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Facing the Challenges of Universal Screening for HCV

By most objective measures, implementing universal screening in baby boomers has been suboptimal. In the estimation of many experts, it has been a failure. This failure is frustrating because the end zone — eradication of HCV altogether — feels tangible in the DAA era. But despite the setbacks, talk of universal screening for HCV persists.

Vincent Lo Re, MD, MSCE, associate professor of Infectious Diseases in the Perelman School of Medicine at the University of Pennsylvania, provided a broad view. “Society would benefit from any measure that sheds light on the subclinical burden of chronic HCV infection,” he said. “Earlier detection of chronic HCV could allow earlier treatment of chronic HCV and cure, which would reduce rates of liver complications such as decompensated cirrhosis and hepatocellular carcinoma, decrease extra-hepatic complications, and help to reduce HCV transmission and incidence of infection.”

There will be challenges. With a shortage of hepatologists, PCPs and other providers need to be up to speed on HCV screening procedures, if they can find the time to do it. They also must treat. HCV is currently miles away from the test-and-treat approach that rendered HIV manageable, largely because of the cost of therapies. High rates of HCV among unpredictable populations such as people who inject drugs (PWID) and prison inmates present a moving target.

“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 said. “Given that birth cohort screening has only recently been implemented, a full understanding of the impact of this recommendation has not yet been determined.”

Barbara J. Turner, MD, MSEd, MA, James D. and Ona I. Dye Professor of Medicine and director of the Center for Research to Advance Community Health (ReACH) at the University of Texas Health Science Center San Antonio, summed up the skepticism. “Universal screening for everyone in the U.S. is not reasonable because the prevalence of this disease is much lower in other age groups that are not baby boomers,” she said. “It has been a big problem operationalizing this guideline. There are no data at this point to support universal testing.”

Question of Feasibility

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 a balanced perspective on the possibility of universal screening. “Universal testing is feasible now,” he 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 who don’t have regular medical appointments. It is a function of how people interact with the health care system.”

For Turner, there are simply too many obstacles standing in the way of universal screening. “First, without coverage for screening, evaluation, and treatment, the costs are too great for low income persons to bear,” she said. Similarly, Medicaid restrictions could be prohibitive to treating all patients. “For now, the drug companies make these very expensive drugs available through a compassionate drug program if the patient meets low income criteria, but it is unclear how long these programs will last.”

Drawing parallels between screening baby boomers and universal screening may be difficult simply because of numbers, according to Turner. “Roughly 75% to 80% of HCV disease is in the baby boomer age group,” she said, noting that apart from the spike in infections among young opioid users, prevalence rates in most other demographics are low. Screening them might be a misuse of resources.

Lo Re acknowledged that screening increased since 2013, but recent data suggest that less than 20% of the boomer cohort has been screened by a PCP. “Chronic HCV infection may be missed under current risk-based and birth cohort screening guidelines,” he said.

DeMaria suggested that cost-effectiveness is at the heart of the discussion. “Does it provide an outcome that would be beneficial?” he said. “I can’t answer that. It is a question that needs to be studied.”

Despite the shortcomings, DeMaria believes that universal screening has been cost-effective in the baby boomers who have been screened and treated, but he suggested that it is unclear whether that would be the case in less predictable populations like PWID. “They are at a high risk for reinfection even if they have been treated and cured,” he said.

Awareness is another relevant issue, according to DeMaria. Television advertising of DAAs has shed light on the fact that curative therapies are available. “However, neither patients nor providers are primed to pay attention to messages about screening,” he said. “Many people are unaware that they might have HCV and not know it. The message hasn’t permeated the public yet.”

As for providers, DeMaria admitted that efforts to make PCPs aware that baby boomers should be screened have not been successful. However, the failures of universal screening in baby boomers may not predict a failure in overall universal screening. “It could go either way,” he said. “Certainly, there are issues to avoid. But if it is completely universal, then everyone has to do it, and there is no clinical decision-making involved. It might end up being successful.”

“Universal screening and treatment programs would definitely require more education of PCPs and NPs and PAs to treat the uncomplicated cases of hepatitis C,” Douglas T. Dieterich, MD, director of the Institute of Liver Medicine and professor of Medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, told HCV Next. “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.”

Test and Treat

It is worthwhile to look more deeply into the test and treat approach. “The most positive result to come from universal screening is that through treating persons who are diagnosed with chronic infection — both insured or uninsured — in programs that help defray the costs of screening, evaluation, and treatment, it is possible to successfully cure well over 90% of persons whose disease may have progressed to liver failure and liver cancer,” Turner said. She stressed that liver cancer is increasing in the U.S., and that treating would have clear benefits. “In our experience, patients diagnosed with chronic HCV infection through routine screening have been very grateful that this disease was found and they could be cured.”

Whether the personal benefits of test-and-treat would play out at the population level remains to be seen, according to DeMaria. “We don’t have evidence that testing people is cost-effective, but we do have evidence that treating people is cost-effective,” he said. “We haven’t come to the decision as a society about how to implement what seems to be a cost-effective approach to testing and treating people.”

A key factor is the amount of support required for patient follow-through, DeMaria said. “It is not just a matter of giving people a prescription for 12 weeks and saying good luck,” he said. “With HIV, there is a lot of support around case management. That infrastructure is not yet in place for HCV. Incomplete treatment of HCV is not good, so we don’t want to waste the money for the drugs to treat people. The investment has to be not just for treatment, but for treatment and support.”

DeMaria acknowledged that the U.S. is still far from this status.

Some experts have suggested that following the example set by Australia might help bring universal screening to fruition. Bargaining with pharma for unlimited use of drug for a finite period could ultimately save the system money and motivate patients to check their status. But currently, a program such as this feels far from reality.

Failure in Baby Boomers

Eugene R. Schiff, MD, professor of Medicine and director of the Schiff Center for Liver Diseases at the University of Miami Miller School of Medicine, offered a stark report on the screening effort in baby boomers. “We are doing an insufficient job,” he said. “Unfortunately, screening of the baby boomers, where all the focus was, has failed.”

The reasons for this failure are multifactorial, according to Schiff. One is that family practitioners simply do not have enough time in the clinic to test. Another is the two-step screening process. “You have to call them back again,” he said. “The next thing is that there are still barriers to treatment. There are still hurdles as far as access goes.”

Medicaid restrictions frequently apply in the 1945 to 1965 group, as well. “The cost aspect is getting a little better because there are multiple companies making equally effective DAA therapies,” Schiff said. “We still can’t characterize this as progress.”

Clinicians also face obstacles in terms of reimbursement. “To single these patients out and do all this extra care, are they really being covered?” Schiff said. “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, the insurers are saying they will follow them for 3 years and they can go somewhere else after.”

Schiff recommended “putting some teeth” into enforcement of recommendations to screen baby boomers. “You would have to say, look, if you’re not doing what is recommended by the CDC, you’re below standard of care,” he said. “Then, if they’re not standard of care, they don’t get coverage.”

Injection Drug Users

At the outset of the DAA era, Durham and colleagues suggested that the impact of DAAs could be hamstrung by poor screening and treatment rates. They developed a model based on epidemiological data of the U.S. for the years 1992 through 2014. The specific focus was injection drug use. They aimed to quantify the impact of DAAs at various screening and treatment rates. Results indicated that a fourfold increase in annual treatment from that time could prevent more than 250,000 HCV-associated deaths. They reported simultaneous increases in diagnosis and treatment capacity could bring the number of infections in the U.S. to near 300,000 infections by 2040. To reach complete elimination of HCV transmission in the U.S., nearly universal screening of PWIDs is required, along with an annual treatment rate of at least 30%, according to the researchers.

While it may seem like an easy solution to target PWID, Schiff said that that population presents a moving target for multiple reasons. “Injection used to be predominantly on the street in urban areas,” he said. “Now we are seeing it in rural areas. We’re seeing as many women as men, in addition to people on the street in urban areas. The demographics are changing.”

These patients should also go to rehab at some point, according to Schiff. “This is an additional cost,” he said.

The risk for reinfection is high in this group, as well. “This is where a vaccine would come into play, but we have not developed one yet,” Schiff said. “If there was a vaccine, we could treat the drug users, and then vaccinate them. Now we have to treat them and try to change their behavior in terms of addiction and sharing needles, which is a very difficult thing.”

Many experts believe that the natural place to tackle the HCV epidemic among opioid users is in the ED. “That’s a good place to start because that’s where these people are interacting with the health care system,” DeMaria said. “There is urgency and prioritization surrounding injection drug use. This could happen in the ED regardless of screening recommendations.”

O’Connell and colleagues conducted an opt-out screening program for HBV and HCV at an ED in Dublin, Ireland, from March 2014 to January 2015. Individuals who tested positive were linked to care. The analysis included 8,839 patient samples. Clinicians reached a sustained target uptake of more than 50% after the third week of the study. The HCV positivity rate was 5.05%, with 0.66% of those being new infections, for an overall rate of 6.5 per 1,000. The study rate was 50.5 per 1,000, according to the findings. “Opt-out blood borne viral screening was feasible and acceptable in an inner-city ED,” the researchers concluded.

“To reach younger men, we aim to test in the ED,” Dieterich said. “Obviously, not all men are taken to the ED, but we believe it’s a good place to start.”

The Prison System

Akiyama and colleagues aimed to assess predictors of HCV incidence in the New York City jail system. The study included 10,790 inmates screened between June 13, 2013, and June 13, 2014. The HCV antibody positivity rate in this cohort was 20.6%. Injection drug use was the strongest predictor of a positive test (adjusted OR = 35; 95% CI, 28.5-43). Women had a greater risk for infection compared with men (aOR = 1.3; 95% CI, 1.1-1.5), according to the findings. Other results showed that compared with non-Hispanic blacks, Hispanic individuals carried an increased risk for infection (aOR = 2.1; 95% CI, 1.8-2.4), as did non-Hispanic whites (aOR = 1.7; 95% CI, 1.5-2.1). A subset of inmates born after 1965 without HIV who reported not being PWID carried an HCV infection rate of 5.6%. Non-injection drug use predicted infection in this group, as did being non-Hispanic white, Hispanic, recidivist and homeless, according to the findings. “These data reveal differences in HCV infection by sex, race/ethnicity, and socioeconomics in a large jail population, suggesting that a focused public health intervention is required and that universal screening may be warranted,” the researchers concluded.

“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.”

This population can be characterized as “hard to reach,” according to Lo Re. “HCV cannot be eliminated without reaching these populations,” he said. “I would target people who actively use injection drugs, are in harm reduction programs, and are imprisoned for HCV screening.”

Other Health Care Providers

Turner and colleagues aimed to identify support needs of low income baby boomers recently diagnosed with chronic HCV infection. Results indicated that these individuals experienced psycho-emotional effects from stigma surrounding the disease, along with shame and fear. They required assistance in dealing with high-risk behaviors. These patients were concerned about infecting others and cognitive adverse events related to poor understanding of the disease. Importantly, the study shed light on access to care concerns that were largely related to the high cost of therapy. These patients also had difficulty with comorbidities of HCV and the care required to treat them.

Despite these obstacles, participants were strongly in favor of universal screening in the baby boomer birth cohort. “Nursing and other allied health personnel require structured support programs to assist older persons diagnosed with hepatitis C with addressing these common challenges with the ultimate goal of achieving a cure,” the researchers concluded.

Much of the burden will fall to PCPs because of a shortage of hepatologists, and this could be problematic, according to Turner. “Primary care practices have been slow to implement screening because it requires implementing an infrastructure to identify and test baby boomers and then counsel and evaluate them,” she said. She added that simply dealing with the paperwork for baby boomers has been costly and time-consuming for providers. “Unlike mammography and colon cancer screening, for example, there is no financial incentive for a primary care practice to do all of this because HCV screening does not yield a bonus from insurers.”

The next issue for Turner is that PCPs often have little training in the next steps to treatment. “They would rather not screen and then not know how to manage the disease,” she said. Telemedicine may help. “But few systems have been set up to make this feasible.”

That said, there may be reason for optimism, according to Turner. “Treatment in primary care practices appears to be just as successful as in liver specialty practices,” she said.

But there are practical considerations, DeMaria added. “I don’t think there’s any magic to recommending screening in primary care, but it may or may not happen,” he said. “If you did everything that’s recommended in a primary care visit, it could take up to 7 hours. In a 15-minute appointment, it’s hard to do all that.”

It is also worth noting that time must be taken to explain the epidemic to people who don’t perceive themselves to be at risk for HCV, according to DeMaria. “People are expecting a flu shot or to be sent for a mammogram or PAP test, but they may not be expecting an HCV test,” he said.

The Antenatal Setting

Aebi-Popp and colleagues suggested that a primary reason why routine antenatal screening is not recommended is because of few treatment options to prevent mother-to-child transmission of HCV during pregnancy or delivery. Moreover, women with HCV and their newborns are not linked to care as is the case with HIV. “Universal screening of HCV during pregnancy should urgently be re-evaluated in the light of the new DAAs,” the researchers wrote. “Balancing the benefits for the mother and child against additional costs for the health care system remains very important. With successful treatment of the mother, there is the potential for completely eliminating vertical HCV transmission.”

Waruingi and colleagues compared risk-based screening and universal screening in a cohort of 419 pregnant women at a high-risk inner city clinic from January 2012 to March 2012. Medical records showed that 8.8% of these women were at high risk for HCV infection. HCV antibody testing was performed in 95% of the low-risk group. Results showed an HCV prevalence of 3.18% (95% CI, 1.36-6.5) in all tested women, compared with a prevalence of 0.95% (95% CI, 0.31-2.59) in women who were selectively tested based on risk. A sensitivity of 0.85 (0.42-0.99) and a specificity of 0.52 (0.45-0.58) was reported for the screening questionnaire among all women who had HCV antibody testing and screening from the questionnaire. “Using a screening questionnaire to identify women at risk for HCV infection during pregnancy underestimates the real prevalence of HCV,” the researchers concluded. “A universal screening should be considered in high risk cities.”

“Patients in their 20s, 30s, and 40s tend to access health care less often than baby boomers, except for women going to their gynecologist,” Dieterich said. “That’s where we plan to target the younger female population.”

Looking Ahead

For DeMaria, one way forward is to reflect on past successes. “We are trying to develop an HCV-centered continuum of care like we have with HIV,” he said, and stressed consistent evaluation of data. “How many patients are successfully linked to care? How many get treated? How many who are treated reach SVR? Once we see how those numbers play out, we’ll know more.”

This research is underway, according to DeMaria. “As of now, the data are not as robust as with HIV,” he said. “There is not enough extended surveillance over the years. But hopefully we will get there.”

Lo Re summarized the obstacles to universal screening from the practitioners’ perspective. “Insufficient staff time, competing demands on providers’ attention, and providers’ unwillingness to inquire about HCV risk factors have been important barriers to birth cohort HCV screening,” he said. “Devising strategies to overcome these barriers will be important to overcoming them.”

Dieterich suggested keeping the big picture in mind. “The biggest advantage to universal screening would be the potential eradication of hepatitis C in the U.S.,” he said. “Early detection leads to early treatment, which means decreasing the spread of the virus, decreasing maternal infant transmission, and hope for eradicating the virus in the future.”

• References:
• Aebi-Popp K, et al. J Virus Erad. 2016;2:52-54.
• Akiyama MJ, et al. Public Health Rep. 2017;doi:10.1177/ 0033354916679367.
• Durham DP, et al. Clin Infect Dis. 2016;doi:10.1093/cid/civ894.
• O’Connell S, et al. PLoS One. 2016;doi:10.1371/journal.pone.0150546.
• Turner BJ, et al. J Clin Nurs. 2017;doi:10.1111/jocn. 13806.
• Waruingi W, et al. J Neonatal Perinatal Med. 2015; doi:10.3233/NPM-15915024.

• 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, MSCE, can be reached at 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104; email: Johanna.Harvey@uphs.upenn.edu.
• 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.
• Barbara J. Turner, MD, MSEd, MA, can be reached at 7411 John Smith Dr, Suite 1050 San Antonio, TX 78229; email: turner@uthscsa.edu.

Disclosures: DeMaria and Turner report 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 National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of General Medical Sciences, and AstraZeneca (for epidemiologic study of risk of infections and acute liver injury associated with anti-diabetic drugs), all to University of Pennsylvania; he reports no consulting. Schiff reports being a consultant with Acorda; being on the advisory board of Bristol-Myers Squibb, Gilead, Merck and Janssen; being on the data monitoring board of Arrowhead, Bristol-Myers Squibb, Pfizer and Salix; receiving grant support from Abbott, Beckman Coulter, Bristol- Myers Squibb, Conatus, Discovery Life Sciences, Gilead, Janssen, MedMira, Merck, Orasure Technologies, Roche Molecular and Siemens.