ID specialists ponder universal HCV screening

As the rate of infection with hepatitis C virus soars in the United States, clinicians are thinking beyond high-risk patients and considering universal screening in the general population to get more people into care.

The dialogue accompanies recent reports about the increased prevalence of the virus, including one released by the CDC in May announcing a nearly threefold jump in reported infections over 5 years. Specifically, 850 HCV infections were reported to the CDC in 2010, and 2,436 were reported in 2015. But the agency cautioned that cases were underreported and estimated that, in fact, the actual number of HCV infections in 2015 may have reached as high as 34,000.

Source: UAB at Birmingham

The increase is driven by people who inject drugs (PWID), the CDC says, but a clear majority of HCV cases are still diagnosed in baby boomers. Adults born between 1945 and 1965 are six times more likely to be infected with HCV than people in other age groups, and they make up about 75% of all cases in the U.S. For those reasons, the CDC in 2012 recommended screening of all baby boomers.

However, given HCV’s wide reach in the country, an expansion of testing beyond this age cohort would be beneficial, according to Vincent Lo Re, MD, an associate professor of infectious diseases at the University of Pennsylvania Perelman School of Medicine.

“Society would benefit from any measure that sheds light on the subclinical burden of chronic HCV infection,” Lo Re said. “Earlier detection of chronic HCV could allow earlier treatment and cure, which would reduce rates of liver complications such as decompensated cirrhosis and hepatocellular carcinoma, decrease extra hepatic complications and help reduce HCV transmission and incidence of infection.”

Infectious Disease News spoke with several experts about the challenges of universal screening, including its cost and feasibility, and how these challenges might be overcome to improve the detection of HCV and increase patients’ access to treatment and, ultimately, a cure.

Is it feasible?

The relative ease or difficulty of screening for HCV depends partly on the population. Alfred DeMaria Jr., MD, medical director of the William A. Hinton State Laboratory Institute Bureau of Infectious Disease Prevention, Response and Services at the Massachusetts Department of Public Health, offered some examples.

“Universal testing is feasible now,” DeMaria said. “Now, will it actually happen? Any success we have seen among baby boomers is largely because they have regular medical appointments. With younger individuals or PWID, now you have a group of people who are at risk and don’t have regular medical appointments. It is a function of how people interact with the health care system.”

Although screening has been cost-effective in baby boomers who have been treated, the potential benefit in PWID and other less predictable populations is unclear, DeMaria added. PWID, he said, are also at high risk for reinfection even after initial cure.

Regardless of their perceived risk status, Michael S. Saag, MD, associate dean for global health and director of the Center for AIDS Research at the University of Alabama at Birmingham, argued that all patients should be screened.

“Hepatitis C screening should be universal, period,” Saag insisted. “The notion of selective screening in those at ‘higher risk’ assumes that those who are not in the high-risk groups are somehow OK. In fact, they are at the same risk of disease progression and injury to their livers as those who are in the high-risk group.”

Saag said the benefits of detecting and treating HCV cases make it worthwhile to broaden the search to all patients.

“We have an infection that can be cured,” he said. “I think we tend to get lost in the weeds of the [low] probability of a positive test in a lower risk population. But finding the individuals who are infected does not cost all that much. It’s a simple blood test done once for the majority of people. And for those we find who are infected, it can be life-changing. So why not?”

However, Saag acknowledged that there are additional costs associated with a positive test.

“The cost in time is related to those who test positive,” he said. “That implies that the providers, if they are going to order a test, need to have a plan for what to do with a positive result both in terms of follow-up — are they going to treat the patients themselves for HCV or refer them outside? — and for counseling the patients on what a positive test means.”

‘Insufficient’ progress

The argument for universal HCV screening must take into account the serious challenges of identifying infections among the population for which testing is currently recommended. Although screening has increased since 2013, Lo Re said, data as of June suggest that less than 20% of baby boomers had been screened by primary care physicians.

Eugene R. Schiff, MD, a professor of medicine and director of the Schiff Center for Liver Diseases at the University of Miami’s Miller School of Medicine, was blunt about results thus far.

“We are doing an insufficient job,” he said. “Unfortunately, screening of the baby boomers, where all the focus was, has failed.”

Schiff explained that family practitioners do not have the time to test patients for HCV, then contact them for follow-up visits. Costs of treatment are another concern as Medicaid restrictions frequently apply to baby boomers, although that burden has been alleviated somewhat, he said.

“The cost is getting a little better because there are multiple companies making equally effective [direct-acting antiviral (DAA)] therapies,” Schiff said. “A few class action suits have taken place involving people who weren’t given drugs because they weren’t sick enough. But we still can’t categorize this as progress.”

Schiff suggested that clinicians may also have difficulty getting reimbursed.

“To single these patients out and do all of this extra care, are they really being covered?” he asked. “If you take an insurer who is going to follow someone for life like the VA or Kaiser Permanente, then patients are receiving adequate care. But let’s say it’s someone who has insurance, and the insurers are saying they will follow them for 3 years, and they can go somewhere else after that.”

Lo Re said additional studies are needed to assess the progress made among baby boomers before HCV testing is extended to other populations.

“Before universal HCV screening could be recommended, more data are needed on the impact of current birth cohort screening and the cost-effectiveness of any universal HCV testing recommendation,” he explained. “Given that birth cohort screening has only recently been implemented, a full understanding of the impact of this recommendation has not yet been determined.”

Recently, researchers reported in MMWR that HCV testing among baby boomers increased more than 50% in New York following the implementation of a 2014 testing law that required health care providers to offer HCV screening to all patients born between 1945 to 1965. The percentage of patients with newly diagnosed HCV who were linked to care increased by 39.8% (from 24.1% to 33.7%) in New York and by 11.2% (from 19.5% to 21.7%) in New York City in 2014, compared with rates in 2011 and 2013.

However, even if screening among baby boomers does improve nationwide, more elusive populations like PWID remain.

To help reach those people, the CDC launched the Hepatitis Testing and Linkage to Care (HepTLC) initiative from 2012 to 2014. Since 2013, the CDC has recommended that clinicians conduct two HCV tests — one for HCV antibodies and the other for HCV RNA. A positive antibody test may merely indicate a resolved HCV infection or yield a biologic false-positive result, so following up with the RNA test can be used to confirm current infection.

In a study published in May 2016, researchers evaluated HepTLC to show where there might be gaps in the screening-to-treatment process. They assessed data from PWID-targeted screening of more than 15,000 people in nine cities throughout the U.S.

In all, 3,495 PWID (22.9%) tested positive for HCV antibodies. Of those patients, 1,630 (46.6%) were additionally tested for HCV RNA, and 1,244 (76.3%) tested positive. Among PWID with positive HCV RNA results, 861 (69.2%) were referred to care, and 198 (22.9%) of those who were referred attended their first care appointment.

Recent data have also shown that, once screened for HCV, PWID can adhere to treatment — countering entrenched policies in the U.S. that deny HCV treatment coverage to this population. In September, during the International Symposium on Hepatitis Care in Substance Users in New York City, researcher Alain H. Litwin, MD, hepatitis C treatment network lead and attending physician at Montefiore Health System, presented findings from a study that included 150 patients with HCV who were enrolled in opiate agonist therapy in the Bronx, New York City. Patients were randomly assigned to either directly observed treatment, group medical visits or treatment as usual.

Overall, 96% of the PWID had no detectable HCV at the end of their treatment courses, and 94% achieved SVR after 12 weeks of treatment.

“We actually found in rigorous fashion that drug use — whether it was prior to treatment, at baseline, right before treatment or during treatment — was not associated with adherence or cure,” Litwin told Infectious Disease News after his presentation. “So [drug use] is not a good reason to deny treatment.”

Areas of opportunity

According to researchers, EDs are a prime setting for screening all visitors.

A study published in June 2016 assessed an opt-out screening program for HIV, hepatitis B virus and HCV at an ED in Dublin, Ireland, from March 2014 to January 2015.

In all, 8,839 blood samples were analyzed. Of those, 447 (5.05%) tested positive for HCV. Fifty-eight (0.66%) of the positive HCV tests were new diagnoses. The prevalence rate of HCV was 50.5 per 1,000 patients, and the new diagnosis rate was 6.5 per 1,000 patients.

Programs like the one in Dublin are a way to screen people who do not have health insurance, Saag said.

“It’s unlikely that we’re going to get patients who don’t have primary care providers to get to clinics in the first place,” he said. “Rather, the way people who are not engaged in primary care seek medical attention is through EDs. Therefore, we should be screening all people who come to the ED for HCV as part of their routine care. We’ve been doing that at UAB Hospital for the past 2 and a half years, and we’ve had surprising results.”

Specifically, 11% to 12% of baby boomers who did not know their HCV status were diagnosed at UAB Hospital, he explained. Approximately 3% of the patients had insurance, and 18% were uninsured or underinsured.

“Finally, [among] those who were not in the baby boomer generation — in particular, those between the ages of 20 and 29 years — the [HCV infection] rates were up to 5%, and the majority of these individuals were exposed through IV drug use,” he continued. “So, the point is EDs are a key opportunity for us to screen for HCV and link those individuals to care.”

According to the results of a recent pilot study, most patients who received an offer for HCV screening during outpatient endoscopy accepted and completed the test the same day or same week. Robert Wong, MD, MS, director of research and education in the division of gastroenterology and hepatology at Alameda Health System’s Highland Hospital and assistant clinical professor of medicine at the University of California, San Francisco, said that incorporating HCV screening into outpatient endoscopy units “may provide a feasible option to achieve improved screening rates.” However, he cautioned that although the findings are “encouraging among safety-net populations, they may not be completely generalizable to more vulnerable populations with significant barriers in access to care.”

Correctional facilities represent yet another setting that can be exploited for HCV screening.

In a study published early this year, researchers assessed HCV prevalence among 10,790 inmates screened for the virus in the New York City correctional system. Of those inmates, 2,221 (20.6%) tested positive for HCV antibodies. Positivity was associated most with injection drug use (adjusted OR = 35).

“CDC estimates put the prevalence of chronic HCV in jails and prisons between 12% and 35%,” Lo Re said. “The success of the HCV elimination effort may well depend on reaching imprisoned patients, more than 90% of whom re-enter the general population.”

Back to the clinic

Although targeted HCV screening in a variety of settings has proven effective, experts say that any effort to expand screening must include primary care providers.

“Universal screening and treatment programs would definitely require more education of primary care providers, nurse practitioners and physician assistants to treat the uncomplicated cases of HCV,” Douglas T. Dieterich, MD, director of the Institute of Liver Medicine and professor of medicine at the Icahn School of Medicine at Mount Sinai, told Infectious Disease News. “There are many initiatives already ongoing to educate more physicians to screen and treat. I believe it’s certainly possible that we have the capability to treat new cases as they are discovered.”

Educating the public about screening and treatment could also be an effective approach, DeMaria said, but the message thus far has fallen short, even with advertisements for DAAs touting curative HCV therapies.

“Neither patients nor providers are primed to pay attention to messages about screening,” he explained. “Many people are unaware that they might have HCV. The message hasn’t permeated the public yet.”

Saag said ID clinicians have a responsibility to educate other providers about the benefits of HCV screening.

“The first approach is just to inform them of the benefits of testing and use a more general approach,” he said. “If you want to do a good job in terms of modern screening for disorders, this is a test you should be ordering at least once for all patients. Unfortunately, that doesn’t lead to 100% implementation.”

To ensure that providers fully comply with testing, Saag and Schiff both suggested offering incentives.

“What’s ultimately helped compel people to do this is to provide financial incentives to do the testing or, in some cases, financial disincentives for not doing the testing, and I think that would ultimately bring it around,” Saag said. “What I think we all kind of lose here is this notion that we have an infectious disease that is curable, and failure to cure that infection will lead to individuals developing progressive liver fibrosis and a fair number of overt cirrhosis cases. We can prevent that if we are just more proactive.”

He added that the potential effects of universal HCV testing extend well beyond individual patients.

“Not only is there the benefit to the individual, but there is a benefit to society,” Saag said. “By testing and treating everyone with HCV, we could establish an aspirational goal of eradicating HCV.” – by Joe Green and Rob Volansky

Editor’s note: A version of this article appeared in HCV Next.

• References:
• Akiyama MJ, et al. Public Health Rep. 2017;doi:10.1177/0033354916679367.
• Blackburn NA, et al. Public Health Rep. 2017;doi:10.1177/00333549161310S214.
• Campbell B, et al. Clin Gastroenterol Hepatol. 2017;doi:10.1016/j.cgh.2017.09.047.
• CDC. New Hepatitis C Infections Nearly Tripled Over Five Years. www.cdc.gov/nchhstp/newsroom/2017/Hepatitis-Surveillance-Press-Release.html. 2017. Accessed October. 17, 2017.
• CDC. People Born 1945-1965 (Baby Boomers). www.cdc.gov/hepatitis/populations/1945-1965.htm. 2017. Accessed October 17, 2017.
• Flanigan CA, et al. MMWR Morb Mortal Wkly Rep. 2017;66:1023-1026.
• Litwin AH, et al. The PREVAIL Study: Intensive Models of HCV Care for People Who Inject Drugs. Presented at: International Symposium on Hepatitis Care in Substance Users. Sept. 6-8, 2017, New York.
• O’Connell S, et al. PLoS One. 2017;doi:10.1371/journal.pone.0150546.

• For more information:
• Alfred DeMaria Jr., MD, can be reached at 305 South Street, Jamaica Plain, MA 02130; email: Alfred.demaria@state.ma.us.
• Douglas T. Dieterich, MD, can be reached at 17 E. 102nd St., New York, NY 10029; email: douglas.dieterich@mountsinai.org.
• Vincent Lo Re, MD, can be reached at 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104; email: Johanna.Harvey@uphs.upenn.edu.
• Michael S. Saag, MD, can be reached at 1720 2nd Ave. Birmingham, AL 35294; email: jandereck@pcipr.com.
• Eugene R. Schiff, MD, can be reached at Jackson Medical Towers, 1500 NW 12 Ave., Suite 1101 ET, Miami, FL 33136; email: lworley2@med.miami.edu.

Disclosures: DeMaria reports no relevant financial disclosures. Dieterich reports associations with Achillion Pharmaceuticals, Boehringer Ingelheim, Gilead Sciences, Idenix Pharmaceuticals, Janssen, Merck and Vertex. Lo Re reports receiving grant support from the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Institute of General Medical Sciences and AstraZeneca, all to the University of Pennsylvania. Saag reports receiving grant support from, and serving as a consultant or advisor to, Bristol-Myers Squibb, Gilead Sciences, Merck, Proteus and ViiV Healthcare. Schiff reports serving as a consultatnt for Acorda; serving on the advisory board of Bristol-Myers Squibb, Gilead Sciences, Merck and Janssen; serving on the data monitoring board for Arrowhead, Bristol-Myers Squibb, Pfizer and Salix; and receiving grant support from Abbott, Beckman Coulter, Bristol-Myers Squibb, Conatus, Discovery Life Sciences, Gilead Sciences, Janssen, MedMira, Merck, Orasure Technologies, Roche Molecular and Siemens.