1). Frequency of anti-HCV screening and HCV positivity (both within the entire study population and among those screened) were significantly associated with 4 or more years of enrollment, birth between 1945 and 1964, males, enrollees living in lower SES neighborhoods or neighborhoods with a high percentage of African American residents, and 1 or more of the 5 recorded risk factors.
displays the adjusted odds ratios (aORs) from the multiple logistic regression models. Generally, the pattern of the aORs with respect to the covariates was similar to the pattern observed in the unadjusted associations (Table 1); however, there were some differences. The likelihood of ever being screened for HCV was generally higher among those who had longer enrollment duration, were younger, were females, lived in the highest SES neighborhoods or neighborhoods with high percentages of African Americans, or had any of the documented HCV risk factors. The likelihood of ever being screened positive for HCV was generally higher among those who had longer enrollment duration, were born from 1945 to 1964, were male, lived in the lowest SES neighborhoods or neighborhoods with high percentages of African Americans, or had any of the recorded HCV risk factors. This pattern of aORs for ever screened HCV positive with the covariates was also observed among the subgroup ever screened for HCV (with the exception of the distribution of aORs for enrollment duration). In the multiple logistic regressions with a variable for any of the 5 documented HCV risk factors (vs none) in place of the 5 separate risk factors, significant (P <0.05) positive associations were again observed with HCV screening and HCV positivity.
For the multiple logistic regression models which grouped the 5 documented HCV risk factors into a single measure, we found significant, positive associations with HCV screening and HCV positivity—with aORs of 8.21 for ever being screened for HCV, 15.22 for ever being screened HCV positive, and 2.84 for ever being screened HCV positive among those ever screened.
displays the association of the prevalence of individual risk factors with neighborhood SES, percent of neighborhood residents who are African American, and birth cohort. HIV, injection drug use, and dialysis were more prevalent in areas of low SES and high percentages of African American residents. In contrast, prevalence of elevated ALT was higher in high SES neighborhoods and areas with low percentages of African American residents. Some risk factors (injection drug use, HIV) were highest in the high prevalence cohort (those born 1945-1964); other risk factors (coagulation defects, dialysis, elevated ALT) had a significant association with age.
Over an 8-year period, 4.31% of adults at this MCO were screened at least once for HCV. This is considerably higher than the 0.7% of adults who were screened for HCV in a previous study in a managed care setting.9 Furthermore, HCV screening rates in this MCO increased approximately 3-fold from 2000 to 2007. While it is unclear why these rates have been increasing, these results are consistent with the findings from our focus groups with providers where gastroenterologists shared their impression that primary care physicians were ordering more HCV screening tests when patients had elevated ALTs.
Consistent with risk-based recommendations, providers in this MCO were more likely to screen adults with known HCV risk factors than those without. HCV screening was highest among the high prevalence birth cohort and those who exhibited specific HCV behavioral risk factors or medical markers, such as IDU, HIV, and elevated ALTs. These results likewise were consistent with comments from providers in the focus groups who noted both common HCV risk associations (eg, HIV, IDU, multiple sex partners) and less common associations (eg, “likely exposure to other people’s blood, as with military service,” “irritable bowel syndrome, since people with this condition have a history of substance abuse in their past,” and “place of birth”) for ordering anti-HCV screening. Nevertheless, the proportion of persons screened for anti-HCV is low considering the CDC risk-based screening recommendations, as only 29% of adults with at least 1 of the 5 identifiable HCV risk factors had anti-HCV screening.
In the focus groups, KPG providers acknowledged selective anti-HCV screening. IDU status was assessed “when relevant.” Providers might skip HCV screening among adults reporting IDU if that use was “one-time” or “in the distant past.” Providers expressed a reluctance to recommend anti-HCV screening because “the treatment can be worse than the disease.”
The ratio of HCV positivity in the high-prevalence cohort to all others in the study population averaged 5.0, with a range of 4.0 (2001) to 7.3 (2003). This is similar to the 4.6 ratio found in NHANES (1999-2002; unpublished CDC data), and the 4.0 ratio found among veterans (1998-2000).7 Consistent with studies of HCV prevalence in the national population and in the VA,6,7 HCV positivity was highest among KPG adults born from 1945 to 1964, males, and those with associated risk factors. Neighborhood SES and percentage of African American residents had independent, significant associations with likelihood of being screened HCV-positive—a finding similar to the associations of race and SES with HCV prevalence in the national population.6
During this 8-year period, 0.22% (1226) of this MCO’s adults screened positive for HCV, which is only 14% of the US HCV prevalence estimate of 1.6%.6 Although anti-HCV screening was targeted to adults at high risk of HCV infection, the screening rate was low—only 4.31% of adults—and suggests many adults who might have screened positive for HCV were unrecognized. If we assume that the overall MCO HCV prevalence was similar to the US estimate of 1.6%, then 1.4% (1.6% minus 0.2%) or 7687 MCO adults may have had undetected but positive HCV antibodies from 2000 through 2007. Thus, new strategies, or reinforcement of existing strategies, are needed to improve HCV screening and identification of unknown cases.
It is important to acknowledge some of the limitations of our data and analyses. We studied the adult population in a single MCO from 2000 to 2007. Thus, study findings may not generalize to current HCV screening or HCV positivity in other insured or uninsured populations. The lack of computerized data prior to 1995 limited ascertainment of some important HCV risk factors (eg, blood transfusions prior to 1992). Risk factor status is likely understated. For example, socially undesirable behaviors associated with HCV infection risk are frequently under-diagnosed and under-recorded.15,22 The area-based measures of SES and race likely serve as proxies for either under reported or additional clinical risks associated with SES or race/ethnicity. We did not examine patients’ histories of hepatitis A or hepatitis B vaccination, which are recommended for persons with chronic liver disease and for risk factors that might also have indicated increased risk of HCV positivity.23,24 Provider characteristics (eg, provider tenure with the MCO) might affect attitudes toward HCV screening rates but were not included in analyses.
We considered the possibility that elevated ALTs might represent a response to statin exposure but not HCV infection. Adults in this MCO population with elevated ALTs both with and without statin exposure had significantly elevated risk of HCV positivity (eg, aORs of 13.5 for exposed vs 23.4 for unexposed). This suggests that anti-HCV screening should not be ruled out among statin-exposed adults with significantly elevated ALTs.
In conclusion, increased anti-HCV screening rates in this MCO from 2000 to 2007 (Figure 1) correlated with improved rates of detecting anti-HCV positivity (Figure 2). Nevertheless, even among subgroups at high risk for HCV infection, anti-HCV screening is suboptimal. Efforts to improve rates and timeliness of anti-HCV screening generally and in specific high prevalence subgroups could yield additional benefits by identifying candidates for HCV pharmacotherapy, and lead to a potential reduction in end-stage liver disease, and averted liver transplants or death due to liver failure. Providers in the focus groups recommended 2 key operational strategies to enhance HCV screening: build HCV risk factor assessment prompts into the electronic medical record (EMR) system, and build alerts into the EMR to prompt for anti-HCV screening orders during visits of patients with a documented history of HCV risk factors. Expanding and improving physician education regarding HCV screening criteria and effective strategies to probe for risk factors indicative of possible HCV infection but likely to be under-reported by patients is also warranted.
Since the highest positivity rates in this population occur among those born from 1945 to 1964, the same cohort identified in the NHANES and VA studies, a strategy of screening persons in this high prevalence cohort should be evaluated. A strategy for universal age-driven HCV screening could be relatively straightforward to implement and might improve efforts to find previously unidentified persons with HCV infection.
The authors wish to acknowledge the helpful comments from David Greenstein, MD, and Winkler Weinberg, MD, of Kaiser Permanente Georgia on previous drafts of this manuscript.
Author Affiliations: From The Center for Health Research/Southeast (DWR), Kaiser Permanente, Atlanta, GA; Division of Viral Hepatitis (BDS, CMW, MES), Centers for Disease Control and Prevention, Atlanta, GA.
Funding Source: Work on this project was funded through a grant (200-2008-M-27862) to Kaiser Permanente Georgia from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Author Disclosures: The authors (DWR, BDS, CMW, MES) 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 (DWR, BDS, CMW, MES); acquisition of data (DWR); analysis and interpretation of data (DWR, BDS); drafting of the manuscript (DWR, BDS); critical revision of the manuscript for important intellectual content (DWR, BDS, CMW, MES); statistical analysis (DWR); obtaining funding (DWR, BDS, CMW, MES); and supervision (BDS, CMW).
Address correspondence to: Douglas W. Roblin, PhD, Kaiser Permanente Georgia, 3495 Piedmont Rd, NE, Bldg 9, Atlanta, GA 30305. E-mail: email@example.com.
1. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: Institute of Medicine; 2010.
2. Di Bisceglie AM, Lyra AC, Schwartz M, et al. Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. Am J Gastroenterol. 2003;98(9):2060-2063.
3. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27(9):1485-1491.
4. O’Connor S, Ward JW. Hepatocellular carcinoma—United States, 2001-2006. MMWR. 2010;59(17):517-520.
5. Rein DB, Wittenborn JS, Weinbaum CMW, Sabin M, Smith BDL, Sarah B. Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States. Dig Liver Dis. In press.
6. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705-714.
7. Dominitz JA, Boyko EJ, Koepsell TD, et al. Elevated prevalence of hepatitis C infection in users of United States veterans medical centers. Hepatology. 2005;41(1):88-96.
8. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated chronic disease. MMWR. 1998;47(No. RR-19).
9. Shatin D, Schech SD, Patel K, McHutchison JG. Population-based hepatitis C surveillance and treatment in a national managed care organization. Am J Manag Care. 2004;10(4):250-256.
10. Leverence RR, Williams RL, Pace W, et al. Context of clinical care: the case of hepatitis C in underserved communities--a report from the Primary Care Multiethnic Network (PRIME Net) Consortium. J Am Board Fam Med. 2009;22(6):638-646.
11. Shehab TM, Sonnad SS, Lok AS. Management of hepatitis C patients by primary care physicians in the USA: results of a national survey. J Viral Hepat. 2001;8(5):377-383.
12. Shehab TM, Sonnad S, Gebremariam A, Schoenfeld P. Knowledge of hepatitis C screening and management by internal medicine residents: trends over 2 years. Am J Gastroenterol. 2002;97(5):1216-1222.
13. Zickmund, SL, Brown KE, Bielefeldt K. A systematic review of provider knowledge of hepatitis C: is it enough for a complex disease? Dig Dis Sci. 2007;52(10):2550-2556.
14. Conry-Cantilena C, VanRaden M, Gibble J, et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. 1996;334(26):1691-1696.
15. Sanka P, Jones NL. To tell or not to tell: primary care patients’ disclosure deliberations. Arch Intern Med. 2005;165(20):2378-2383.
16. Brady KA, Weiner M, Turner BJ. Undiagnosed hepatitis C on the general medicine and trauma services of two urban hospitals. J Infect. 2009;59(1):62-69.
17. Hagan H, Campbell J, Thiede H, et al. Self-reported hepatitis C virus antibody status and risk behavior in young injectors. Public Health Rep. 2006;121(6):710-719.
18. Kwiatkowski CF, Fortuin Corsi K, Booth RE. The association between knowledge of hepatitis C virus status and risk behaviors in injection drug users. Addiction. 2002;97(10):1289-1294.
19. Volk ML, Tocco R, Saini S, Lok AS. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6): 1750-1755.
20. Singh GK, Miller BA, Hankey BF, Feuer EJ, Pickle LW. Changing area socioeconomic patterns in U.S. cancer mortality, 1950-1998: Part I: all cancers among men. J Natl Cancer Inst. 2002;94(12):904-915.
21. Singh GK, Miller BA, Hankey BF. Changing area socioeconomic patterns in U.S. cancer mortality, 1950-1998: Part II: lung and colorectal cancers. J Natl Cancer Inst. 2002;94(12):916-925.
22. Saitz R, Mulvey KP, Plough A, Samet JH. Physician unawareness of serious substance abuse. Am J Drug Alcohol Abuse. 1997;23(3): 343-354.
23. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-23.
24. Mast EE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55(RR-16):1-33.