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Hepatitis C Infection Screening and Management in Opioid Use Epidemics in the United States

      Acute Hepatitis C and Heroin Use Epidemics in the United States

      Acute hepatitis C infection is on the rise in the United States, with a more than twofold increase in incidence rate from 2003 to 2016 overall and a threefold increase among young adults
      • Zibell JE
      • Asher AK
      • Patel RC
      • et al.
      Increase in acute hepatitis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      (Figure). In 2016, a total of 2967 cases were reported from 42 states, and the Centers for Disease Control and Prevention estimates the actual case number to be 41,200.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      This national increase in acute hepatitis C infection has mirrored reports of escalating injection drug use.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      Heroin injection is known to be a major route of hepatitis C transmission, and young adults are increasingly shifting from other opiates to heroin due to its lower price and easier accessibility as prescription opioids become more difficult to acquire amid concern for an epidemic of opiate addiction.

      Volkow N. Prescription opioid and heroin abuse: Testimony to Congress, April 29, 2014. National Institute on Drug Abuse. Available at: https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2018/prescription-opioid-heroin-abuse. Accessed April 18, 2018.

      • Chai G
      • Xu J
      • Osterhout J
      • et al.
      New opioid analgesic approvals and outpatient utilization of opioid analgesics in the United States, 1997 through 2015.
      The cumulative incidence rate of hepatitis C virus was reported to be 28% at 1 year of drug injection.
      • Hagan H
      • Pouget ER
      • Des Jarlais DC
      • Lelutiu-Weinberger C
      Meta-regression of hepatitis C virus infection in relation to time since onset of illicit drug injection: The influence of time and place.
      In 2016, nearly 1 million Americans reported using heroin.
      • DeShazo R
      • Johnson M
      • Eriator I
      • Rodenmeyer K
      Backstories on the U.S. opioid epidemic: Good intentions gone bad, an industry gone rogue and watch dogs gone to sleep.
      Groups at high risk for hepatitis C infection include young adults, males, and whites, the same groups at risk for heroin use.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      Although decreases in prescription opioids correspond to national, state, and local initiatives that target opioid prescribing, public health stakeholders are alarmed at rising trends in heroin-associated hospital and emergency department utilizations.
      Substance Abuse and Mental Health Services Administration
      Key Substance Use and Mental Health Indicators in the United States: Results from the 2016 National Survey on Drug Use and Health.
      • Tedesco D
      • Asch SM
      • Curtin C
      • et al.
      Opioid abuse and poisoning: Trends in inpatient and emergency department discharges.
      Nationally representative face-to-face interviews provide further evidence for increasing use of heroin, with greater increases among white individuals.
      • Martins SS
      • Sarvet A
      • Santella-Tenorio J
      • Saha T
      • Grant BF
      • Hasin DS
      Changes in US lifetime heroin use and heroin use disorder prevalence from the 2001-2002 to 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions.
      Fig 1
      FigureTime trends of acute hepatitis C incidence by age groups: 2003-2016.

      Unequal Access to Cost-Effective Direct-Acting Antiviral Therapy in the United States

      Direct-acting antiviral (DAA) therapy to eradicate hepatitis C virus is highly cost-effective, with an excellent tolerability profile.
      • Chhatwal J
      • He T
      • Hur C
      • Lopez-Olivo MA
      Direct-acting antiviral agents for patients with hepatitis C virus genotype 1 infection are cost-saving.
      Even so, considerable heterogeneity remains across state Medicaid programs in the criteria for approving DAA therapy.
      • Ooka K
      • Connolly JJ
      • Lim JK
      Medicaid reimbursement for oral direct antiviral agents for the treatment of chronic hepatitis C.
      DAA therapy is accessible mainly through state Medicaid programs among low-income and nonelderly populations that are at high risk for injection drug use and acute hepatitis C.
      • Ooka K
      • Connolly JJ
      • Lim JK
      Medicaid reimbursement for oral direct antiviral agents for the treatment of chronic hepatitis C.
      There are remarkable, unmet needs for DAA therapy among prison inmates with hepatitis C; less than 1% of state inmates are reported to receive DAA therapy, even though the prevalence of hepatitis C is estimated to be more than 10 times greater in inmates than in noninstitutionalized US populations.
      • He T
      • Li K
      • Roberts MS
      • et al.
      Prevention of hepatitis C by screening and treatment in U.S. prisons.
      • Beckman AL
      • Billinski A
      • Boyko R
      • et al.
      New hepatitis C drugs are very costly and unavailable to many state prisoners.
      Because many inmates will eventually return to public life, coordinated strategies for affordable and accessible DAA therapy are needed in this high-risk population.

      Hepatitis C Screening Strategies in the United States

      The current hepatitis C screening strategy is a 1-time testing of the baby boomer cohort born between 1945 and 1965, as recommended by the US Centers for Disease Control and Prevention in 2012 and endorsed by the US Preventative Services Task Force in 2013.

      United States Preventive Services Task Force (USPSTF). Final recommendation statement: Hepatitis C: Screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening. Accessed April 17, 2018.

      • Koretz RL
      • Lin KW
      • Ioannidis JP
      • Lenzer J
      Is widespread screening for hepatitis C justified?.
      • Chou R
      • Cottrell EB
      • Wasson N
      • Rahman B
      • Guise JM
      Screening for hepatitis C virus infection in adults: a systematic review for the U.S. Preventive Services Task Force.
      As seen in the Figure, part of the increase in acute hepatitis infection rate is attributable to the newly expanded screening guidelines. However, increases in the 0-29–year age group are not explained by that window.
      A recent comparative effectiveness analysis suggests that screening the entire US population would be more cost-effective than the current birth cohort strategy, given the high risk of injection drug users.
      • Younossi Z
      • Blissett D
      • Blissett R
      • et al.
      In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered.
      However, this analysis has limitations and does not reflect secular opioid epidemic trends.
      • Younossi Z
      • Blissett D
      • Blissett R
      • et al.
      In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered.

      Substance Use Disorder and Hepatitis C Treatment Under Health Care Reform

      Historically, substance use disorder treatment services have been constrained by the application of higher copayments, limitation of annual visits, and placement of medications into higher tiers.
      • Barry CL
      • Huskamp HA
      • Goldman HH
      A political history of federal mental health and addiction insurance parity.
      The Affordable Care Act (ACA) drastically changed the landscape by providing greater access to substance use disorder treatment through a major expansion of coverage, enhancement of parity protection to major health plans, and integration with comorbidities such as hepatitis C, human immune deficiency infection, and mental health.
      • Abraham AJ
      • Andrews CM
      • Grogan CM
      • et al.
      The Affordable Care Act transformation of substance use disorder treatment.
      An estimated 1.6 million Americans with substance use disorders have gained insurance coverage in Medicaid expansion states.

      Henry J. Kaiser Family Foundation. Current status of state Medicaid expansion decisions. Available at: https://www.kff.org/health-reform/slide/current-status-of-the-medicaid-expansion-decision/. Accessed April 18, 2018.

      The ACA also grants parental insurance coverage to adult children up to the age of 26 years, a population with higher rates of opioid use disorder, and bans insurers from refusing service to individuals with pre-existing opioid use disorders.
      • Abraham AJ
      • Andrews CM
      • Grogan CM
      • et al.
      The Affordable Care Act transformation of substance use disorder treatment.
      As of June 2018, 33 states and Washington, DC, had adopted Medicaid expansion and state insurance exchange programs, the primary means by which the ACA extends insurance coverage.
      • Abraham AJ
      • Andrews CM
      • Grogan CM
      • et al.
      The Affordable Care Act transformation of substance use disorder treatment.

      Henry J. Kaiser Family Foundation. Current status of state Medicaid expansion decisions. Available at: https://www.kff.org/health-reform/slide/current-status-of-the-medicaid-expansion-decision/. Accessed April 18, 2018.

      However, considerable gaps remain in health care access among many substance use disorder patients based on the decision of some states to forgo Medicaid expansion. Uncertainty remains about the current administration's actions on substance use disorders and DAA therapy coverage. The major challenge facing the American Health Care Act (H.R. 1628, 2017) is the loss of insurance coverage for an estimated more than 20 million adults in the United States.

      Congressional Budget Office. How CBO Produces Fair-Value Estimates of the Cost of Federal Credit Programs: A Primer. American Health Care Act of 2017. Available at: https://www.cbo.gov/system/files/115th-congress-2017-2018/costetimate/hr1628aspassed.pdf. Accessed February 24, 2018.

      Uninsured substance use disorder patients, with or without hepatitis C, are expected to be more vulnerable to worsened health outcomes than those with Medicaid benefits through the ACA.

      Marijuana Legalization Laws and the Opioid Epidemic

      As more states expand access to legal marijuana, further investigation is warranted of time trends and dynamics between marijuana legalization and nonprescribed opioid use, including the criminal use of opioids among high-risk populations of heroin users and those with acute hepatitis. Although medical marijuana laws are associated with a reduction in overdose deaths from opioid pain relievers,
      • Shi Y
      Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever.
      the effect of marijuana legalization on both prescribed and illicit opioid use needs further attention. Medical marijuana laws appear to have advanced an unhealthy social contagion of substance use in general, contributing to a collective trend toward the passage of recreational marijuana legalization laws, according to the 3 nationally representing US adult surveys.
      • Hasin DS
      • Sarvet AL
      • Cerda M
      • et al.
      US adults illicit cannabis use, cannabis use disorder, and medical marijuana laws 1991–1992 to 2012–2013.
      Marijuana may play the role of “gateway” or “stepping stone” drug to hard drugs such as heroin among high-risk injection drug users, due to familiarity and receptiveness of substance use.
      • Hall W
      • Lynskey M
      Why it is probably too soon to assess the public health effects of legalisation of recereational cannabis use in the USA.
      The national growth of hepatitis C infections could be the by-product of increases in injection drug use in conjunction with socially acceptable substance use stemming from marijuana legalization.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      Further research analyzing state-level data and comparing heroin, hepatitis C, and marijuana-associated hospitalization or emergency department visits and drug-related crime incidents between states with and without legal marijuana access should be considered.

      “Call to Action” for the Revision of Hepatitis C Screening Recommendations

      A “call to action” is urgently warranted for physicians and public health stakeholders to revise the Centers for Disease Control and Prevention and the US Preventative Services Task Force recommendations

      United States Preventive Services Task Force (USPSTF). Final recommendation statement: Hepatitis C: Screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening. Accessed April 17, 2018.

      of hepatitis C screening from the current baby boomer cohort born between 1945 and 1965 to screening of all US adults. More affordable ways must be identified to expand screening and access to health care for those at high risk of injection drug use and hepatitis C, particularly among young adults, males, and whites.

      Centers for Disease Control and Prevention. Surveillance for vital hepatitis–United States, 2016. Available at: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm. Accessed April 17, 2018.

      Further studies should examine the comparative effectiveness of patient-centered care and health care delivery models to facilitate revisions of the current hepatitis C screening recommendations.

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