Hepatitis C screening in commercially insured U.S. birth-cohort patients: Factors associated with testing and effect of an EMR-based screening alert

Introduction

Chronic hepatitis C virus (HCV) infection is a common cause of death from liver disease, and a leading indication for liver transplantation.[1] An estimated 3.2 million people are living with HCV in the United States.[2] With the new direct-acting antivirals, most HCV-infected patients could potentially be cured of their disease.[3] However, many people living with HCV infection are unaware of their infection status.[4] As a result, the disease remains under-diagnosed and undertreated.

In 1998, the CDC recommended HCV testing for certain high-risk populations, including injection drug users, recipients of transfusions or transplants prior to 1992, patients on hemodialysis, health care and public safety workers with needle stick or mucosal exposure to HCV-infected blood, children born to HCV-positive women, and patients with abnormal liver tests[5]. However, risk-based HCV testing was found to miss more than half of all infected persons. Among participants in the NHANES survey, only seven per cent of HCV-infected persons reported having been tested based on known risk factors for HCV,[4] and only 45% to 85% of HCV-infected persons had been tested for HCV.[6,7,8]

Subsequent studies demonstrated a significantly increased prevalence of HCV infection in persons born between 1945 through 1965. This cohort, subsequently named ”baby boomers” or birth-cohort, accounts for more than three quarters of all HCV infections and HCV-related deaths in the United States.

Consequently, the CDC recommendations were amended to include HCV Ab testing in all birth-cohort patients, in addition to risk-based testing.[9] According to a CDC estimate, the implementation of this recommendation would result in the identification of an additional 800,000 persons who are currently unaware of their HCV status. With proper linkage to care, this measure could prevent more than 120,000 HCV-related deaths.[10] In accordance with the CDC recommendation, the United States Preventive Services Task Force in June 2013 endorsed one-time HCV antibody testing in all birth-cohort patients, regardless of their risk profile.[11]

In general, HCV screening rates in birth-cohort patients have remained low. A study of over 25,000 baby boomer patients enrolled in the Kaiser Permanente Mid-Atlantic States’ (KPMAS) health system revealed that 14.4% had been HCV antibody-tested between 2003 and 2012.[12] More recent quality improvement studies reported testing rates of 11% to 47.2%.[13,14]

Although HCV testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing.The aims of our study were to analyze factors associated with overall HCV-Ab testing in a large birth-cohort population, to determine true birth-cohort testing rates, and to evaluate the impact of a new EMR-based BPA on HCV screening in our hospital system.

Methods

Results

Study Population 1

The total study population comprised 106,753 subjects, 11,976 of whom underwent HCV-Ab testing and 670 tested positive.Table 1 shows a stratification of the patients according to their demographic characteristics.

Table 1

Demographics of Study Population 1

Demographic characteristics	HCV AB tested		Grand total
	N	(%)	N	(%)
Total	11,976	(100%)	106,753	(100%)
Age
Average (SD)	59.7	(5.8)	59.7	(5.9)
50-64	9,101	(76%)	79,198	(74%)
65-79	2,875	(24%)	27,555	(26%)
Gender
Female	7,056	(59%)	61,789	(58%)
Male	4,920	(41%)	44,964	(42%)
Race
African American	1,213	(10%)	5,905	(6%)
American Indian	30	(0%)	271	(0%)
Asian	705	(6%)	4,531	(4%)
Caucasian	7,419	(62%)	72,154	(68%)
Other	2,609	(22%)	23,892	(22%)
Ethnicity
Unknown	9	(0%)	174	(0%)
Hispanic/Latino	658	(5%)	4,252	(4%)
Non-Hispanic	11,309	(94%)	102,327	(96%)

Figure 1 shows the influence of demographic characteristics on the prevalence HCV-Ab testing. Testing was more frequent among patients within the age range of 50 – 64 years as compared to patients aged 65 – 79 years. Similarly, females were slightly more likely to be tested than males. Although statistically significant, these differences between the subgroups were small. More substantial differences were noted with regard to ethnicity and race, as African Americans, Asian, and Hispanic patients were more frequently tested than self-classified Causasians, American Indians, or Non-Hispanics. HCV-Ab testing was also more frequently performed in patients with a variety of comorbid conditions (Figure 2). The two conditions most frequently associated with HCV-Ab testing were HIV infection and chronic kidney disease. Table 2 shows the results of the multivariate analysis, using the presence of HCV antibody test as outcome variable and demographic characteristics and comorbid conditions as predictor variables. The results of the multivariate analysis largely confirmed the results of the univariate analyses depicted in Figures 1 and 2. Figure 3 contains a comparison of the medical sub-specialties amongst all primary care physicians and amongst the physicians, who ordered the HCV antibody testing. Each subspecialty is expressed as percentage of all physicians providing primary care and as percentage of all ordered HCV tests. Internal Medicine and Family Medicine clinics performed most of the tests but were relatively underrepresented amongst the ordering physicians as compared to the subspecialists. High frequencies of test orders were associated with gastroenterology and rheumatology specialty clinics.

Figure 1

Influence of demographic characteristics on HCV antibody testing. Age, sex, race and ethnicity all exerted statistically significant influences.

Figure 2

Influence of comorbid conditions on HCV antibody testing. Except for dementia, all comorbid conditions exerted a statistically significant influence. CKD: chronic kidney disease; COPD: chronic pulmonary obstructive disease; HIV: human immune deficiency virus infection; PVD: peripheral vascular disease.

Table 2

Logistic fit for HCV antibody testing

Predictor variable	Odds ratio	95% Confidence interval	p-value
Age-Sex
Younger age[∗]	1.20	(1.12-1.29)	<0.0001
Female	0.94	(0.91-0.98)	0.0035
Race
African American[∗∗]	1.96	(1.82-2.10)	<0.0001
American Indian	1.00	(0.67-1.44)	0.5836
Asian	1.65	(1.51-1.79)	<0.0001
Other	1.01	(0.96-1.06)	0.6022
Ethnicity
Hispanic	1.52	(1.38-1.66)	<0.0001
Comorbidity
Diabetes	1.44	(1.36-1.52)	<0.0001
COPD	1.55	(1.35-1.77)	<0.0001
Psychosis	1.42	(1.01-1.95)	0.0416
Dementia	1.26	(0.72-2.08)	0.4045
HIV	16.77	(11.32-25.35)	<0.0001
CKD	3.64	(3.15-4.21)	<0.0001
Cancer	1.55	(1.33-1.80)	<0.0001
Depression	1.50	(1.42-1.58)	<0.0001
Hypertension	1.12	(1.07-1.17)	<0.0001
PVD	1.21	(1.01-1.45)	0.0352
Asthma	1.18	(1.09-1.27)	<0.0001

1. For the overall model: N = 106,751, chi-square = 1,847 (df = 18, P<0.0001). CKD: chronic kidney disease; COPD: chronic pulmonary obstructive disease; HIV: human immune deficiency virus disease; PVD: peripheral vascular disease.

Figure 3

Comparison of medical sub-specialty amongst all primary care physicians (PCP) and amongst physicians ordering HCV antibody testing (chi-square 25 277, df= 13, P< 0.0001).

Impact of HCV-BPA on age cohort testing

HCV testing rates were increased from 0.68% (69/10,089) pre-BPA to 10.76% (5451/45188) during the four months following the system-wide implementation of the BPA, corresponding to a 15.8-fold increase (Figure 4). The difference between the two rates was statistically highly significant (P<0.0001).

Figure 4

Comparison of HCV screening rates in age cohort patients before and after the implementation of an EMR-based BPA (chi-square 1033.32, df =1,P<0.0001).

Discussion

Our study highlights some of the challenges and limitations of HCV birth-cohort testing. While conceptually straightforward, the systematic implementation of testing in this high-risk group has been difficult to achieve in many US healthcare systems, with the notable exception of the Veterans Associations HCV Initiative, which has resulted in screening rates of over 50%.[15]

In our population of over 100,000 commercially insured baby boomers, the overall HCV-Ab testing rate was 11.2%, suggesting a modest but meaningful implementation of the current HCV screening guidelines.

However, a closer analysis of the data provided clear evidence that the historic testing rates were predominantly due to the presence of real or perceived risk factors, including ethnic and racial factors, comorbidities, and other medical and demographic features. Several of these factors have been previously reported. For example, disproportionately high screening rates in African-American and Hispanic patients were previously reported in a large patient cohort in Southeast Michigan,[16] and in the Veterans Affairs patient cohort of over five million individuals.[17] With regard to gender, testing rates in women have been found to be higher than in men in some [18] but not all studies.[19,20] The association of high testing rates in patients with HIV infection[21] and chronic renal disease[22] are not surprising in view of the increased exposure risk in these groups. The modest but significant association with a number of other comorbidities, including diabetes,[23] chronic pulmonary disease,[24] psychiatric disease,[25] cancer,[26] hypertension,[27] may be related to possible extrahepatic manifestations of HCV, or may reflect higher rates of healthcare utilization in patients with chronic diseases.

These confounding data prompted use to determine the true birth-cohort screening rates in our health care system. To this end, we analyzed all patients who presented to their primary care offices during the month of July, 2015. Of note, this date corresponded to a time period approximately three years after the recommendation for universal baby boomer screening by the CDC, and two years following the endorsement by the U.S. Preventive Services Task Force (USPSTF).

Strikingly, only 1.3% of all eligible birth-cohort patients in this group underwent HCV Ab testing, and the majority (0.7%) of patients were tested based on the presence of risk factors or abnormal liver tests. Only 0.6% of patients underwent “true birth-cohort testing”, more than one order of magnitude below the overall historic testing rate in institution.

Due to the small numbers of individuals tested, we were unable to perform a statistically meaningful comparison of testing rates by primary care, family practice, or medical subspecialty physicians. However, since primary care and family practice accounted for approximately 97% all patient visits, we can predict that a major improvement in HCV screening will require higher implementation rates in these two clinics. In comparison, the contribution of subspecialty clinics will be limited.

While sobering, our results are well within the range of comparable studies in the US. For example, Isenhour and colleagues recently reported an overall HCV Ab testing rate of only 3.26% in a population of over 24 million enrollees from Truven Health’s MarkedScan Commercial and Medicare Supplemental insurance claims database. They noted a significant, 91% increase in testing rates between 2011 and 2014, but concluded that “testing remains suboptimal”.[28]

The poor adherence to sensible and validated screening guidelines does not appear to be limited to HCV, but may be a general feature of primary care medicine. Multiple barriers to implementation have been identified. They include personal characteristics, guideline features, and external factors influencing the physician’s decision in favor of or against screening at the point of care.[29]

Approaches to improve HCV screening rates have been widely discussed in the recent literature. They include the creative use of electronic medical record-based alerts.[30,31] For example, Lok and colleagues recently reported the successful implementation of an electronic medical record-based “Best Practice Alert”.[32] This alert automatically identified birth-cohort patients who had not been screened, and prompted the clinic physician to order the HCV Ab test at the point of care. This intervention, coupled with educational materials for patients and providers, increased screening rates approximately 10-fold, from 7.6 to over 72 per cent. Similar improvements have been reported in a recent study by Klausner and colleagues.[33] We used a similar approach by introducing a BPA into our healthcare system’s EMR (“EPIC”), and observed a 15-fold increase in screening rates. Assuming a sustained testing rate of 10% per patient visit, and biannual primary care clinic visits for the majority of patients, the cumulative testing rate in our patient population would approach 65% over a 5-year BPA span. Achieving a cumulative rate of 89% would require a doubling of the per-visit rate to 20%, a target that we consider achievable.

In summary, our findings demonstrate that true birth-cohort-based HCV testing is infrequently performed in our health care system. Our study highlights the suboptimal implementation of current HCV birth-cohort screening guidelines, and provides a rationale for quality improvement initiatives to address this important public health challenge.

Source of Foundation

The research reported in this manuscript was funded through an educational grant from Gilead Sciences Inc, ISR grant IN-US-342-4105.