COMMENTARY

The Time to Eradicate Hepatitis C Is Now

William F. Balistreri, MD

Disclosures

March 17, 2020

It is becoming easier to imagine a world without hepatitis C, thanks to direct-acting antivirals (DAAs) that result in cure rates of over 95% across all genotypes after only 8-12 weeks of oral administration.

Dr Harvey J. Alter, the pioneering virologist whose work led to the discovery of hepatitis C virus (HCV), indulged this very same thought in a 2019 lecture. He noted that the concept that HCV "might be eradicated even in the absence of a vaccine" is no longer a fantasy. Yet, he was also clear that making this a reality would require some arduous steps, beginning largely with the implementation of robust screening efforts to identify asymptomatic individuals who may not know they have HCV.

That reality is now here. The US Preventive Services Task Force (USPSTF) recently recommended that "all adults aged 18 to 79 years be screened for HCV infection," a major change from their 2013 guidelines recommending limited screening of high-risk individuals and baby boomers. This updated strategy is in response to the efficacy and safety of DAAs, combined with emerging evidence that the HCV epidemic, paralleling the rise in opioid use, has broadened to envelop younger age groups.

The Centers for Disease Control and Prevention has also proposed "at least once in a lifetime hepatitis C screening for all adults aged 18 years and older." Similarly, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America conjointly released updated recommendations for "one-time, routine, opt-out HCV screening for all individuals aged 18 years or older."

It should be noted, however, that recommendations from other organizations are currently more limited. The American College of Gastroenterology recommends screening for HCV infection in higher-risk patients. The American College of Obstetricians and Gynecologists recommend offering HCV screening to pregnant women with risk factors.

These more wide-ranging screening recommendations come in response to an increasing prevalence of viremic HCV infection in the United States. According to data from the National Health and Nutrition Examination Survey, approximately 1.9 million US adults were HCV viremic from 2011 to 2016; however, only 50% are aware of their HCV infection. Approximately one third of persons aged 18-30 years who inject drugs are infected with HCV, a rate that climbs to 70%-90% among older persons (ie, > 30 years) in this category. HCV prevalence also doubled in women aged 15-44 years from 2006 to 2014.

Learning From Successful Screening Examples

To be successful, enhanced screening strategies must be adopted with primary care providers and other key stakeholders in mind. This includes efforts to emphasize the impact and value of streamlining HCV care in community settings and overcoming access to treatment barriers. Beyond simply increasing the rates of cure, this would also enhance patient-reported outcomes and other clinically important outcomes (eg, cardiovascular disease). The clinical impact and cost-effectiveness of delivering such value-based healthcare strategies have also been emphasized.

The question of how we get there is more complicated. Universal screening will amplify the challenges we originally encountered with high-risk groups, particularly the newly added cohort of those aged 19-55 years, who often get less consistent primary care. Screening success is also impossible to achieve without linkage to care.

One encouraging example, however, is found in the Appalachian region of the United States, which leads the nation in new cases of HCV infection. Most new cases occur in rural Kentucky counties with underserved populations, where access to HCV treatment specialists is limited. Primary care providers in these areas have expressed a desire to learn HCV care navigation from diagnosis to cure. In response, the Kentucky Hepatitis Academic Mentorship Program (KHAMP) was developed through multidisciplinary collaboration to increase the number of HCV-infected people receiving screening and curative therapy through their local provider.KHAMP also works in collaboration with the state Medicaid program to help obtain insurance coverage for DAA therapy. This ensures that KHAMP participants will no longer be required to consult with a specialist in order to prescribe HCV treatment.

International examples of successful screening programs are also worth noting. The country of Georgia embarked on a successful HCV elimination program, constructing an HCV care cascade.In less than 3 years, 40% of the Georgian adult population underwent screening with a rapid HCV test at venues throughout the country. Other cost-effectiveness and cost-benefit analyses of screening and decentralized care were performed in Bulgaria; the state of Punjab, India; and Egypt, which has the highest prevalence of HCV infection in the world.The level and rate of turnout, cost, and other logistical issues described by these programs provide essential information for effective planning, design, and evaluation methods for larger national mass screening and treatment programs.

Implementing New Screening Guidelines in Primary Care

Elimination of HCV infection will require the engagement of frontline healthcare practitioners, without whom we cannot increase the capacity to treat patients.

Easy-to-use, effective, and safe point-of-care (POC) decision tools must be created for the management and treatment of HCV infection. These should provide guidance regarding test interpretation, initiation of DAA therapy, and management of uncomplicated cases of HCV. They should also help practitioners recognize and manage patients with advanced disease due to HCV who require additional subspecialty care.

One proposed algorithm begins with universal HCV screening and diagnosis by testing for HCV antibody with reflex testing (same sample) to detect HCV RNA. The suggested pretreatment evaluation uses platelet-based stratification to initially assess fibrosis. Pan-genotypic regimens are recommended for treatment. Unless clinically indicated, on-treatment monitoring is optional. Confirmation of cure (undetectable HCV RNA post-treatment) is followed by harm-reduction measures, as well as surveillance for hepatocellular carcinoma in patients with advanced fibrosis or cirrhosis.

Such simple, effective algorithms must be flexible and scalable, depending on the target population, available funding and facilities, and the speed with which results are needed.

Where Could Screening Be Conducted?

Multiple opportunities exist for screening: routine health checks, emergency department (ED) visits, prenatal care or well-child visits, and needle-syringe exchange sites.

In a universal opt-out HCV screening program conducted in two EDs in San Diego, HCV antibody tests were conducted in 905 individuals over a 1-month period.They detected a seropositivity rate of 10%, with 51% viremic (3.4% of all participants) and 42% linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by more than sevenfold, underlining the importance of HCV screening.

Calner and colleagues compared the rates of HCV identification, linkage to care, and treatment success between different study sites at one medical center.The program used a best practice advisory to prompt testing. Overall, 28,435 patients were screened across five clinical locations: the ED, the inpatient service, and three different clinics (general internal medicine, infectious disease, and family medicine). The rates of HCV RNA positivity ranged from 2% to 15%, and the rates of linkage to care varied from 18% to 76%.

Studies have also looked into expanding the venues at which accurate screening results can be obtained. POC testing in community settings has been shown to be effective in reaching at-risk populations and facilitating diagnosis. Home blood self-sampling may prove to be a useful tool for screening and epidemiologic studies. Dried blood spot testing was conducted in 20 community pharmacies, with a resulting cost-effectiveness below commonly accepted thresholds.

Further Expansion of Whom We Test

The USPSTF's recommendations note that "clinicians may also need to screen high-risk individuals younger than 18 and older than 79 years, especially injection drug users."In my opinion, children and adolescents may be a key target demographic, because multiple DAA regimens are now approved for children aged 3-17 years.

Children born to women with HCV. The recent AASLD recommendations state that all children born to women with acute or chronic HCV should be tested for HCV infection. Kentucky's new state law requiring all pregnant women be tested for HCV also recommends testing for children born from a pregnant woman who has a positive HCV test result. One in 56 Kentucky births are to mothers who have HCV, and approximately 1700 infected infants are born annually to 29,000 HCV-infected mothers. Despite the high prevalence of HCV, rates of maternal and infant screening remain suboptimal. Bell and colleagues reported that the HCV screening rate for mothers of infants with in utero opiate exposure increased from 58% in 2013 to 90% in 2018. Of the mothers tested, 48% were HCV positive and 53% of the infants were tested for HCV, with 7.4% being HCV positive.

Adolescent substance abuse. Because substance use is probably underdiagnosed in adolescents, expanded universal HCV testing programs or more prospective cohort studies will be needed to evaluate the true burden of disease in this population. However, in one study, Fernandes and colleagues determined a 5% seroprevalence rate of HCV infection using POC testing of adolescents admitted to a drug rehabilitation center; 100% of all HCV-positive individuals reported the use of heroin, versus only 11% of HCV-negative individuals.In another study, Epstein and colleagues assessed over 269,000 youths aged 13-21 years who visited a qualified health center at least once from 2012 to 2017, reporting that only 2.5% were tested for HCV, of whom 1.8% were anti-HCV positive. Of the participants with documented cocaine, opioid, or amphetamine use, only 30% were tested and 7.1% were anti-HCV positive. Approximately 75% of the seropositive patients underwent HCV RNA testing, of whom 45% were found to be viremic.

Moving One Step Closer to Eradication

In 2020, the focus on HCV has shifted from the discovery of safe and effective antivirals to eradication via comprehensive screening, staging, and treatment.

The elimination of HCV in the United States is at hand, but it will require commitment at both a community level (primary care practices) and a federal level. Policies and payment systems must be enhanced to address barriers, allowing for widespread instillation of best practice alerts in electronic medical records, seamless reflex HCV RNA testing, and ready access to specialists (including teleconsultation).

The role of primary care practitioners will change too, moving toward a more decentralized model of care. This will require that they treat patients with HCV rather than performing staging and requesting consultation with a hepatologist or an infectious disease specialist. Financial and regulatory incentives (quality improvement metrics) must be in place to ensure prioritization of HCV screening and management strategies in the face of competing practice demands.

By marshaling these collective efforts, we may move one step closer to eradicating HCV.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, Liver Transplantation; and professor, University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center. He has served as director of the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's for 25 years, and frequently covers gastroenterology, liver, and nutrition-related topics for Medscape. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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