Estimating High-Priority Patients in the US With Chronic HCV
Estimating High-Priority Patients in the US With Chronic HCV
We estimate that about 1 million noninstitutionalized people with HCV infection in the United States met the highest or high-priority criteria for treatment. Of these, we estimate that 813 000 people had been diagnosed and were in care. By estimating the number of HCV-infected people who have been diagnosed and met treatment criteria, we hope to inform planning and other efforts to address barriers to HCV treatment, including enhanced clinical capacity and budgetary projections.
Our results may constitute overestimates of the highest or high-priority treatment populations who will be treated in the short term because the staging of liver disease in this analysis was mostly based on FIB-4 score, and only a relatively few patients (22% of CHeCS patients) had been biopsied. The laboratory tests that allowed us to obtain an FIB-4 score were not necessarily ordered to assess a patient's need for treatment. Therefore, the number of patients for whom the tests were ordered for the purpose of treating HCV infection is presumably low. Thus, these estimates likely represent the maximum number of people currently in care who should get immediate therapy because clinicians may not be aware that their patients are at a stage of liver disease that qualifies them for prioritization. Even for those known to have a more advanced stage of liver disease, life-limiting conditions, deaths, and patient or physician choice may limit the number of those patients receiving new antiviral therapies.
Chronic HCV infection is not widely acknowledged as an urgent public health issue despite increasing health system burden and mortality. In the United States, decedents with HCV infection listed among the causes of death on their death certificates were more than 20 years younger than decedents without HCV infection. Thus, the need to treat those at most risk of immediate mortality and morbidity is urgent.
The findings of this study are subject to several limitations. Our estimates are limited to the civilian noninstitutionalized population. The NHANES does not include homeless individuals, active military members, or people residing outside of households, such as in nursing homes or in prisons. The use of data from NHANES 2003 to 2010 may have resulted in a slight underestimation of the number of patients with advanced fibrosis due to disease progression in more recent years. Also, the number of people qualifying for treatment was mostly based on FIB-4 values. The purpose of using the FIB-4 score in this analysis was to estimate how many patients qualified as highest or high priority for treatment at the national level, and we chose the FIB-4 score thresholds of 2.5 and 1.6 on the basis of the upper limits of mean FIB-4 scores to balance the chances of underestimation and overestimation. These thresholds may be different from the cutoffs that maximize sensitivity and specificity at the patient level and have not been evaluated for their positive predictive value and negative predictive value at the individual level. Incidentally, in a recent analysis, FIB-4 scores of 2.5 or more were associated with increased incidence of hepatocellular carcinoma, which is among the most severe complications of chronic, untreated HCV infection. Despite the fact that CHeCS cohort is large and geographically and clinically diverse, the CHeCS patients' distribution by fibrosis stage may not be generalizable to all people who have been diagnosed with chronic HCV infection. Finally, we did not include some comorbid conditions, such as debilitating fatigue, because of the absence of data (Appendix A). However, generally speaking, the prevalence of comorbid conditions in people with mild liver disease (< METAVIR F2) is expected to be low.
Potential demand for HCV treatment may require rapid and substantial increases in clinical capacity. However, although widespread initiation of HCV therapies may be associated with substantial and perhaps prohibitive costs, estimating the number of people actually ready for therapy—as we have done—may provide useful information as to the affordability of particular treatment policies and priorities. Increasing morbidity and mortality rates and the associated health system costs and burdens that result from chronic HCV infection can potentially be reduced if barriers to uptake of therapy for HCV infection are addressed.
Discussion
We estimate that about 1 million noninstitutionalized people with HCV infection in the United States met the highest or high-priority criteria for treatment. Of these, we estimate that 813 000 people had been diagnosed and were in care. By estimating the number of HCV-infected people who have been diagnosed and met treatment criteria, we hope to inform planning and other efforts to address barriers to HCV treatment, including enhanced clinical capacity and budgetary projections.
Our results may constitute overestimates of the highest or high-priority treatment populations who will be treated in the short term because the staging of liver disease in this analysis was mostly based on FIB-4 score, and only a relatively few patients (22% of CHeCS patients) had been biopsied. The laboratory tests that allowed us to obtain an FIB-4 score were not necessarily ordered to assess a patient's need for treatment. Therefore, the number of patients for whom the tests were ordered for the purpose of treating HCV infection is presumably low. Thus, these estimates likely represent the maximum number of people currently in care who should get immediate therapy because clinicians may not be aware that their patients are at a stage of liver disease that qualifies them for prioritization. Even for those known to have a more advanced stage of liver disease, life-limiting conditions, deaths, and patient or physician choice may limit the number of those patients receiving new antiviral therapies.
Chronic HCV infection is not widely acknowledged as an urgent public health issue despite increasing health system burden and mortality. In the United States, decedents with HCV infection listed among the causes of death on their death certificates were more than 20 years younger than decedents without HCV infection. Thus, the need to treat those at most risk of immediate mortality and morbidity is urgent.
The findings of this study are subject to several limitations. Our estimates are limited to the civilian noninstitutionalized population. The NHANES does not include homeless individuals, active military members, or people residing outside of households, such as in nursing homes or in prisons. The use of data from NHANES 2003 to 2010 may have resulted in a slight underestimation of the number of patients with advanced fibrosis due to disease progression in more recent years. Also, the number of people qualifying for treatment was mostly based on FIB-4 values. The purpose of using the FIB-4 score in this analysis was to estimate how many patients qualified as highest or high priority for treatment at the national level, and we chose the FIB-4 score thresholds of 2.5 and 1.6 on the basis of the upper limits of mean FIB-4 scores to balance the chances of underestimation and overestimation. These thresholds may be different from the cutoffs that maximize sensitivity and specificity at the patient level and have not been evaluated for their positive predictive value and negative predictive value at the individual level. Incidentally, in a recent analysis, FIB-4 scores of 2.5 or more were associated with increased incidence of hepatocellular carcinoma, which is among the most severe complications of chronic, untreated HCV infection. Despite the fact that CHeCS cohort is large and geographically and clinically diverse, the CHeCS patients' distribution by fibrosis stage may not be generalizable to all people who have been diagnosed with chronic HCV infection. Finally, we did not include some comorbid conditions, such as debilitating fatigue, because of the absence of data (Appendix A). However, generally speaking, the prevalence of comorbid conditions in people with mild liver disease (< METAVIR F2) is expected to be low.
Potential demand for HCV treatment may require rapid and substantial increases in clinical capacity. However, although widespread initiation of HCV therapies may be associated with substantial and perhaps prohibitive costs, estimating the number of people actually ready for therapy—as we have done—may provide useful information as to the affordability of particular treatment policies and priorities. Increasing morbidity and mortality rates and the associated health system costs and burdens that result from chronic HCV infection can potentially be reduced if barriers to uptake of therapy for HCV infection are addressed.
