July 24, 2013

Z. M. Younossi, M. Stepanova, M. Afendy, B. P. Lam, A. Mishra

J Viral Hepat. 2013;20(8):550-555.

Abstract and Introduction
Abstract

HCV is the leading cause of cirrhosis and liver cancer in the U.S. The Center for Disease Control (CDC) has recently recommended 'Birth Cohort Screening' of the U.S. Adult population to reduce the future burden of undiagnosed HCV infections in the U.S. Our aim was to assess independent predictors of receiving treatment in a cohort of HCV-infected patients. The Hepatitis C follow-up questionnaires of the National Health and Nutrition Examination Surveys (NHANES) conducted from 2001 to 2010 were used. The NHANES participants who tested positive for HCV RNA were followed by CDC 6 months after initial testing with questions related to their awareness of their infection and history or intention to receive treatment. A total of 500 NHANES participants tested positive for HCV RNA and were targeted for follow-up. Of these, only 203 had completed the follow-up questionnaire (response rate of 40.6%). Of these, only 101 (50%) knew about their HCV positivity before NHANES, and from them, only 34 (17%) had received treatment. In multivariate analysis, prior knowledge about their HCV infection in HCV-positive individuals was independently associated with receiving routine care from a doctor or HMO, with higher income, female gender, being in poor or fair health and not consuming excessive amounts of alcohol. On the other hand, the knowledge about HCV infection was the only independent predictor of receiving anti-HCV treatment (odds ratio 6.14). Knowledge about having HCV infection is the only independent predictor of receiving treatment. Therefore, birth cohort screening of the U.S. General population could lead to wider identification of HCV and potentially better management of the future burden of HCV and its complications.

Introduction

Chronic hepatitis C is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma with tremendous economic burden.[1–6] Over the past two decades, anti-HCV treatment regimens with better efficacy and shorter duration of treatment have been developed.[7–15] Despite the increasingly better treatment regimens, it is estimated that the 2.4 million Americans with HCV remain unaware of their HCV status and are undiagnosed [16]. This issue has led to the recent recommendations to screen the Baby Boomers born between 1945 and 1965.[17–19] Although this new screening strategy is expected to increase the identification of HCV-infected patients, a number of barriers to treatment remain.[20–27] The aim of this study was to assess the follow-up of patients diagnosed with HCV during NHANES screening and identify factors that potentially led to HCV treatment.

Methods

Study Population

In this study, five continuous cycles of National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2010 were used. In these NHANES cycles, in addition to extensive demographic, clinical and laboratory data, a follow-up hepatitis C questionnaire was submitted to eligible participants. Hepatitis C was diagnosed with an HCV-enzyme-linked immunosorbent assay with positive tests confirmed with HCV-RNA testing.[28, 29]

As a part of NHANES, all HCV patients received a Report of Findings letter informing them of their HCV test result and encouraging them to seek medical follow-up. Six months after examination, a number of attempts to administer a Hepatitis C Follow-Up telephone questionnaire.[30]

The NHANES participants were also asked about the history and primary source of receiving healthcare and were requested to evaluate their general health status on the scale from excellent to poor (all included into the Hospital Utilization and Access to Care questionnaire). The type of health insurance coverage the participants reported having at the time of examination was collected from the Health Insurance questionnaire. The presence of depression was ascertained using the PHQ-9 questionnaire.[31]

Statistical Analysis

Pairwise comparisons were made using chi-square or, in case of a sample of five or less subjects, Fisher's exact test for binary parameters (such as presence vs. absence of a condition) and nonparametric Mann–Whitney test for continuous parameters (such as AST). To identify clinical and socio-demographic factors that could be independently associated with being aware of HCV infection and having received anti-HCV treatment, we selected the parameters that returned a statistically significant difference after pairwise comparison and included them into a logistic regression. The level of statistical significance was set at P-value of 0.05 or less. As recommended by NHANES, the described population was used only for a cross-sectional study, and all reported percentages are not population estimates but the percentages of the respondents in the study cohort. The analysis was run using SAS 9.1 (SAS Institute, Cary, NC, USA). The study was considered exempt by the Inova Institutional Review Board.

Results

From the NHANES cohort screened between 2001 and 2010, 500 were anti-HCV positive and, thus, were sent a respective letter. The Hepatitis C Follow-Up questionnaire was completed by 203 (response rate of 40.6%). The major reason for the absence of follow-up was unavailability of a participant for a contact (80–95%). However, the proportion of those who were successfully contacted and refused to participate in the follow-up increased from 3.2% in 2001–2002 to 24.0% in 2009–2010, and these findings were consistent with a previous report.[32]

Of those who completed the Hepatitis C Follow-Up questionnaire, 101 (49.8%) reported that they were aware of their infection before receiving the letter from NHANES. Compared with those who found out about their HCV status for the first time, these individuals had higher income and were more likely to be non-Mexican Hispanic, female, college-educated and married (). They were also less likely to report excessive alcohol consumption, more likely to be insured, by a private insurance provider in particular, more likely to see a doctor or HMO for healthcare and less likely to report good to excellent health ().

Table 1.  Comparison of individuals who were and were not aware of their HCV infection before being tested for NHANES

  Knew before NHANES Did not know before NHANES P
n 101 102 <0.0001
   Proportion, % 49.75 50.25  
   Received treatment, % 28 (27.7) 6 (5.9)  
Demographics
   Age, years 51.4 ± 10.2 48.75 ± 13.6 0.1744
   Male, % 57 (56.4) 74 (72.5) 0.0164
   White, % 47 (46.5) 48 (47.1) 0.9403
   Black, % 25 (24.8) 32 (31.4) 0.2940
   Mexican American, % 15 (14.9) 17 (16.7) 0.7227
   Other hispanic, % 10 (9.9) 2 (2.0) 0.0164
   Were in military service, % 23 (23.0) 21 (21.0) 0.7328
   Have college degree, % 10 (10.0) 2 (2.0) 0.0189
   Married, % 47 (46.5) 31 (31.0) 0.0238
   Income-to-poverty ratio 2.17 ± 1.52 1.73 ± 1.39 0.0360
Social history
   Excessive alcohol consumption, % 5 (7.9) 26 (36.6) <0.0001
   Smoking, % 49 (76.6) 55 (78.6) 0.7805
   Injected drug history, % 44 (51.2) 36 (45.0) 0.4272
Health insurance
   Insured, % 86 (86.9) 61 (60.4) <0.0001
   Private insurance, % 49 (49.5) 29 (29.0) 0.0031
   Medicare/Medicaid, % 34 (34.3) 26 (26.0) 0.1997
   Government-sponsored insurance, % 14 (14.1) 12 (12.0) 0.6540
Healthcare access
   Source of healthcare: clinic or health centre, % 19 (18.8) 23 (22.5) 0.5110
   Doctor's office or HMO, % 66 (65.3) 39 (38.2) 0.0001
   Hospital ER, % 4 (4.0) 6 (5.9) 0.5270
   Hospital outpatient department, % 7 (6.9) 7 (6.9) 0.9848
   Was in hospital overnight (last year), % 20 (19.8) 13 (12.7) 0.1730
   Saw a mental health specialist (last year), % 20 (19.8) 11 (10.8) 0.0741
General health
   Self-reported health: fair or poor, % 49 (48.5) 28 (27.5)  
   Good to excellent, % 52 (51.5) 74 (72.5) 0.0020
   ALT, SI 48.7 ± 37.0 55.9 ± 45.4 0.2396
   AST, SI 47.3 ± 34.5 54.7 ± 46.3 0.3289

In multivariate analysis, male gender (OR: 0.302 [0.126–0.725]), excessive alcohol consumption (OR: 0.207 [0.068–0.636]) and being in good to excellent health (OR: 0.368 [0.149–0.912]) were all independently associated with the lack of knowledge about being infected with HCV. On the other hand, seeing a doctor or HMO rather than a clinic or a hospital ER or outpatient department (OR: 2.481 [1.087–5.662]) and having higher income-to-poverty ratio (OR: 1.447 [1.077–1.944]) were associated with being aware of the HCV-positive status.

Of the study cohort, 34 individuals (16.7%) reported receiving treatment, whilst 44 (21.7%) reported not having seen a doctor and 107 (52.7%) were not recommended by a healthcare provider to do anything about the infection. The reasons for not receiving treatment are listed in . Those who were recommended and chose to get treated were more likely to be college-educated and more likely to report suboptimal (fair or poor) health ().

Table 2.  Comparison of those who did and did not receive treatment for HCV infection

  Treated Not treated P
n 34 169  
   Proportion, % 16.75 83.25  
Demographics
   Age, years 52.2 ± 9.2 49.6 ± 12.5 0.2226
   Male, % 20 (58.8) 111 (65.7) 0.4457
   White, % 18 (52.9) 77 (45.6) 0.4314
   Black, % 8 (23.5) 49 (29.0) 0.5176
   Mexican American, % 5 (14.7) 27 (16.0%) 0.8528
   Other hispanic, % 2 (5.9) 10 (5.9) 0.9937
   Were in military service, % 10 (29.4) 34 (20.5) 0.2521
   Have college degree, % 5 (14.7) 7 (4.3) 0.0202
   Married, % 17 (50.0) 61 (36.5) 0.1417
   Income-to-poverty ratio 2.25 ± 1.57 1.89 ± 1.45 0.1400
Social history
   Excessive alcohol consumption, % 2 (10.5) 29 (25.2) 0.1594
   Smoking, % 16 (76.2) 88 (77.9) 0.8648
   Injected drug history, % 16 (51.6) 64 (47.4) 0.6725
Health insurance
   Insured, % 29 (85.3) 118 (71.1) 0.0871
   Private insurance, % 17 (50.0) 61 (37.0) 0.1564
   Medicare/Medicaid, % 8 (23.5) 52 (31.5) 0.3555
   Government-sponsored insurance, % 6 (17.6) 20 (12.1) 0.3839
General health
   Self-reported health: fair or poor, % 16 (47.1) 110 (65.1)  
   Good to excellent, % 18 (52.9) 59 (34.9) 0.0480
   ALT, SI 61.5 ± 50.6 50.4 ± 39.3 0.6281
   AST, SI 59.0 ± 47.0 49.4 ± 39.5 0.4243
Chronic conditions
   Arthritis, % 15 (44.1) 62 (37.8) 0.4919
   Asthma, % 6 (17.6) 25 (14.8) 0.6729
   Cancer, % 4 (11.8) 15 (9.1%) 0.6370
   Chronic hepatitis B, % 0 (0.0) 0 (0.0) NA
   COPD, % 5 (15.2) 21 (13.5) 0.7979
   Congestive heart failure, % 0 (0.0) 16 (9.8) 0.0574
   Depression, % 1 (4.0) 4 (5.8) 0.7315
   Severe depression, % 1 (4.0) 1 (1.4) 0.4489
   Diabetes, % 6 (17.6) 20 (11.8) 0.3547
   HIV, % 0 (0.0) 3 (1.9) 0.4239
   Ischaemic heart disease, % 1 (2.9%) 19 (11.6) 0.1279
   Kidney failure, % 1 (2.9) 15 (9.1) 0.2269
   Obesity, % 12 (35.3) 33 (20.8) 0.0687
   Stroke, % 1 (2.9) 9 (5.5) 0.5371
HCV infection management
   Aware of HCV infection before NHANES, % 28 (82.4) 73 (43.2) <0.0001
   Had liver biopsy, % 28 (82.4) 16 (9.5) <0.0001
Reason for not receiving treatment
   Did not go to doctor, % NA 44 (26.0) NA
   Doctor did not recommend treatment, % NA 105 (62.1) NA
   Fear of side effects, % NA 10 (5.9) NA
   Treatment must be self-injected,% NA 5 (3.0) NA
   Treatment cost, % NA 13 (7.7) NA
   Expect better treatment, % NA 4 (2.4) NA
   Other reason, % NA 17 (10.1) NA

NA, not applicable.

The percentages do not add up to 100% because a participant might have chosen more than one reason.

Finally, there was a significant association between awareness of being infected with HCV and history of treatment: 82.4% of those who received anti-HCV treatment were aware of their infection before being tested for NHANES. In contrast to those who did not receive any treatment, regardless of a reason, only 43.2% knew they were infected. On the other hand, of those who were aware of their infection before receiving a letter from NHANES, 27.7% reported having been treated, whilst of those who did not know about their HCV before NHANES, only 5.9% reported any anti-HCV treatment (P < 0.0001).

In multivariate analysis, prior knowledge about being infected with HCV was the only variable which was independently associated with having received treatment: OR (95% CI) = 6.137 (2.415–15.598), P = 0.0001.

Discussion

This study assesses the follow-up of patients who were identified as having hepatitis C during NHANES screening surveys. Our data suggest that a number of clinical and demographic factors are associated with lack of treatment for hepatitis C. However, after controlling for confounders by multivariate analysis, only previous knowledge of HCV was independently associated with treatment. This data highlight the importance of screening for HCV that could lead to increased knowledge about HCV and potentially result in higher likelihood of receiving appropriate treatment.

Our data also suggest that being male, feeling in excellent health and excessive alcohol consumption are independently associated with lack of knowledge about HCV infection. Again, this is an important finding that highlights the importance of screening in individuals with CH-C who are especially at risk of progressive liver disease and mortality, that is, individuals with HCV infection who excessively drink alcohol. Our data also indicate that access to care and higher income are independent factors associated with awareness of HCV infection and therefore receiving appropriate care. This conundrum highlights the dilemma of HCV infection. The population with the highest prevalence of HCV and the greatest need for appropriate treatment also belong to the lower socioeconomic group with more limited access to care and less likely to become aware of their HCV status. This dilemma should be addressed by health policy makers to widely implement the 'birth cohort' screening strategies for HCV. Additionally, access to appropriate care, including advice against alcohol consumption and anti-viral treatment, must be provided. Without a comprehensive policy to deal with the burden of CH-C, the toll on health, health-related quality of life and the socioeconomic burden of HCV will continue to rise.

The limitation of our study is the lack of direct patient data in the follow-up. Additionally, the relatively small sample size and a short follow-up may have resulted in our inability to show some important association. Nevertheless, the design of the study includes the use of an established database, although, given the low response rate, we could not make population-wide conclusions.

In summary, our data suggest that HCV knowledge of infection is the most important predictor of receiving treatment. This data provide additional support for the recently recommended screening of U.S. Population based on birth cohort.

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Abbreviations
CDC, center for disease control; CHC, chronic hepatitis C; NHANES, national health and nutrition examination survey.

J Viral Hepat. 2013;20(8):550-555. © 2013  Blackwell Publishing

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