Estimating High-Priority Patients in the US With Chronic HCV
Estimating High-Priority Patients in the US With Chronic HCV
Of an estimated 2.7 million people (95% CI = 2.2, 3.2) infected with chronic HCV in the United States, most (79%) were aged between 40 and 59 years at the time of the NHANES survey. A majority of HCV-infected people were male (64%) and non-Hispanic White (61%). On the basis of FIB-4 scores among HCV-infected NHANES participants, we estimated that 351 000 people (95% CI = 216 000, 540 000), or 13% (95% CI = 8%, 20%), had an FIB-4 score of 3.25 or higher, predictive of advanced fibrosis (METAVIR F3 or higher). Using the more inclusive threshold of 2.5 (instead of 3.25), we estimated that the number of people with advanced fibrosis of METAVIR F3 or higher was 513 000 (95% CI = 378 000, 675 000), or 19% (95% CI = 14%, 25%; Table 1). After adding 18 900 people (95% CI = 5400, 54 000) who had an FIB-4 score of less than 2.5 but who might qualify because of a urinary test indicating proteinuria (Appendix A), the national estimate for people meeting the highest criteria for treatment was 532 000 (95% CI = 392 000, 702 000; Table 1).
After excluding those meeting the highest criteria for treatment, we estimated that 405 000 people (95% CI = 297 000, 567 000) had an FIB-4 score of 1.6 or more (but < 2.5), predictive of METAVIR F2 (Table 1). After adding in people with comorbid conditions such as HIV coinfection (Appendix A), the national estimate for people meeting the high-priority criteria for treatment was 513 000 (95% CI = 386 000, 699 000). In total, we estimated that about 1.0 million people (532 000 + 513 000; 95% CI = 875 000, 1 245 000) met highest or high-priority criteria in the United States; the majority (81%; 95% CI = 73%, 87%) of these people were born between 1945 and 1965.
If one assumes that 50% of the 2.7 million HCV-infected people have been tested and confirmed positive—that is, known to be HCV infected—then 1.35 million people are living with a diagnosed chronic HCV infection. We estimated the distribution of fibrotic stage and comorbid conditions among people whose HCV infection had been diagnosed from CHeCS data. From among the 14 708 CHeCS patients with confirmed HCV infection, we excluded 3922 who had died, achieved sustained virologic response, or received a liver transplant while under observation. Of the remaining 10 786 patients, we excluded 6% because they had no biopsy and no laboratory tests for FIB-4 calculation, which suggested that they had received little workup or had been lost to follow-up. Of the remaining 94%, 22% had at least 1 liver biopsy in 2004 or later, and 72% had at least 1 FIB-4 measurement without biopsy. When we applied these percentages to the national estimate of HCV-infected people, the result was 297 000 people (22% of 1.35 million) with at least 1 liver biopsy and 972 000 people (72% of 1.35 million) with at least 1 FIB-4 measurement without biopsy (Figure 1).
(Enlarge Image)
Figure 1.
Cascade diagram of the estimated number of people infected with HCV in the United States according to diagnosis status and hierarchy of care: 2003–2010 National Health and Nutrition Examination Survey; Chronic Hepatitis Cohort Study, January 1, 2006–December 31, 2012.
Note. AASLD/IDSA = American Association for the Study of Liver Diseases–Infectious Diseases Society of America; ALT = alanine aminotransferase; AST = aspartate aminotransferase. FIB-4 score = [age × AST (IU/L)]/[platelet (10/L) × ALT ½ (IU/L)]. FIB-4 score is calculated from routine liver function tests (ALT and AST) and platelet count test; the number of patients for whom an FIB-4 score was ordered for the purpose of treating HCV infection is unknown. An FIB-4 score ≥ 2.5 is predictive of advanced fibrosis (METAVIR F3 or higher), and an FIB-4 score ≥ 1.6 but < 2.5 is predictive of advanced fibrosis (METAVIR F2). American Association for the Study of Liver Diseases–Infectious Diseases Society of America highest or high-priority treatment criteria are based on When and in Whom to Initiate HCV Therapy. Chronic conditions are coinfections or comorbidities including HIV, hepatitis B virus, diabetes, and coexistent liver condition (e.g., nonalcoholic steatohepatitis) in HCV-diagnosed patients only (see Appendix A, available as a supplement to the online version of this article at http://www.ajph.org).
See Denniston et al.
See Spradling et al. and Denniston et al.
See Holmberg et al.
Demographic characteristics of CHeCS patients mirrored those among HCV-infected participants in NHANES. The mean age at the end of 2012 for CHeCS patients was 54.4 years, 58% were male, and 62% were non-Hispanic White. However, CHeCS patients were more likely to have advanced liver disease than HCV-infected NHANES participants. After matching by birth year, the percentages of people with an FIB-4 score of 3.25 or higher were 20% among CHeCS patients and 7% higher than the 13% estimated among HCV-infected NHANES participants.
We based stage of liver disease among CHeCS patients (whose HCV infection had been diagnosed) on biopsy results when available (as early as 2004) and on FIB-4 scores when biopsy results were not available. From the results of the most recent biopsies, we estimated that 27% of CHeCS patients were at METAVIR F3 or F4. When we supplemented the most recent biopsy results with the most recent measurement of FIB-4 score, using 2.5 or higher as the threshold, we estimated that 33% of CHeCS patients were at METAVIR F3 or F4. Applying this value to the national estimate of HCV patients (Figure 1) results in an estimated 419 000 people nationwide (33% of 1.27 million) meeting the high-priority criteria for treatment. Among CHeCS patients, 3% were identified as having a fibrosis level less than METAVIR F3 but as perhaps qualifying as highest priority because of evidence of kidney disease (Appendix A). The total estimated number of people categorized as meeting the criteria for highest treatment priority was 457 000 nationwide (36%; Figure 1).
Among the remaining CHeCS patients who did not meet the highest priority treatment criteria but who might potentially have met the high-priority treatment criteria, 28% had evidence of moderate fibrosis (METAVIR F2 by biopsy or FIB-4 ≥ 1.6 and < 2.5) or had a qualifying coinfection or comorbidity, corresponding to 356 000 (28% of 1.27 million) people nationwide. In total, the national estimate of people meeting highest or high-priority criteria was 813 000, or about 64% of those living with a diagnosed chronic HCV infection (Figure 1).
Results
Of an estimated 2.7 million people (95% CI = 2.2, 3.2) infected with chronic HCV in the United States, most (79%) were aged between 40 and 59 years at the time of the NHANES survey. A majority of HCV-infected people were male (64%) and non-Hispanic White (61%). On the basis of FIB-4 scores among HCV-infected NHANES participants, we estimated that 351 000 people (95% CI = 216 000, 540 000), or 13% (95% CI = 8%, 20%), had an FIB-4 score of 3.25 or higher, predictive of advanced fibrosis (METAVIR F3 or higher). Using the more inclusive threshold of 2.5 (instead of 3.25), we estimated that the number of people with advanced fibrosis of METAVIR F3 or higher was 513 000 (95% CI = 378 000, 675 000), or 19% (95% CI = 14%, 25%; Table 1). After adding 18 900 people (95% CI = 5400, 54 000) who had an FIB-4 score of less than 2.5 but who might qualify because of a urinary test indicating proteinuria (Appendix A), the national estimate for people meeting the highest criteria for treatment was 532 000 (95% CI = 392 000, 702 000; Table 1).
After excluding those meeting the highest criteria for treatment, we estimated that 405 000 people (95% CI = 297 000, 567 000) had an FIB-4 score of 1.6 or more (but < 2.5), predictive of METAVIR F2 (Table 1). After adding in people with comorbid conditions such as HIV coinfection (Appendix A), the national estimate for people meeting the high-priority criteria for treatment was 513 000 (95% CI = 386 000, 699 000). In total, we estimated that about 1.0 million people (532 000 + 513 000; 95% CI = 875 000, 1 245 000) met highest or high-priority criteria in the United States; the majority (81%; 95% CI = 73%, 87%) of these people were born between 1945 and 1965.
If one assumes that 50% of the 2.7 million HCV-infected people have been tested and confirmed positive—that is, known to be HCV infected—then 1.35 million people are living with a diagnosed chronic HCV infection. We estimated the distribution of fibrotic stage and comorbid conditions among people whose HCV infection had been diagnosed from CHeCS data. From among the 14 708 CHeCS patients with confirmed HCV infection, we excluded 3922 who had died, achieved sustained virologic response, or received a liver transplant while under observation. Of the remaining 10 786 patients, we excluded 6% because they had no biopsy and no laboratory tests for FIB-4 calculation, which suggested that they had received little workup or had been lost to follow-up. Of the remaining 94%, 22% had at least 1 liver biopsy in 2004 or later, and 72% had at least 1 FIB-4 measurement without biopsy. When we applied these percentages to the national estimate of HCV-infected people, the result was 297 000 people (22% of 1.35 million) with at least 1 liver biopsy and 972 000 people (72% of 1.35 million) with at least 1 FIB-4 measurement without biopsy (Figure 1).
(Enlarge Image)
Figure 1.
Cascade diagram of the estimated number of people infected with HCV in the United States according to diagnosis status and hierarchy of care: 2003–2010 National Health and Nutrition Examination Survey; Chronic Hepatitis Cohort Study, January 1, 2006–December 31, 2012.
Note. AASLD/IDSA = American Association for the Study of Liver Diseases–Infectious Diseases Society of America; ALT = alanine aminotransferase; AST = aspartate aminotransferase. FIB-4 score = [age × AST (IU/L)]/[platelet (10/L) × ALT ½ (IU/L)]. FIB-4 score is calculated from routine liver function tests (ALT and AST) and platelet count test; the number of patients for whom an FIB-4 score was ordered for the purpose of treating HCV infection is unknown. An FIB-4 score ≥ 2.5 is predictive of advanced fibrosis (METAVIR F3 or higher), and an FIB-4 score ≥ 1.6 but < 2.5 is predictive of advanced fibrosis (METAVIR F2). American Association for the Study of Liver Diseases–Infectious Diseases Society of America highest or high-priority treatment criteria are based on When and in Whom to Initiate HCV Therapy. Chronic conditions are coinfections or comorbidities including HIV, hepatitis B virus, diabetes, and coexistent liver condition (e.g., nonalcoholic steatohepatitis) in HCV-diagnosed patients only (see Appendix A, available as a supplement to the online version of this article at http://www.ajph.org).
See Denniston et al.
See Spradling et al. and Denniston et al.
See Holmberg et al.
Demographic characteristics of CHeCS patients mirrored those among HCV-infected participants in NHANES. The mean age at the end of 2012 for CHeCS patients was 54.4 years, 58% were male, and 62% were non-Hispanic White. However, CHeCS patients were more likely to have advanced liver disease than HCV-infected NHANES participants. After matching by birth year, the percentages of people with an FIB-4 score of 3.25 or higher were 20% among CHeCS patients and 7% higher than the 13% estimated among HCV-infected NHANES participants.
We based stage of liver disease among CHeCS patients (whose HCV infection had been diagnosed) on biopsy results when available (as early as 2004) and on FIB-4 scores when biopsy results were not available. From the results of the most recent biopsies, we estimated that 27% of CHeCS patients were at METAVIR F3 or F4. When we supplemented the most recent biopsy results with the most recent measurement of FIB-4 score, using 2.5 or higher as the threshold, we estimated that 33% of CHeCS patients were at METAVIR F3 or F4. Applying this value to the national estimate of HCV patients (Figure 1) results in an estimated 419 000 people nationwide (33% of 1.27 million) meeting the high-priority criteria for treatment. Among CHeCS patients, 3% were identified as having a fibrosis level less than METAVIR F3 but as perhaps qualifying as highest priority because of evidence of kidney disease (Appendix A). The total estimated number of people categorized as meeting the criteria for highest treatment priority was 457 000 nationwide (36%; Figure 1).
Among the remaining CHeCS patients who did not meet the highest priority treatment criteria but who might potentially have met the high-priority treatment criteria, 28% had evidence of moderate fibrosis (METAVIR F2 by biopsy or FIB-4 ≥ 1.6 and < 2.5) or had a qualifying coinfection or comorbidity, corresponding to 356 000 (28% of 1.27 million) people nationwide. In total, the national estimate of people meeting highest or high-priority criteria was 813 000, or about 64% of those living with a diagnosed chronic HCV infection (Figure 1).
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