Screening for HCV Infection

Hepatitis C Virus Infection Guideline Committee, updated August 2018

More than 50% of people with chronic hepatitis C virus (HCV) infection may not be aware of their infection. Because approximately 75% of cases are among persons born between 1945 and 1965 [Denniston et al. 2012; Armstrong et al. 2006; CDC 2013], age-cohort screening of asymptomatic adults with no recognized risk factors is thought to increase identification and treatment for these patients. In addition to required HCV screening in the specific birth cohort, healthcare providers should screen patients with other risk factors for HCV infection (see the Risk-Based Screening section of this guideline).

In May 2018, the AASLD/IDSA updated its HCV Guidance to include a recommendation supporting universal screening for HCV in pregnant women. The HCV Committee of the NYSDOH AI Clinical Guidelines Program agrees with this recommendation.

As part of HCV screening and diagnosis, a series of serologic and virologic tests are used, including laboratory-based antibody tests, point-of-care rapid HCV antibody tests for initial screening, and laboratory-based HCV RNA tests for HCV diagnosis.

KEY POINT: REPORTING
  • New York State (NYS) Public Health law mandates that clinicians report all suspected or confirmed cases of HCV infection, specifying acute or chronic, to the local health department of the area where the patient resides.
References

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;144(10):705-14. [PMID: 16702586]

Centers for Disease Control and Prevention (CDC). Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep 2013;62(18):362-5. [PMID: 23657112]

Denniston MM, Klevens RM, McQuillan GM, et al. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008. Hepatology 2012;55(6):1652-61. [PMID: 22213025]

Cohort-Based

Hepatitis C Virus Infection Guideline Committee, updated August 2018

NEW YORK STATE REQUIREMENT
Cohort-Based Screening
  • REQUIREMENT: New York State (NYS) Public Health Law mandates that primary care clinicians offer hepatitis C virus (HCV) screening to individuals born from 1945 to 1965 in a culturally and linguistically appropriate manner.

In NYS, physicians, physician assistants, and nurse practitioners delivering primary care must provide HCV screening, regardless of setting and without regard to certification. Care providers working in hospitals (inpatient units and outpatient clinics) and other healthcare settings where primary care services are being delivered are also required to offer HCV screening. Emergency departments are not required by law to offer HCV screening, but in NYS, they are encouraged to do so.

If the initial screening is reactive, clinicians must offer follow-up healthcare, including HCV diagnostic testing, or refer the patient to a liver disease specialist. By requiring HCV antibody screening for this age cohort in traditional medical settings and supporting screening efforts in community-based locations, NYS is actively seeking to identify people with chronic HCV infection and link them to treatment before irreversible liver damage occurs.

In response to the law, hospitals, clinics, health centers, and other primary care medical facilities have established HCV screening programs. During the first year of implementing the law, there was a 51% increase in specimens submitted for HCV testing. Testing rates among active Medicaid clients increased 52%. Among persons with newly diagnosed HCV infection, linkage to care increased approximately 40% in NYS (excluding New York City) and 11% in New York City [Flanigan et al. 2017].

However, people with HCV infection may face significant barriers to accessing care in clinical settings, including lack of health insurance, physical disability, ongoing substance use, mental health disorders, and housing instability. Locating HCV screening sites in a variety of community-based organizations, such as syringe exchange programs, sexually transmitted disease (STI) clinics, and local health departments, is integral to the effort to provide HCV screening, treatment, and education in diverse settings.

Birth cohort screening is particularly important because patients may not be aware of or remember exposures or may not disclose prior behavioral risks for HCV infection (see the Risk-Based Screening section of this guideline). Patient education is needed to ensure that patients know about risk factors for transmitting or acquiring HCV infection. While birth cohort screening is important, screening for HCV beyond the required birth cohort is needed in areas where HCV prevalence is high.

KEY POINTS
  • Cohort and risk-based screening are both crucial to identifying adults with HCV infection.
  • In geographical areas with high HCV prevalence, screening should be performed in all people who may have been exposed to HCV through any means of transmission.
  • In addition to screening all individuals born from 1945 to 1965, the HCV AI Guidelines Committee agrees with the AASLD/IDSA recommendation to screen all pregnant individuals for HCV. 
Reference

Flanigan CA, Leung SJ, Rowe KA, et al. Evaluation of the Impact of Mandating Health Care Providers to Offer Hepatitis C Virus Screening to All Persons Born During 1945-1965 – New York, 2014. MMWR Morb Mortal Wkly Rep 2017;66(38):1023-26. [PMID: 28957037]

Risk-Based

Hepatitis C Virus Infection Guideline Committee, December 2017

RECOMMENDATIONS
Risk-Based Screening
  • Clinicians should perform hepatitis C virus (HCV) screening at least once for patients of any age who are not known to have HCV infection and currently have, or have a history that includes, any of the following risk factors:
  • Clinicians should offer HCV screening at least annually to individuals who are not known to have HCV infection and:
    • Use injection drugs (A2)
    • Use intranasal drugs (A2)
    • Receive current long-term hemodialysis (A2)
  • Clinicians should offer HCV screening at least annually to men who have sex with men (MSM) and to others who are not known to have HCV infection and:
    • Engage in receptive anal sex and other behaviors that may tear mucous membranes (A2)
    • Have multiple sex partners (A2)
    • Engage in sex while using recreational mind-altering substances, particularly methamphetamine (A2)
    • Have been diagnosed with another sexually transmitted infection (STI) within the previous 12 months (A2)
  • Clinicians should perform HCV screening for individuals who are not known to have HCV infection and have a possible exposure in a healthcare setting, including those who:
    • Have a break in the skin caused by a sharp object that is contaminated with blood, visibly bloody fluid, or other potentially infectious material or that has been in the source patient’s blood vessel (A2)
    • Have been bitten by an individual with visible bleeding in the mouth that causes bleeding in the exposed worker (A2)
    • Have been splashed on a mucosal surface with blood, visibly bloody fluid, or other potentially infectious material (A2)
    • Have non-intact skin (e.g., dermatitis, chapped skin, abrasion, or open wound) that has been exposed to blood, visibly bloody fluid, or other potentially infectious material (A2)

In the United States, an estimated 60% of chronic HCV infections result from use of shared needles, syringes, or other drug-use paraphernalia [CDC 1998]. Overall, sexual transmission accounts for approximately 5% of HCV infections, although transmission rates differ in select groups, as discussed below. Vertical transmission (transmission from mother to child) accounts for 5% to 6% of infection; receipt of contaminated organs or blood component transfusions before HCV testing of the blood supply began in 1992 accounts for approximately 5% of HCV infections [CDC 1998]. The average incidence of anti-HCV seroconversion after unintentional needle sticks or sharps exposures from a source with confirmed HCV infection is estimated at 1.8% [CDC 1998], and HCV infection has also resulted from unsterile skin piercing activities, such as tattoos in prisons (1%) [Alter 1999]. There are a few case reports that might suggest transmission during trauma, including biting [Dusheiko et al. 1990] and fist fighting [Bourliere et al. 2000], when there is potential for blood-to-blood transmission, but there are insufficient data to limit patients with HCV from participating in sports such as boxing or wrestling at this time.

Injection drug use: Sharing of injection drug use (IDU) equipment is an efficient method of transmitting HCV. In the United States, a reduction in new HCV infections between 1992 and 2009 was attributed to expansions of syringe-access programs, safer injection practices among people who inject drugs (PWID), and increased enrollment in drug treatment programs [Klevens et al. 2012]. However, HCV prevalence among PWID entering substance use treatment in New York City (n = 1,535) was 67% (95% confidence interval: 66% to 70%) during the 2006 to 2013 period and was not significantly different from that observed from 2000 to 2001 [Jordan et al. 2015].

The demographics of IDU now include many young people living in suburban and rural regions [Klevens et al. 2012]. Adolescents and young adults may advance to IDU after first becoming addicted to prescription oral opioids [Mateu-Gelabert et al. 2015]. Reports from several states (including New York State), underscore the importance of awareness of HCV risk among adolescent and young adult patients and of offering HCV screening to this population [CDC 2008, 2011a, 2011b, 2012; Zibbell et al. 2015; Pollini et al. 2011].

KEY POINTS: HCV SCREENING IN ADOLESCENTS AND YOUNG ADULTS
  • Epidemics of HCV infection that parallel opioid-use epidemics have been observed among young male and female injection drug users, primarily in suburban and rural areas [CDC 2008, 2011a, 2011b, 2012; Zibbell et al. 2015; Pollini et al. 2011].
  • HCV screening should be offered to at-risk adolescents and young adults.
  • In 2015, 2,309 (27.2%) of HCV cases reported in New York State (excluding New York City) were in people <30 years of age [NYSDOH 2016]. Among those <30 for whom risk information is available, 91% reported a history of IDU.

Intranasal drug use: In a systematic review of 28 studies on the prevalence of HCV in noninjecting drug users who smoked, sniffed, or snorted such drugs as heroin, powder or crack cocaine, or methamphetamine, investigators found HCV prevalence rates ranging from 2.3% to 35.3% [Stern et al. 2008; Scheinmann et al. 2007]. Among noninjecting drug users, sharing of oral and nasal drug use equipment is associated with an increased risk of HCV infection [Macias et al. 2008; Koblin et al. 2003; Neaigus et al. 2007]. In addition, blood and HCV RNA have been confirmed in the nasal secretions and drug-sniffing paraphernalia of intranasal drug users with HCV infection [Aaron et al. 2008].

Sexual transmission: Because many with HCV infection have a history of drug use, estimation of sexual transmission is a challenge (as reviewed in [Tohme and Holmberg 2010]). Sexual transmission of HCV among monogamous heterosexual couples is infrequent. The estimated maximum prevalence of HCV infection among sex partners of individuals with chronic HCV infection was only 1.2%, and the maximum incidence of HCV transmission through sex contact was 0.07% per year or approximately 1 per 190,000 sexual contacts [Terrault et al. 2013]. Sexual transmission risk increases in the setting of multiple partners, STIs, HIV, and exposure to blood [Tohme and Holmberg 2010]. Several reports have demonstrated isolated outbreaks of sexual HCV transmission among MSM with HIV infection who engage in receptive anal intercourse [CDC 2011b; Urbanus et al. 2009; van de Laar et al. 2009; Wandeler et al. 2012]. In a report from New York City on sexual transmission among MSM with HIV and no previous history of injection drug use, new HCV infections were highly correlated with receptive anal intercourse, engaging in sex while using methamphetamine, or participating in group sex [CDC 2011b].

History of incarceration: Incarcerated populations are a significant but declining portion of the HCV epidemic in the United States [Varan et al. 2014; Larney et al. 2013; Alvarez et al. 2014]. A study from 2009 to 2013 at two maximum-security prisons in New York State estimated an HCV prevalence of 10.1%; injection drug use, being the partner of a PWID, and HIV diagnosis were most strongly associated with HCV infection [Alvarez et al. 2014]. In 2015, 22.2% of newly reported cases of chronic or acute HCV infection in New York State (excluding New York City) had a reported history of incarceration [NYSDOH 2016]. In New York City, the rate of newly reported chronic HCV infection in 2015 was 86.3 per 100,000. In the incarcerated population of the city, the rate was 964.3 per 100,000 for the same year [NYCDHMH 2015].

Exposure to blood in a healthcare setting: The average incidence of anti-HCV seroconversion after unintentional needle sticks or sharps exposures from a source with HCV infection is 1.8% [CDC 1998]. Healthcare-related transmission of HCV is documented infrequently in the United States [Henderson 2003; Tomkins et al. 2012]. In 2014, among reported acute HCV cases that included information on exposure type, 1% was considered to be occupationally acquired [CDC 2017b].

Hemodialysis: The estimated 8% prevalence of anti-HCV antibodies among chronic hemodialysis patients is significantly higher than the estimated 1.6% prevalence in the general U.S. population [CDC 1998]. Nationally, 36 cases of acute HCV infection in 19 different hemodialysis clinics in 8 states were reported between 2014 and 2015, with epidemiologic and viral sequencing confirming transmission between patients [CDC 2016]. The Centers for Disease Control and Prevention (CDC) recommend HCV antibody screening upon admission for chronic hemodialysis patients, followed by screening every 6 months thereafter [CDC 2016, 2017a]. The National Kidney Foundation stratifies by prevalence and recommends antibody screening upon admission to facilities with a low HCV prevalence and consideration of HCV RNA testing upon admission to facilities with high HCV prevalence [KDIGO 2008].

Receipt of blood transfusion or organ transplant before 1992 or clotting factor concentrates from human plasma before 1987: Donor screening for HCV infection and inactivation procedures for pooled plasma and plasma derivative products have virtually eliminated the risk of HCV transmission through blood products in the United States [CDC 1998; Watson et al. 1992].

Vertical transmission: A 2011 meta-analysis estimated that the risk of vertical HCV infection to children of HCV antibody-reactive and HCV RNA detectable women was 5.8% for children of women without HIV and 10.8% for children of women with HIV [Arshad et al. 2011]. From 2011 to 2014, the national rate of HCV infection among women of childbearing age (15-44 years old) increased by 22% (from 139 to 169 per 100,000), and the national rate of infants born to women diagnosed with HCV infection increased by 68% (from 0.19% to 0.32%) [Koneru et al. 2016]. Factors associated with an increased risk of perinatal transmission include HIV coinfection and higher maternal HCV viral loads [Arshad et al. 2011; Benova et al. 2014]. Neither delivery by cesarean-section nor refraining from breastfeeding has been demonstrated to reduce vertical transmission [Koneru et al. 2016].

Tattoos, piercings, or acupuncture obtained in nonsterile settings: Tattoos or piercings obtained in nonsterile settings, and especially those obtained during incarceration, have been associated with HCV infection, even after controlling for injection drug use and transfusion before 1992 [Carney et al. 2013; Tohme et al. 2012]. Low levels of HCV RNA have been detected on acupuncture needles from individuals known to have HCV infection [Lemos et al. 2014], although acupuncture has not been established as a confirmed route of transmission.

HIV infection: HCV infection is common among persons with HIV because the routes of acquisition are similar. For decades, injection drug use has been recognized as the main risk factor for HIV/HCV coinfection, but an increasing number of sexually transmitted HCV infections have been documented in MSM with HIV [Hagan et al. 2015; Fierer and Factor 2015; Breskin et al. 2015]. In a recent study among MSM with HIV in Europe, Australia, and Canada, HCV incidence significantly increased from 1990 to 2014 [van de Laar et al. 2009]. Analyses of data from the Multicenter AIDS Cohort Study (MACS) in the United States and from a cohort of MSM with HIV in San Diego demonstrated a similar rise in HCV incidence among MSM [Witt et al. 2013; Chaillon et al. 2017]. In this population, sexual acts that may tear mucous membranes, sex while using methamphetamines, and having other STIs have been associated with HCV infection [Hagan et al. 2015; Fierer and Factor 2015].

Unexplained liver disease or abnormal transaminase levels: In primary care patients with an alanine transaminase (ALT) level 50 to 100 IU/L, HCV prevalence is 10-fold higher than in the general population, whereas hepatitis B (HBV) prevalence was not increased [Helsper et al. 2012].

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