## Abstract

Background. The Chronic Hepatitis Cohort Study (CHeCS), a dynamic prospective, longitudinal, observational cohort study, was created to assess the clinical impact of chronic viral hepatitis in the United States. This report describes the cohort selection process, baseline demographics, and insurance, biopsy, hospitalization, and mortality rates.

Methods. Electronic health records of >1.6 million adult patients seen from January 2006 through December 2010 at 4 integrated healthcare systems in Detroit, Michigan; Danville, Pennsylvania; Portland, Oregon; and Honolulu, Hawaii were collected and analyzed.

Results. Of 2202 patients with chronic hepatitis B virus (HBV) infection, 50% were aged 44–63 years, 57% male, 58% Asian/Pacific Islander, and 13% black; and 5.1% had Medicaid, 16.5% Medicare, and 76.3% private insurance. During 2001–2010, 22.3% had a liver biopsy and 37.9% were hospitalized. For the 8810 patients with chronic hepatitis C virus (HCV) infection, 75% were aged 44–63 years, 60% male, 23% black; and 12% had Medicaid, 23% Medicare, and 62% private insurance. During 2001–2010, 38.4% had a liver biopsy and 44.3% were hospitalized. Among persons in care, 9% of persons with HBV and 14% of persons with HCV infection, mainly those born during 1945–1964, died during the 2006–2010 five-year period.

Conclusions. Baseline demographic, hospitalization, and mortality data from CHeCS highlight the substantial US health burden from chronic viral hepatitis, particularly among persons born during 1945–1964.

In the United States, an estimated 3.2 million persons have chronic hepatitis C virus (HCV) infection and another 1.0 million have chronic hepatitis B virus (HBV) infection [1–3]. However, chronic viral hepatitis is not widely recognized as a serious public health problem. As a result, viral hepatitis prevention, control, and surveillance programs have not been adequately resourced [4]; it has been dubbed the “silent epidemic” by Dr Howard Koh, the current US Assistant Secretary of Health [5]. To assess the larger implications and impact of chronic hepatitis B and C on the US population, we designed the Chronic Hepatitis Cohort Study (CHeCS).

The study is being carried out during a period of rapid development of viral hepatitis treatment alternatives and evolution in the healthcare system, and there are many important reasons for such an effort. For purposes of treatment and care, clinicians and others need current information on the spectrum of disease and characteristics of persons in care; types of therapies in use and their evolving benefits, risks, and adverse effects; and other factors influencing outcomes. From the larger public health and policy perspective, there is an ongoing need for information about the health burden and costs of care and mortality, implementation and effectiveness of recommended screening and care practices, access and barriers to care and treatment (who is in care and who is receiving therapy), and the costs and potential savings of appropriate care and treatment. Such information is not available from controlled clinical trials or interventional studies that, while essential for determining optimal therapy for hepatitis B and C, are limited by expense, short duration, and small numbers.

CHeCS, a “dynamic” multicenter cohort study—with rolling admissions and follow-up from patients’ regular visits to their clinicians—was designed along principles used for a large Centers for Disease Control and Prevention (CDC)–funded study of HIV infection, the HIV Outpatient Study [6]. The purpose of this analysis is to describe the cohort selection process and baseline patient population characteristics.

## METHODS

The initial cohort was created based on electronic medical and billing electronic health records (EHRs) of patients aged ≥18 years who had a service provided during 2006–2008 at 1 of 4 sites: Geisinger Health System, Danville, Pennsylvania; Henry Ford Health System, Detroit, Michigan (coordinating center); Kaiser Permanente Northwest, Portland, Oregon; and Kaiser Permanente, Honolulu, Hawaii. EHRs and billing data were collected for each patient from their first system encounter through 2010 and supplemented with individual chart review, and included patient demographics, medical encounters, laboratory results, diagnoses, and procedures including liver biopsy. Electronic data used in this analysis were available retrospectively through 1997 at the Detroit and Portland sites, through 1998 from the Hawaii site, and through 2001 from the Danville site. Analyses for the tables were limited to the years (2001–2010) for which complete data were currently available. Household income data were estimated from census tract data using geocoded addresses.

The study protocol was reviewed by an institutional review board approved by the federal Office for Human Research Protections at each participating site.

### Cohort Selection

Algorithms for inclusion in the chronic hepatitis B and C cohorts were developed and applied to the EHR and administrative data of patients aged ≥18 years from all sites with any healthcare utilization during 2006–2008. The complex algorithms were developed with a bias to capture the greatest number of verifiable chronic hepatitis B and C cases from the raw observational data, while excluding those with a single unconfirmed diagnosis or laboratory evidence that might be due to acute disease, error, or lack of necessary clinical or laboratory workup. Complete observation time for each patient was determined to be time from first evidence of hepatitis infection in the EHR, including retrospective data prior to 2006, until last health system encounter, death, or 31 December 2010.

Electronic data from 2006–2008 were reviewed to determine enrollment candidacy, and data from candidate patients were reviewed from their earliest health system encounter through 2008 to determine cohort eligibility. Patients were included in the chronic hepatitis B and C cohorts based on fulfillment of a combination of laboratory-based and International Classification of Diseases, Ninth Revision (ICD-9)–based criteria (Figures 1 and 2). In brief, for inclusion in the hepatitis B cohort, patients had to fulfill at least 2 criteria (ie, 2 positive laboratory tests consistent with current HBV infection [positive for HBV surface antigen, e-antigen, or DNA test]), or a positive laboratory test and an ICD-9 diagnosis code, or 2 ICD-9 diagnosis codes obtained at least 6 months apart (Figure 1). Patients in all phases of chronic HBV infection (immune-tolerant, immune-active, and inactive or “immune carrier”) were included. For the hepatitis C cohort, a similar approach was used: patients were included who had a positive hepatitis C RNA test, or ICD-9 diagnosis codes indicative of hepatitis C infection (Figure 2) at least 6 months apart from each other or from a positive hepatitis C antibody test or alanine aminotransferase elevation.

Figure 1.

Hepatitis B cohort inclusion criteria. 1Qualifying chronic hepatitis B International Classification of Diseases, Ninth Revision (ICD-9) codes: 070.22, 070.23, 070.32, 070.33; acute/unspecified hepatitis B ICD-9 codes: 070.20, 070.21, 070.30, 070.31. 2Qualifying lab tests: hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B virus (HBV) DNA. 3Laboratory-based inclusion categories: category 1 (n = 1853), a viral hepatitis B or chronic liver disease ICD-9 diagnosis (571.5 cirrhosis of liver without mention of alcohol, 456.0–456.1 esophageal varices, 789.59 other ascites, 155.0 liver cancer, V42.7 liver replaced by transplant, V49.83 awaiting organ transplant status) plus positive laboratory evidence of HBsAg or HBV DNA; category 2 (n = 1188), ≥2 positive laboratory results for HBsAg, HBeAg, or HBV DNA, occurring at least 6 months apart; category 3 (n = 529), a negative hepatitis B immunoglobulin M core antibody (IgM anti-HBc) lab result concurrent or prior to a positive HBsAg or HBV DNA; category 4 (n = 1180), a positive hepatitis B core antibody (anti-HBc) and positive HBsAg; category 5 (n = 838), a positive HBsAg and an elevated alanine aminotransferase occurring at least 6 months apart. 4ICD-9 inclusion criterion: ≥2 ICD-9 diagnoses indicative of viral hepatitis B1 at least 6 months apart, in the absence of a positive HBsAg or HBV DNA. Abbreviations: HBV, hepatitis B virus; ICD-9, International Classification of Diseases, Ninth Revision.

Figure 1.

Hepatitis B cohort inclusion criteria. 1Qualifying chronic hepatitis B International Classification of Diseases, Ninth Revision (ICD-9) codes: 070.22, 070.23, 070.32, 070.33; acute/unspecified hepatitis B ICD-9 codes: 070.20, 070.21, 070.30, 070.31. 2Qualifying lab tests: hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B virus (HBV) DNA. 3Laboratory-based inclusion categories: category 1 (n = 1853), a viral hepatitis B or chronic liver disease ICD-9 diagnosis (571.5 cirrhosis of liver without mention of alcohol, 456.0–456.1 esophageal varices, 789.59 other ascites, 155.0 liver cancer, V42.7 liver replaced by transplant, V49.83 awaiting organ transplant status) plus positive laboratory evidence of HBsAg or HBV DNA; category 2 (n = 1188), ≥2 positive laboratory results for HBsAg, HBeAg, or HBV DNA, occurring at least 6 months apart; category 3 (n = 529), a negative hepatitis B immunoglobulin M core antibody (IgM anti-HBc) lab result concurrent or prior to a positive HBsAg or HBV DNA; category 4 (n = 1180), a positive hepatitis B core antibody (anti-HBc) and positive HBsAg; category 5 (n = 838), a positive HBsAg and an elevated alanine aminotransferase occurring at least 6 months apart. 4ICD-9 inclusion criterion: ≥2 ICD-9 diagnoses indicative of viral hepatitis B1 at least 6 months apart, in the absence of a positive HBsAg or HBV DNA. Abbreviations: HBV, hepatitis B virus; ICD-9, International Classification of Diseases, Ninth Revision.

Figure 2.

Hepatitis C cohort inclusion criteria. 1Qualifying chronic hepatitis C International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes: 070.44, 070.54, 070.70, 070.71; acute/unspecified hepatitis C ICD-9 codes: 070.41, 070.51. 2Qualifying lab tests were a positive or detectable hepatitis C virus antibody (anti-HCV) test, and/or HCV RNA test, and/or hepatitis C genotype test. 3ICD-9–based categories: category 1 (n = 3506): ≥2 ICD-9 diagnoses indicating viral hepatitis C1, separated by at least 6 months at any time during the patient's medical history; category 2 (n = 2877), a viral hepatitis C1 or qualifying chronic liver disease ICD-9 diagnosis (571.5 cirrhosis of liver without mention of alcohol, 456.0–456.1 esophageal varices, 789.59 other ascites, 155.0 liver cancer, V42.7 liver replaced by transplant, V49.83 awaiting organ transplant status) separated at least 6 months apart from a positive anti-HCV test. Abbreviations: HCV, hepatitis C virus; ICD-9, International Classification of Diseases, Ninth Revision.

Figure 2.

Hepatitis C cohort inclusion criteria. 1Qualifying chronic hepatitis C International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes: 070.44, 070.54, 070.70, 070.71; acute/unspecified hepatitis C ICD-9 codes: 070.41, 070.51. 2Qualifying lab tests were a positive or detectable hepatitis C virus antibody (anti-HCV) test, and/or HCV RNA test, and/or hepatitis C genotype test. 3ICD-9–based categories: category 1 (n = 3506): ≥2 ICD-9 diagnoses indicating viral hepatitis C1, separated by at least 6 months at any time during the patient's medical history; category 2 (n = 2877), a viral hepatitis C1 or qualifying chronic liver disease ICD-9 diagnosis (571.5 cirrhosis of liver without mention of alcohol, 456.0–456.1 esophageal varices, 789.59 other ascites, 155.0 liver cancer, V42.7 liver replaced by transplant, V49.83 awaiting organ transplant status) separated at least 6 months apart from a positive anti-HCV test. Abbreviations: HCV, hepatitis C virus; ICD-9, International Classification of Diseases, Ninth Revision.

Trained medical abstractors reviewed the EHRs of patients identified as eligible from first system encounter through 2010 to collect liver biopsy results, outside system laboratory results, and detailed antiviral therapy data during 2006–2010 as well as summary history of antiviral therapy prior to 2006, and to confirm chronic infection status. Abstractors flagged charts lacking documentation that a liver specialist had diagnosed chronic hepatitis B or C, or with documentation that the patient had been diagnosed with acute hepatitis or had chronic hepatitis ruled out. Flagged charts were reviewed under the supervision of a hepatitis clinician using hepatologist-developed criteria. Cases for which chronic infection had been ruled out were excluded from the cohort. Some cases were determined to have insufficient follow-up to confirm chronic hepatitis infection status. To assess the validity of our electronic inclusion criteria, we analyzed exclusion rates among the ICD-9–based inclusion criteria and laboratory-based criteria.

### Mortality

Deaths from all causes among cohort patients that occurred or were reported to the health system facilities during 2006–2010 were enumerated. Each health system compared records to the Social Security Death Index or National Death Index to enhance ascertainment. As patients were selected for cohort eligibility based on health system service encounters during 2006–2008, the start of observation for death rate calculation was the later of 1 January 2006 or first hepatitis diagnosis date. Observation time was truncated at 31 December 2010 or date of death, whichever was earlier. All-cause death rates were calculated and for HCV compared with published National Health and Nutrition Examination Survey (NHANES) III data on patients with and without chronic HCV infection [7].

## RESULTS

### Chronic Hepatitis B Cohort

We examined the records of 1 652 055 patients aged ≥18 years in the 4 participating health systems who had 1 or more services provided during 2006–2008, and a total of 2535 met the electronic hepatitis B cohort inclusion criteria (Figure 1). After exclusion of patients for whom chronic infection was not confirmed by abstractor records review, 2202 (87%) remained in the cohort (Figure 1). Median observation time was 5.3 years (range, <1 to 16 years), with a total of 14 034 person-years of observation.

Demographic and clinical features of the 2202 confirmed chronic hepatitis B cohort patients are shown in Table 1. About half (47.9%) were born between 1945 and 1964, and an additional 22.8% were born between 1965 and 1974. Racial mix varied by study site, ranging from 21.9% Asian/Pacific Islander in Danville to 95.0% in Hawaii, and from 1% black in Hawaii to 36% in Detroit. Household income (estimated from census tract geocode) was less than $30 000/year for 13.6% of patients overall, ranging from 7.7% in Portland to 31.2% in Danville. Overall insurance coverage included 5.1% with Medicaid, 16.5% Medicare, and 76.3% private insurance, but payer mix varied by site. The percentage of patients having only public insurance (Medicaid or Medicare) ranged from 1.7% in Portland to 27.5% in Danville; 11.4% of patients in Danville and 4.0% in Detroit were uninsured. Table 1. Demographic, Clinical, and Laboratory Characteristics of Patients With Chronic Hepatitis B Characteristic Total (N = 2202) Portland, Oregon (n = 776; 35.2%) Hawaii (n = 653; 29.7%) Detroit, Michigan (n = 606; 27.5%) Danville, Pennsylvania (n = 167; 7.6%) Demographic Characteristic Birth year cohort (age in 2008) 1985–1990 (18–23 y) 54 (2.5%) 19 (2.4%) 20 (3.1%) 10 (1.7%) 5 (3.0%) 1975–1984 (24–33 y) 338 (15.3%) 128 (16.5%) 114 (17.5%) 62 (10.2%) 34 (20.4%) 1965–1974 (34–43 y) 501 (22.8%) 192 (24.7%) 130 (19.9%) 147 (24.3%) 32 (19.2%) 1955–1964 (44–53 y) 602 (27.3%) 215 (27.7%) 159 (24.3%) 183 (30.2%) 45 (26.9%) 1945–1954 (54–63 y) 452 (20.5%) 148 (19.1%) 132 (20.2%) 139 (22.9%) 33 (19.8%) 1935–1944 (64–73 y) 177 (8.0%) 55 (7.1%) 68 (10.4%) 47 (7.8%) 7 (4.2%) ≤1934 (≥74 y) 78 (3.5%) 19 (2.4%) 30 (4.6%) 18 (3.0%) 11 (6.6%) Sex Female 954 (43.3%) 338 (43.6%) 331 (50.7%) 223 (36.8%) 62 (37.1%) Male 1248 (56.7%) 438 (56.4%) 322 (49.3%) 383 (63.2%) 105 (62.9%) Race/ethnicity Race status known 1803 (81.9%) 584 (75.3%) 518 (79.3%) 546 (90.1%) 155 (92.8%) White 510 (28.3%) 198 (33.9%) 18 (3.5%) 187 (34.2%) 107 (69.0%) Black 239 (13.3%) 23 (3.9%) 5 (1.0%) 197 (36.1%) 14 (9.0%) Asian 843 (46.8%) 345 (59.1%) 309 (59.7%) 155 (28.4%) 34 (21.9%) Pacific Islander 198 (11.0%) 15 (2.6%) 183 (35.3%) American Indian/Alaska Native 13 (0.7%) 3 (0.5%) 3 (0.6%) 7 (1.3%) Ethnicity status known 1706 (77.5%) 493 (63.5%) 480 (73.5%) 566 (93.4%) 167 (100.0%) Hispanic ethnicity 39 (2.3%) 10 (2.0%) 11 (2.3%) 6 (1.1%) 12 (7.2%) Estimated household income (census tract geocode) Status known 2132 (96.8%) 767 (98.8%) 633 (96.9%) 575 (94.9%) 157 (94.0%) <$15 000 33 (1.5%) 4 (0.5%) 4 (0.6%) 17 (3.0%) 8 (5.1%)
$15 000–$29 000 258 (12.1%) 55 (7.2%) 63 (10.0%) 99 (17.2%) 41 (26.1%)
$30 000–$49 000 904 (42.4%) 370 (48.2%) 263 (41.5%) 180 (31.3%) 91 (58.0%)
$50 000–$75 000 674 (31.6%) 260 (33.9%) 248 (39.2%) 150 (26.1%) 16 (10.2%)
>$75 000 263 (12.3%) 78 (10.2%) 55 (8.7%) 129 (22.4%) 1 (0.6%) Insurance Status known 2096 (95.2%) 698 (89.9%) 625 (95.7%) 606 (100.0%) 167 (100.0%) Medicaid 107 (5.1%) 12 (1.7%) 36 (5.8%) 36 (5.9%) 23 (13.8%) Medicare only 23 (1.1%) 23 (13.8%) Medicare Plus 323 (15.4%) 70 (10.0%) 90 (14.4%) 163 (26.9%) Private 1600 (76.3%) 616 (88.3%) 499 (79.8%) 383 (63.2%) 102 (61.1%) None 43 (2.1%) 24 (4.0%) 19 (11.4%) Clinical or Laboratory Characteristic ALT Ever measured during 2001-2010a 2173 (98.7%) 768 (99.0%) 644 (98.6%) 595 (98.2%) 166 (99.4%) Highest ever ALT in 2001–2010a Less than ULN 1103 (50.8%) 401 (52.2%) 397 (61.6%) 237 (39.8%) 68 (41.0%) >ULN to ≤2 × ULN 457 (21.0%) 171 (22.3%) 123 (19.1%) 128 (21.5%) 35 (21.1%) >2 × ULN 613 (28.2%) 196 (25.5%) 124 (19.3%) 230 (38.7%) 63 (38.0%) Most recent ALT in 2001–2010a Less than ULN 1802 (82.9%) 624 (81.3%) 572 (88.8%) 485 (81.5%) 121 (72.9%) >ULN to ≤2 × ULN 253 (11.6%) 103 (13.4%) 53 (8.2%) 68 (11.4%) 29 (17.5%) >2 × ULN 118 (5.4%) 41 (5.3%) 19 (3.0%) 42 (7.1%) 16 (9.6%) HBV RNA Ever measured during 2001-2010a 1510 (68.6%) 449 (57.9%) 464 (71.1%) 505 (83.3%) 92 (55.1%) Most recent viral load during2001–2010a,b, IU/mL Undetectable 706 (46.8%) 148 (33.0%) 224 (48.3%) 283 (56.0%) 51 (55.4%) >300 to ≤2000 (detectable) 274 (18.1%) 100 (22.3%) 101 (21.8%) 62 (12.3%) 11 (12.0%) >2000 to ≤20 000 209 (13.8%) 76 (16.9%) 66 (14.2%) 66 (13.1%) 1 (1.1%) >20 000 301 (19.9%) 125 (27.8%) 73 (15.7%) 94 (18.6%) 9 (9.8%) E-antigen Ever tested during 2001–2010a,c 1471 (66.8%) 492 (63.4%) 448 (68.6%) 422 (69.6%) 109 (65.3%) Ever e-antigen positive 431 (29.3%) 145 (29.5%) 101 (22.5%) 143 (33.9%) 42 (38.5%) Always e-antigen negative 1035 (70.4%) 345 (70.1%) 346 (77.2%) 277 (65.6%) 67 (61.5%) Most recent e-antigen positive 338 (23.0%) 118 (24.0%) 82 (18.3%) 108 (25.6%) 30 (27.5%) Most recent e-antigen negative 1128 (76.7%) 371 (75.4%) 364 (81.3%) 314 (74.4%) 79 (72.5%) Liver biopsy at least once during 2001–2010a 490 (22.3%) 151 (19.5%) 130 (19.9%) 169 (27.9%) 40 (24.0%) HIV coinfected 142 (6.4%) 54 (7.0%) 17 (2.6%) 60 (9.9%) 11 (6.6%) Ever tested for HIVa 697 (31.7%) 229 (29.5%) 221 (33.8%) 234 (38.6%) 13 (7.8%) Hospitalized Ever hospitalized during 2001–2010 835 (37.9%) 299 (38.5%) 266 (40.7%) 210 (34.7%) 60 (35.9%) Ever had liver transplant, through 2010a 46 (2.1%) 6 (0.8%) 5 (0.8%) 32 (5.3%) 3 (1.8%) Deaths, 2006–2010 Died 2006–2010 199 (9.0%) 38 (4.9%) 54 (8.3%) 83 (13.7%) 24 (14.4%) Death rate per 1000 py (95% CI) 21.6 (15.5 – 27.7) 11.2 (3.8 – 18.7) 19.9 (9.2 – 30.7) 32.6 (18.5 – 46.7) 41.5 (11.3 – 71.8) No. of deaths by birth year cohort (years of age in 2008) and death rate per 1000 py (95% CI) 1985–1990 (18–23 y) 1975–1984 (24–33 y) 3 (0.9%) Death rate 2.2 (0–7.1) 1965–1974 (34–43 y) 22 (4.4%) Death rate 10.2 (1.4–19.1) 1955–1964 (44–53 y) 44 (7.3%) Death rate 17.0 (6.7–27.3) 1945–1954 (54–63 y) 69 (15.3%) Death rate 37.1 (19.7–54.5) 1935–1944 (64–73 y) 33 (18.6%) Death rate 46.5 (15.4–77.5) ≤1934 (≥74 y) 28 (35.9%) Death rate 99.7 (33.2–166.1) Characteristic Total (N = 2202) Portland, Oregon (n = 776; 35.2%) Hawaii (n = 653; 29.7%) Detroit, Michigan (n = 606; 27.5%) Danville, Pennsylvania (n = 167; 7.6%) Demographic Characteristic Birth year cohort (age in 2008) 1985–1990 (18–23 y) 54 (2.5%) 19 (2.4%) 20 (3.1%) 10 (1.7%) 5 (3.0%) 1975–1984 (24–33 y) 338 (15.3%) 128 (16.5%) 114 (17.5%) 62 (10.2%) 34 (20.4%) 1965–1974 (34–43 y) 501 (22.8%) 192 (24.7%) 130 (19.9%) 147 (24.3%) 32 (19.2%) 1955–1964 (44–53 y) 602 (27.3%) 215 (27.7%) 159 (24.3%) 183 (30.2%) 45 (26.9%) 1945–1954 (54–63 y) 452 (20.5%) 148 (19.1%) 132 (20.2%) 139 (22.9%) 33 (19.8%) 1935–1944 (64–73 y) 177 (8.0%) 55 (7.1%) 68 (10.4%) 47 (7.8%) 7 (4.2%) ≤1934 (≥74 y) 78 (3.5%) 19 (2.4%) 30 (4.6%) 18 (3.0%) 11 (6.6%) Sex Female 954 (43.3%) 338 (43.6%) 331 (50.7%) 223 (36.8%) 62 (37.1%) Male 1248 (56.7%) 438 (56.4%) 322 (49.3%) 383 (63.2%) 105 (62.9%) Race/ethnicity Race status known 1803 (81.9%) 584 (75.3%) 518 (79.3%) 546 (90.1%) 155 (92.8%) White 510 (28.3%) 198 (33.9%) 18 (3.5%) 187 (34.2%) 107 (69.0%) Black 239 (13.3%) 23 (3.9%) 5 (1.0%) 197 (36.1%) 14 (9.0%) Asian 843 (46.8%) 345 (59.1%) 309 (59.7%) 155 (28.4%) 34 (21.9%) Pacific Islander 198 (11.0%) 15 (2.6%) 183 (35.3%) American Indian/Alaska Native 13 (0.7%) 3 (0.5%) 3 (0.6%) 7 (1.3%) Ethnicity status known 1706 (77.5%) 493 (63.5%) 480 (73.5%) 566 (93.4%) 167 (100.0%) Hispanic ethnicity 39 (2.3%) 10 (2.0%) 11 (2.3%) 6 (1.1%) 12 (7.2%) Estimated household income (census tract geocode) Status known 2132 (96.8%) 767 (98.8%) 633 (96.9%) 575 (94.9%) 157 (94.0%) <$15 000 33 (1.5%) 4 (0.5%) 4 (0.6%) 17 (3.0%) 8 (5.1%)
$15 000–$29 000 258 (12.1%) 55 (7.2%) 63 (10.0%) 99 (17.2%) 41 (26.1%)
$30 000–$49 000 904 (42.4%) 370 (48.2%) 263 (41.5%) 180 (31.3%) 91 (58.0%)
$50 000–$75 000 674 (31.6%) 260 (33.9%) 248 (39.2%) 150 (26.1%) 16 (10.2%)
>$75 000 263 (12.3%) 78 (10.2%) 55 (8.7%) 129 (22.4%) 1 (0.6%) Insurance Status known 2096 (95.2%) 698 (89.9%) 625 (95.7%) 606 (100.0%) 167 (100.0%) Medicaid 107 (5.1%) 12 (1.7%) 36 (5.8%) 36 (5.9%) 23 (13.8%) Medicare only 23 (1.1%) 23 (13.8%) Medicare Plus 323 (15.4%) 70 (10.0%) 90 (14.4%) 163 (26.9%) Private 1600 (76.3%) 616 (88.3%) 499 (79.8%) 383 (63.2%) 102 (61.1%) None 43 (2.1%) 24 (4.0%) 19 (11.4%) Clinical or Laboratory Characteristic ALT Ever measured during 2001-2010a 2173 (98.7%) 768 (99.0%) 644 (98.6%) 595 (98.2%) 166 (99.4%) Highest ever ALT in 2001–2010a Less than ULN 1103 (50.8%) 401 (52.2%) 397 (61.6%) 237 (39.8%) 68 (41.0%) >ULN to ≤2 × ULN 457 (21.0%) 171 (22.3%) 123 (19.1%) 128 (21.5%) 35 (21.1%) >2 × ULN 613 (28.2%) 196 (25.5%) 124 (19.3%) 230 (38.7%) 63 (38.0%) Most recent ALT in 2001–2010a Less than ULN 1802 (82.9%) 624 (81.3%) 572 (88.8%) 485 (81.5%) 121 (72.9%) >ULN to ≤2 × ULN 253 (11.6%) 103 (13.4%) 53 (8.2%) 68 (11.4%) 29 (17.5%) >2 × ULN 118 (5.4%) 41 (5.3%) 19 (3.0%) 42 (7.1%) 16 (9.6%) HBV RNA Ever measured during 2001-2010a 1510 (68.6%) 449 (57.9%) 464 (71.1%) 505 (83.3%) 92 (55.1%) Most recent viral load during2001–2010a,b, IU/mL Undetectable 706 (46.8%) 148 (33.0%) 224 (48.3%) 283 (56.0%) 51 (55.4%) >300 to ≤2000 (detectable) 274 (18.1%) 100 (22.3%) 101 (21.8%) 62 (12.3%) 11 (12.0%) >2000 to ≤20 000 209 (13.8%) 76 (16.9%) 66 (14.2%) 66 (13.1%) 1 (1.1%) >20 000 301 (19.9%) 125 (27.8%) 73 (15.7%) 94 (18.6%) 9 (9.8%) E-antigen Ever tested during 2001–2010a,c 1471 (66.8%) 492 (63.4%) 448 (68.6%) 422 (69.6%) 109 (65.3%) Ever e-antigen positive 431 (29.3%) 145 (29.5%) 101 (22.5%) 143 (33.9%) 42 (38.5%) Always e-antigen negative 1035 (70.4%) 345 (70.1%) 346 (77.2%) 277 (65.6%) 67 (61.5%) Most recent e-antigen positive 338 (23.0%) 118 (24.0%) 82 (18.3%) 108 (25.6%) 30 (27.5%) Most recent e-antigen negative 1128 (76.7%) 371 (75.4%) 364 (81.3%) 314 (74.4%) 79 (72.5%) Liver biopsy at least once during 2001–2010a 490 (22.3%) 151 (19.5%) 130 (19.9%) 169 (27.9%) 40 (24.0%) HIV coinfected 142 (6.4%) 54 (7.0%) 17 (2.6%) 60 (9.9%) 11 (6.6%) Ever tested for HIVa 697 (31.7%) 229 (29.5%) 221 (33.8%) 234 (38.6%) 13 (7.8%) Hospitalized Ever hospitalized during 2001–2010 835 (37.9%) 299 (38.5%) 266 (40.7%) 210 (34.7%) 60 (35.9%) Ever had liver transplant, through 2010a 46 (2.1%) 6 (0.8%) 5 (0.8%) 32 (5.3%) 3 (1.8%) Deaths, 2006–2010 Died 2006–2010 199 (9.0%) 38 (4.9%) 54 (8.3%) 83 (13.7%) 24 (14.4%) Death rate per 1000 py (95% CI) 21.6 (15.5 – 27.7) 11.2 (3.8 – 18.7) 19.9 (9.2 – 30.7) 32.6 (18.5 – 46.7) 41.5 (11.3 – 71.8) No. of deaths by birth year cohort (years of age in 2008) and death rate per 1000 py (95% CI) 1985–1990 (18–23 y) 1975–1984 (24–33 y) 3 (0.9%) Death rate 2.2 (0–7.1) 1965–1974 (34–43 y) 22 (4.4%) Death rate 10.2 (1.4–19.1) 1955–1964 (44–53 y) 44 (7.3%) Death rate 17.0 (6.7–27.3) 1945–1954 (54–63 y) 69 (15.3%) Death rate 37.1 (19.7–54.5) 1935–1944 (64–73 y) 33 (18.6%) Death rate 46.5 (15.4–77.5) ≤1934 (≥74 y) 28 (35.9%) Death rate 99.7 (33.2–166.1) Data are presented as No. (%) unless otherwise specified. Abbreviations: ALT, alanine aminotransferase; CI, confidence interval; HBV, hepatitis B virus; HIV, human immunodeficiency virus; py, person-years; ULN, upper limit of normal. a Data on these specific variables available through 2008 in Portland. b In Danville, 20 (21.7%) additional patients had a detectable viral load in units other than IU/mL. c Indeterminate e-antigen results for 5 patients not shown in table. Among the 706 (46.8%) cohort patients whose most recent quantitative HBV DNA was “undetectable” (Table 1), 409 (57.9%) had documentation of antiviral treatment. During 2001–2010, 22.3% of the HBV patients had a liver biopsy and 37.9% of cohort patients were hospitalized once or more (Table 1); on average since 2006 >9% were hospitalized each year. A number of patients (2.1% overall, range, 0.4% [Hawaii and Portland] to 5.3% [Detroit]) had undergone liver transplant for end-stage liver disease by the end of 2010 (Table 1). Data from the Kaiser sites on transplants performed at referral facilities are captured via claims data that were included in the analysis. Nine percent of these HBV cohort patients, who all had at least 1 healthcare encounter during 2006–2008, had died (any cause) by the end of 2010. Of these 199 deaths, more than half (57%) occurred among persons born between 1945 and 1964 (Table 1). ### Chronic Hepatitis C Cohort We examined the records of 1 652 055 patients aged ≥18 years in the 4 participating health systems with encounters during 2006–2008. Of note, we found that of 9086 patients with a positive HCV antibody test during 2006–2008, 3428 (37.7%) had no documented follow-up HCV RNA testing in the electronic database. A total of 9933 patients met the electronic hepatitis C cohort inclusion criteria, and after exclusion of patients for whom chronic infection was not confirmed by abstractor records review, 8810 (88.7%) remained in the cohort (Figure 2). Median observation time was 5.3 years (range, <1–17 years), with a total of 58 147 person-years of observation. Demographic and clinical features of the 8810 confirmed chronic hepatitis C cohort patients are shown in Table 2. Across all sites, almost three-quarters of the patients were born between 1945 and 1964 (Table 2). Racial and ethnic mix varied greatly by study site, ranging from 3.2% black in Hawaii to 51.6% in Detroit, and from <1% Asian/Pacific Islander in Danville to 37.2% in Hawaii. Household income was less than$30 000/year for 21.5% overall, ranging from 10.5% in Portland to 33% in Danville. Payer also varied by site; the percentage of patients using only public insurance (Medicaid or Medicare only) ranged from 2.3% in Portland to 51.0% in Danville; also, at the Danville and Detroit sites, 7.6% and 4.3% of patients respectively, were uninsured (Table 2).

Table 2.

Demographic, Clinical, and Laboratory Characteristics of Patients With Chronic Hepatitis C

Total (N = 8810) Portland, Oregon (n = 2955; 33.5%) Hawaii (n = 1040; 11.8%) Detroit, Michigan (n = 3067; 34.8%) Danville, Pennsylvania (n = 1748; 19.8%)
Demographic Characteristic
Birth year cohort (age in 2008)
1985–1990 (18–23 y) 121 (1.4%) 14 (0.5%) 17 (0.6%) 90 (5.1%)
1975–1984 (24–33 y) 407 (4.6%) 71 (2.4%) 7 (0.7%) 48 (1.6%) 281 (16.1%)
1965–1974 (34–43 y) 724 (8.2%) 264 (8.9%) 52 (5.0%) 162 (5.3%) 246 (14.1%)
1955–1964 (44–53 y) 2936 (33.3%) 1108 (37.5%) 364 (35.0%) 816 (26.6%) 648 (37.1%)
1945–1954 (54–63 y) 3704 (42.0%) 1260 (42.6%) 490 (47.1%) 1554 (50.7%) 400 (22.9%)
1935–1944 (64–73 y) 633 (7.2%) 172 (5.8%) 91 (8.8%) 322 (10.5%) 48 (2.7%)
≤1934 (≥74 y) 285 (3.2%) 66 (2.2%) 36 (3.5%) 148 (4.8%) 35 (2.0%)
Sex
Female 3554 (40.3%) 1216 (41.2%) 360 (34.6%) 1180 (38.5%) 798 (45.7%)
Male 5256 (59.7%) 1739 (58.8%) 680 (65.4%) 1887 (61.5%) 950 (54.3%)
Race/ethnicity
Race status known 7710 (87.5%) 2330 (78.8%) 784 (75.4%) 2893 (94.3%) 1703 (97.4%)
White 5361 (69.5%) 2021 (86.7%) 438 (55.9%) 1316 (45.5%) 1586 (93.1%)
Black 1751 (22.7%) 141 (6.1%) 25 (3.2%) 1493 (51.6%) 92 (5.4%)
Asian 267 (3.5%) 77 (3.3%) 122 (15.6%) 62 (2.1%) 6 (0.4%)
Pacific Islander 185 (2.4%) 14 (0.6%) 170 (21.7%) 1 (0.1%)
American Indian/Alaska Native 146 (1.9%) 77 (3.3%) 29 (3.7%) 22 (0.8%) 18 (1.1%)
Ethnicity status known 7481 (84.9%) 2022 (68.4%) 764 (73.5%) 2951 (96.2%) 1744 (99.8%)
Hispanic ethnicity 304 (4.1%) 121 (6.0%) 75 (9.8%) 51 (1.7%) 57 (3.3%)
Estimated household income (census tract geocode)
Status known 8576 (97.3%) 2940 (99.5%) 998 (96.0%) 2949 (96.2%) 1689 (96.6%)
<$15 000 198 (2.3%) 16 (0.5%) 8 (0.8%) 118 (4.0%) 56 (3.3%)$15 000–$29 000 1649 (19.2%) 292 (9.9%) 99 (9.9%) 761 (25.8%) 497 (29.4%)$30 000–$49 000 4150 (48.4%) 1575 (53.6%) 456 (45.7%) 1076 (36.5%) 1043 (61.8%)$50 000–$75 000 2064 (24.1%) 938 (31.9%) 349 (35.0%) 686 (23.3%) 91 (5.4%) >$75 000 515 (6.0%) 119 (4.0%) 86 (8.6%) 308 (10.4%) 2 (0.1%)
Insurance
Status known 8424 (95.6%) 2657 (89.9%) 952 (91.5%) 3067 (100.0%) 1748 (100.0%)
Medicaid 1021 (12.1%) 61 (2.3%) 112 (11.8%) 278 (9.1%) 570 (32.6%)
Medicare only 322 (3.8%) 322 (18.4%)
Medicare Plus 1611 (19.1%) 292 (11.0%) 152 (16.0%) 1167 (38.1%)
Private 5204 (61.8%) 2304 (86.7%) 688 (72.3%) 1489 (48.5%) 723 (41.4%)
None 266 (3.2%) 133 (4.3%) 133 (7.6%)
Laboratory or Clinical Characteristic
ALT
Ever measured during  2001–2010a 8674 (98.5%) 2924 (99.0%) 1030 (99.0%) 2997 (97.7%) 1723 (98.6%)
Highest ever ALT in 2001–2010a
Less than ULN 1787 (20.6%) 685 (23.4%) 296 (28.7%) 467 (15.6%) 339 (19.7%)
>ULN to ≤2 × ULN 2687 (31.0%) 890 (30.4%) 312 (30.3%) 980 (32.7%) 505 (29.3%)
>2 × ULN 4200 (48.4%) 1349 (46.1%) 422 (41.0%) 1550 (51.7%) 879 (51.0%)
Most recent ALT in 2001–2010a
Less than ULN 5056 (58.3%) 1622 (55.5%) 633 (61.5%) 1828 (61.0%) 973 (56.5%)
>ULN to ≤2 × ULN 2282 (26.3%) 806 (27.6%) 255 (24.8%) 773 (25.8%) 448 (26.0%)
>2 × ULN 1336 (15.4%) 496 (17.0%) 142 (13.8%) 396 (13.2%) 302 (17.5%)
HCV RNA
Ever measured during  2001–2010a 5540 (62.9%) 714 (24.2%) 898 (86.3%) 2414 (78.7%) 1514 (86.6%)
Most recent viral load during 2001–2010a, IU/mL
Undetectable 1175 (21.2%) 269 (37.7%) 179 (19.9%) 385 (15.9%) 342 (22.6%)
Detectable but ≤100 000 644 (11.6%) 70 (9.8%) 100 (11.1%) 244 (10.1%) 230 (15.2%)
>100 000 3721 (67.2%) 375 (52.5%) 619 (68.9%) 1785 (73.9%) 942 (62.2%)
Liver biopsy at least once during 2001–2010a 3380 (38.4%) 1159 (39.2%) 436 (41.9%) 1089 (35.5%) 696 (39.8%)
HIV coinfected 258 (2.9%) 69 (2.3%) 15 (1.4%) 143 (4.7%) 31 (1.8%)
Ever tested for HIVa 2436 (27.7%) 665 (22.5%) 481 (46.3%) 1245 (40.6%) 45 (2.6%)
Hospitalized
Ever hospitalized during  2001–2010 3899 (44.3%) 1281 (43.4%) 422 (40.6%) 1561 (50.9%) 635 (36.3%)
Ever had liver transplant, through 2010a 415 (4.7%) 35 (1.2%) 18 (1.7%) 319 (10.4%) 43 (2.5%)
Deaths, 2006–2010
Died 2006–2010 1229 (14.0%) 191 (6.5%) 113 (10.9%) 710 (23.1%) 215 (12.3%)
Death rate per 1000 py (95% CI) 33.0 (29.2–36.7) 14.1 (9.8–18.3) 24.9 (15.4–34.3) 57.2 (49.0–65.4) 31.9 (23.6–40.1)
No. of deaths by birth year cohort (years of age in 2008) and death rate per 1000 py (95% CI)
1985–1990 (18–23 y) 4 (3.3%)
Death rate 8.3 (0–24.5)
1975–1984 (24–33 y) 11 (2.7%)
Death rate 6.6 (0.0–14.5)
1965–1974 (34–43 y) 38 (5.2%)
Death rate 12.4 (4.3–20.4)
1955–1964 (44–53 y) 287 (9.8%)
Death rate 22.8 (17.4–28.2)
1945–1954 (54-63 y) 621 (16.8%)
Death rate 39.3 (33.1–45.6)
1935–1944 (64–73 y) 150 (23.7%)
Death rate 57.0 (39.0–75.1)
≤1934 (≥74 y) 118 (41.4%)
Death rate 110.8 (74.4–147.3)
Total (N = 8810) Portland, Oregon (n = 2955; 33.5%) Hawaii (n = 1040; 11.8%) Detroit, Michigan (n = 3067; 34.8%) Danville, Pennsylvania (n = 1748; 19.8%)
Demographic Characteristic
Birth year cohort (age in 2008)
1985–1990 (18–23 y) 121 (1.4%) 14 (0.5%) 17 (0.6%) 90 (5.1%)
1975–1984 (24–33 y) 407 (4.6%) 71 (2.4%) 7 (0.7%) 48 (1.6%) 281 (16.1%)
1965–1974 (34–43 y) 724 (8.2%) 264 (8.9%) 52 (5.0%) 162 (5.3%) 246 (14.1%)
1955–1964 (44–53 y) 2936 (33.3%) 1108 (37.5%) 364 (35.0%) 816 (26.6%) 648 (37.1%)
1945–1954 (54–63 y) 3704 (42.0%) 1260 (42.6%) 490 (47.1%) 1554 (50.7%) 400 (22.9%)
1935–1944 (64–73 y) 633 (7.2%) 172 (5.8%) 91 (8.8%) 322 (10.5%) 48 (2.7%)
≤1934 (≥74 y) 285 (3.2%) 66 (2.2%) 36 (3.5%) 148 (4.8%) 35 (2.0%)
Sex
Female 3554 (40.3%) 1216 (41.2%) 360 (34.6%) 1180 (38.5%) 798 (45.7%)
Male 5256 (59.7%) 1739 (58.8%) 680 (65.4%) 1887 (61.5%) 950 (54.3%)
Race/ethnicity
Race status known 7710 (87.5%) 2330 (78.8%) 784 (75.4%) 2893 (94.3%) 1703 (97.4%)
White 5361 (69.5%) 2021 (86.7%) 438 (55.9%) 1316 (45.5%) 1586 (93.1%)
Black 1751 (22.7%) 141 (6.1%) 25 (3.2%) 1493 (51.6%) 92 (5.4%)
Asian 267 (3.5%) 77 (3.3%) 122 (15.6%) 62 (2.1%) 6 (0.4%)
Pacific Islander 185 (2.4%) 14 (0.6%) 170 (21.7%) 1 (0.1%)
American Indian/Alaska Native 146 (1.9%) 77 (3.3%) 29 (3.7%) 22 (0.8%) 18 (1.1%)
Ethnicity status known 7481 (84.9%) 2022 (68.4%) 764 (73.5%) 2951 (96.2%) 1744 (99.8%)
Hispanic ethnicity 304 (4.1%) 121 (6.0%) 75 (9.8%) 51 (1.7%) 57 (3.3%)
Estimated household income (census tract geocode)
Status known 8576 (97.3%) 2940 (99.5%) 998 (96.0%) 2949 (96.2%) 1689 (96.6%)
<$15 000 198 (2.3%) 16 (0.5%) 8 (0.8%) 118 (4.0%) 56 (3.3%)$15 000–$29 000 1649 (19.2%) 292 (9.9%) 99 (9.9%) 761 (25.8%) 497 (29.4%)$30 000–$49 000 4150 (48.4%) 1575 (53.6%) 456 (45.7%) 1076 (36.5%) 1043 (61.8%)$50 000–$75 000 2064 (24.1%) 938 (31.9%) 349 (35.0%) 686 (23.3%) 91 (5.4%) >$75 000 515 (6.0%) 119 (4.0%) 86 (8.6%) 308 (10.4%) 2 (0.1%)
Insurance
Status known 8424 (95.6%) 2657 (89.9%) 952 (91.5%) 3067 (100.0%) 1748 (100.0%)
Medicaid 1021 (12.1%) 61 (2.3%) 112 (11.8%) 278 (9.1%) 570 (32.6%)
Medicare only 322 (3.8%) 322 (18.4%)
Medicare Plus 1611 (19.1%) 292 (11.0%) 152 (16.0%) 1167 (38.1%)
Private 5204 (61.8%) 2304 (86.7%) 688 (72.3%) 1489 (48.5%) 723 (41.4%)
None 266 (3.2%) 133 (4.3%) 133 (7.6%)
Laboratory or Clinical Characteristic
ALT
Ever measured during  2001–2010a 8674 (98.5%) 2924 (99.0%) 1030 (99.0%) 2997 (97.7%) 1723 (98.6%)
Highest ever ALT in 2001–2010a
Less than ULN 1787 (20.6%) 685 (23.4%) 296 (28.7%) 467 (15.6%) 339 (19.7%)
>ULN to ≤2 × ULN 2687 (31.0%) 890 (30.4%) 312 (30.3%) 980 (32.7%) 505 (29.3%)
>2 × ULN 4200 (48.4%) 1349 (46.1%) 422 (41.0%) 1550 (51.7%) 879 (51.0%)
Most recent ALT in 2001–2010a
Less than ULN 5056 (58.3%) 1622 (55.5%) 633 (61.5%) 1828 (61.0%) 973 (56.5%)
>ULN to ≤2 × ULN 2282 (26.3%) 806 (27.6%) 255 (24.8%) 773 (25.8%) 448 (26.0%)
>2 × ULN 1336 (15.4%) 496 (17.0%) 142 (13.8%) 396 (13.2%) 302 (17.5%)
HCV RNA
Ever measured during  2001–2010a 5540 (62.9%) 714 (24.2%) 898 (86.3%) 2414 (78.7%) 1514 (86.6%)
Most recent viral load during 2001–2010a, IU/mL
Undetectable 1175 (21.2%) 269 (37.7%) 179 (19.9%) 385 (15.9%) 342 (22.6%)
Detectable but ≤100 000 644 (11.6%) 70 (9.8%) 100 (11.1%) 244 (10.1%) 230 (15.2%)
>100 000 3721 (67.2%) 375 (52.5%) 619 (68.9%) 1785 (73.9%) 942 (62.2%)
Liver biopsy at least once during 2001–2010a 3380 (38.4%) 1159 (39.2%) 436 (41.9%) 1089 (35.5%) 696 (39.8%)
HIV coinfected 258 (2.9%) 69 (2.3%) 15 (1.4%) 143 (4.7%) 31 (1.8%)
Ever tested for HIVa 2436 (27.7%) 665 (22.5%) 481 (46.3%) 1245 (40.6%) 45 (2.6%)
Hospitalized
Ever hospitalized during  2001–2010 3899 (44.3%) 1281 (43.4%) 422 (40.6%) 1561 (50.9%) 635 (36.3%)
Ever had liver transplant, through 2010a 415 (4.7%) 35 (1.2%) 18 (1.7%) 319 (10.4%) 43 (2.5%)
Deaths, 2006–2010
Died 2006–2010 1229 (14.0%) 191 (6.5%) 113 (10.9%) 710 (23.1%) 215 (12.3%)
Death rate per 1000 py (95% CI) 33.0 (29.2–36.7) 14.1 (9.8–18.3) 24.9 (15.4–34.3) 57.2 (49.0–65.4) 31.9 (23.6–40.1)
No. of deaths by birth year cohort (years of age in 2008) and death rate per 1000 py (95% CI)
1985–1990 (18–23 y) 4 (3.3%)
Death rate 8.3 (0–24.5)
1975–1984 (24–33 y) 11 (2.7%)
Death rate 6.6 (0.0–14.5)
1965–1974 (34–43 y) 38 (5.2%)
Death rate 12.4 (4.3–20.4)
1955–1964 (44–53 y) 287 (9.8%)
Death rate 22.8 (17.4–28.2)
1945–1954 (54-63 y) 621 (16.8%)
Death rate 39.3 (33.1–45.6)
1935–1944 (64–73 y) 150 (23.7%)
Death rate 57.0 (39.0–75.1)
≤1934 (≥74 y) 118 (41.4%)
Death rate 110.8 (74.4–147.3)

Data are presented as No. (%) unless otherwise specified.

Abbreviations: ALT, alanine aminotransferase; CI, confidence interval; HCV, hepatitis C virus; HIV, human immunodeficiency virus; py, person-years; ULN, upper limit of normal.

a Data on these specific variables available through 2008 in Portland.

Among the 5540 patients (62.9% overall, range by site, 24.2%–86.6%) with quantitative HCV RNA tests during 2001–2010, recent values were undetectable for 1175 (21.2%; Table 1), of whom 937 (79.7%) patients had documentation of having received antiviral treatment. Overall in the cohort, 3211 (36.5%) had documentation of attempted antiviral treatment. During 2001–2010, 38.4% of the chronic hepatitis C patients had a liver biopsy, and 28% had ever been tested for HIV, with 2.9% testing positive. During 2001–2010, 44.3% experienced at least 1 hospitalization, and on average since 2006 >13% were hospitalized each year. Many patients (4.7%, ranging from 1.2% in Portland to 10.4% in Detroit) had undergone liver transplant for end-stage liver disease by 31 December 2010.

Fourteen percent of these HCV cohort patients, who all had at least 1 healthcare encounter during 2006–2008, had died (any cause) by the end of 2010 (Table 2). Most deaths (n = 908, 73.9%) occurred among persons in the 1945–1964 birth cohort, with an overall death rate of 33.0 per 1000 person-years (Table 2). Table 3 shows the elevated death rates per 1000 person-years in the CHeCS HCV cohort as compared with HCV antibody–negative persons in NHANES. These mortality rates were significantly elevated overall, when stratified by sex, and when stratified by age among persons aged 30–59 years.

Table 3.

All-Cause Death Rates in the CHeCS Chronic Hepatitis C Virus (HCV) Patients, 2006–2010, Compared With HCV Antibody–Negative Adults in NHANES III (1988–1994)

Deaths in CHeCSHCV Cohort, No. (%) Death Rate per 1000 pyin CHeCS Death Rate per 1000 py for HCV Antibody–Negative Adults in NHANES IIIa
All participants 1229 (100) 33.0 (29.2–36.7)c 11.1 (10.1–12.2)c
Men 836 (68.0) 37.9 (32.8–43.1)c 11.6 (10.5–12.7)c
17–29 yb 5 (0.4) 10.4 (0–28.7) 1.3 (1.5–3.4)
30–44 y 27 (2.2) 15.3 (3.7–27.0)c 2.3 (1.6–3.1)c
45–59 y 525 (42.7) 39.1 (32.4–45.8)c 11.2 (9.1–13.7)c
≥60 y 279 (22.7) 36.9 (24.9–48.9) 54.2 (49.3–59.6)
Women 393 (32.0) 25.8 (20.6–31.0)c 10.6 (9.6–11.8)c
17–29 ya 8 (0.7) 8.0 (0–8.8) 1.2 (0.8–2.0)
30–44 y 25 (2.0) 13.4 (2.7–24.0)c 1.8 (1.2–2.6)c
45–59 y 209 (17.0) 25.0 (18.1–32.0)c 8.5 (6.8–10.6)c
≥60 y 151 (12.3) 47.7 (32.7–62.7) 43.4 (39.2–47.9)
Deaths in CHeCSHCV Cohort, No. (%) Death Rate per 1000 pyin CHeCS Death Rate per 1000 py for HCV Antibody–Negative Adults in NHANES IIIa
All participants 1229 (100) 33.0 (29.2–36.7)c 11.1 (10.1–12.2)c
Men 836 (68.0) 37.9 (32.8–43.1)c 11.6 (10.5–12.7)c
17–29 yb 5 (0.4) 10.4 (0–28.7) 1.3 (1.5–3.4)
30–44 y 27 (2.2) 15.3 (3.7–27.0)c 2.3 (1.6–3.1)c
45–59 y 525 (42.7) 39.1 (32.4–45.8)c 11.2 (9.1–13.7)c
≥60 y 279 (22.7) 36.9 (24.9–48.9) 54.2 (49.3–59.6)
Women 393 (32.0) 25.8 (20.6–31.0)c 10.6 (9.6–11.8)c
17–29 ya 8 (0.7) 8.0 (0–8.8) 1.2 (0.8–2.0)
30–44 y 25 (2.0) 13.4 (2.7–24.0)c 1.8 (1.2–2.6)c
45–59 y 209 (17.0) 25.0 (18.1–32.0)c 8.5 (6.8–10.6)c
≥60 y 151 (12.3) 47.7 (32.7–62.7) 43.4 (39.2–47.9)

Abbreviations: CHeCS, Chronic Hepatitis Cohort Study; HCV, hepatitis C virus; NHANES, National Health and Nutrition Examination Survey; py, person-years.

a Among NHANES III participants 1988–1994 with mortality follow-up through 2006 [7].

b Years of age at time of death or last observation.

c Statistically significant difference (P < .05) between CHeCS and NHANES populations.

## DISCUSSION

This is the first US study to characterize a general population of >11 000 patients with chronic HBV and HCV infections and describe their substantial rates of morbidity and mortality. Rates of hospitalization were considerable; approximately 40% of both cohorts had experienced 1 or more hospitalizations during 2001–2010, with 9% of the HBV and 13% of the HCV cohorts hospitalized in an average year. Many patients (4.7% of HCV and 2.1% of HBV cohorts) had undergone liver transplant for end-stage liver disease; health systems included liver transplant centers in Detroit (since 1989) and Danville (since 2006).

The mortality rates and the relative youth of CHeCS patients who were dying were also notable. As in a recent study of 22 million death certificates from the period 1999–2007 [8], most deaths occurred among HBV- and HCV-infected persons aged 45–64 years. In particular, we found all-cause death rates among the HCV-infected CHeCS patients to be 3 times higher than those recorded among HCV-uninfected NHANES patients [7] (33.0 vs 11.1 deaths per 1000 person-years). This may partly result from the fact that the transplant centers in Detroit and Danville may augment the inclusion of patients with advanced liver disease in the CHeCS. However, the rates and percentages of deaths at the 2 nontransplant sites during the 5 years of study (11.2–19.9 deaths per 1000 person-years [4.9%–8.3%] for HBV and 14.1–24.9 deaths per 1000 person-years [6.5%–10.9%] for HCV patients) were also substantial. In summary, these high hospitalization and mortality rates, especially among those aged 30–60 years, are remarkable and worrisome.

Data from CHeCS are already yielding unique and useful information that may be used for public health action and policy development. For example, given the prevalence of infection and deaths in HCV patients in the CHeCS, our results strongly support the new policy of “birth cohort” testing of those born in 1945 through 1964 [12]. This approach is likely to be more effective than the previous risk-based testing strategy in identifying persons infected with HCV in the distant past [13].

Therapies for chronic viral hepatitis are likely to improve substantially over the coming years. Treatment results in clinical practice do not always mirror those in the clinical trial setting, particularly among minority and low-income patients with many barriers to care [10]. New patients are being added to the CHeCS dynamic cohort and records of existing patients will be updated yearly: as part of ongoing data collection, we examined the records of >1 million health system patients with encounters during 2009–2010 and identified >1200 additional chronic HBV and 3000 additional chronic HCV patients for cohort inclusion. An ongoing survey of patients in the CHeCS—of which >4500 have been completed—will further allow analyses to be adjusted for various comorbidities and conditions, such as smoking, substance use, and psychosocial measures of well-being and function. The CHeCS will address, under nonclinical trial, “real-world” conditions, issues regarding the effectiveness of evolving therapies on mortality, disease progression, adverse events, and drug resistance in a managed care population. Previously, this picture had to be estimated and pieced together from disparate and sparse data sources [11].

The CHeCS case definition algorithms applied to electronic health plan data were able to detect a large number of confirmed chronic HBV and HCV cases. While inclusion criteria based on positive nucleic acid tests (and for HBV hepatitis B surface antigen) were highly specific (>90% for HBV and >96% for HCV), use of ICD-9–based inclusion categories among patients without positive laboratory findings was of limited reliability without supplemental chart review.

CHeCS patients cannot be fully representative of chronic hepatitis B and C patients in the United States. First, these patients necessarily represent only those known to the medical care systems. As another CHeCS analysis of >1 million adult patients served by the 4 study sites has found, it appears that >21% of HBV and >43% of HCV patients in the community remain undiagnosed [9]. Institutionalized populations and the homeless are also underrepresented, although this is a limitation of almost any large study. Further, patients at 2 of the 4 participating sites are members of a health maintenance organization (Kaiser), which increases the percentage of persons with health insurance in the CHeCS as a whole.

However, these limitations should be balanced against the purposeful inclusion of Kaiser Permanente sites to make sure there was a strong representation of persons of Asian and Pacific Islander ethnicity and high numbers of HBV-infected persons. Similarly, inclusion of the sites in Detroit and central Pennsylvania assured adequate representation of Africans and African Americans and persons in important risk groups, especially injection drug users. Thus, there is good representation of minorities, the uninsured and underinsured, and those of low household income such that specific analyses of them, or analyses that adjust for their representation in the general population, can be performed.

In summary, the CHeCS is a large, multicenter study of patients with chronic hepatitis B and C that has already generated unique information about the high morbidity and mortality in this population. It is expected to yield much data-driven information about the impact of therapies, comorbidities, and conditions on the general population with HBV and HCV in the future.

## Notes

Acknowledgments. The CHeCS Investigators include the following investigators and sites: Scott D. Holmberg, Eyasu H. Teshale, Philip R. Spradling, and Anne C. Moorman, Division of Viral Hepatitis, National Centers for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia; Stuart C. Gordon, David R. Nerenz, Mei Lu, Lois Lamerato, Loralee B. Rupp, Nonna Akkerman, Nancy J. Oja-Tebbe, Chad M. Cogan, and Dana Larkin, Henry Ford Health System, Detroit, Michigan; Joseph A. Boscarino, Zahra S. Daar, Robert E. Smith, Patrick J. Curry, Brandon D. Geise, and Joe B. Leader, Geisinger Health System, Danville, Pennsylvania; Cynthia C. Nakasato, Vinutha Vijayadeva, Kelly E. Sylva, John V. Parker, and Mark M. Schmidt, Kaiser Permanente, Honolulu, Hawaii; Emily M. Henkle, Tracy L. Dodge, Erin M. Keast, and Lois Drew, Kaiser Permanente Northwest, Portland, Oregon.

Disclaimer. Granting corporations did not have access to CHeCS data and did not contribute to data analysis or writing of the manuscript.

Financial support. CHeCS was funded by the CDC Foundation, which received grants from Abbott Laboratories; Genentech, a member of the Roche Group; Janssen Pharmaceutical Companies of Johnson & Johnson; and Vertex Pharmaceuticals.

Potential conflicts of interest. S. C. G. has received grant/research support from Abbott Pharmaceuticals, Anadys Pharmaceuticals, Bristol-Myers Squibb, Conatus, Eiger Biopharmaceuticals, Exalenz BioScience, Gilead Pharmaceuticals, GlaxoSmithKline, GlobeImmune, Intercept Pharmaceuticals, Merck, Roche Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, and Zymogenetics; has served as a consultant for Achillion, Bristol-Myers Squibb, CVS Caremark, Gilead Pharmaceuticals, Merck, Salix Pharmaceuticals, Johnson & Johnson, and Vertex; has served on the data monitoring board for Tibotec; and has served as a speaker for Bayer, Gilead, Roche, Merck, and Vertex. J. A. B. has consulted for Pfizer and Janssen. All other authors report no potential conflicts.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

## References

1
Armstrong
GL
Wasley
A
Simard
EP
, et al.  .
The prevalence of hepatitis C virus infection in the United States, 1999 through 2002
Ann Intern Med
,
2006
, vol.
144
(pg.
705
-
14
)
2
Wasley
A
Kruszon-Moran
D
Kuhnert
W
, et al.  .
The prevalence of hepatitis B virus infection in the United States in the era of vaccination
J Infect Dis
,
2010
, vol.
202
(pg.
192
-
201
)
3
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, & TB Prevention
Viral hepatitis surveillance, United States
,
2009

4
Mitchell
AE
Colvin
HM
Beasley
RP
Institute of Medicine. Recommendations for the prevention and control of hepatitis B and C
Hepatol
,
2010
, vol.
52
(pg.
729
-
33
)
5
Pyenson
B
Fitch
K
Iwasaki
K
Consequences of hepatitis C virus (HCV): costs of a baby boomer epidemic of liver disease
,
2009
New York
Milliman, Inc
6
Moorman
AC
Holmberg
SD
Marlowe
SI
, et al.  .
Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV Outpatient Study (HOPS)
Ann Epidemiol
,
1999
, vol.
9
(pg.
349
-
57
)
7
El-Kamary
S
Jhaveri
R
Shardell
M
All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population
Clin Infect Dis
,
2011
, vol.
52
(pg.
150
-
7
)
8
Ly
KN
Xing
J
Klevens
M
Jiles
RB
Ward
JW
Holmberg
SD
The growing burden of mortality associated with viral hepatitis in the United States, 1999–2007
Ann Intern Med
,
2012
, vol.
156
(pg.
271
-
8
)
9
PR
Rupp
LB
Moorman
AC
, et al.  .
Predictors of testing for and infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in four United States health plans, 2006–2008
Clin Infect Dis
,
2012
, vol.
55
(pg.
1047
-
55
)
10
P
Bunim
A
Garcia
H
, et al.  .
Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients
Hepatol
,
2010
, vol.
51
(pg.
1137
-
43
)
11
Cohen
C
Holmberg
SD
McMahon
BJ
, et al.  .
Is chronic hepatitis B being undertreated in the United States?
J Viral Hepatitis
,
2011
, vol.
18
(pg.
377
-
83
)
12
Centers for Disease Control and Prevention
Recommendations for the identification and initial care of chronic hepatitis C virus infection among persons born during 1945–1965
MMWR
,
2012
61 No
pg.
RR-4

In press, planned publication date 17 August 2012
13
Rein
DB
Smith
BD
Wittenborn
JS
, et al.  .
The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings
Ann Intern Med
,
2012
, vol.
156
(pg.
263
-
70
)

## Author notes

a
The CHeCS investigators are listed in the Acknowledgments.