Making strides to stamp out HCV

The United States has seen significant progress in the battle against hepatitis C virus (HCV), most notably in the emergence over the past decade of highly effective, simplified treatments. However, new infections continue to rise across the country and access to care remains a major barrier to treating those at highest risk.

"We have these direct-acting antiviral medications approved in 2014 that are really safe and well tolerated, and we can cure over 95% of people who take them," said Emily Cartwright, MD, associate professor of medicine in the division of infectious diseases at Atlanta's Emory University School of Medicine. "The challenge in front of us is finding a way to get this treatment to more people."

The success of direct-acting antiviral therapy led the World Health Organization to set a goal in 2016 of eliminating viral hepatitis globally by 2030. Soon after, the National Academies of Science, Engineering, and Medicine set a target of reducing HCV infections by 90% in the United States by 2030.

In 2022, there were nearly 67,400 estimated acute HCV infections in the United States, a substantial increase over the 17,000 cases reported in 2011, according to the CDC's most recent Viral Hepatitis Report, published in April 2024. Although cases fell 6.3% between 2021 and 2022, the report said, rates of infection and HCV-related deaths remained disproportionately high among minority populations.

Similarly, data from the National Health and Nutrition Examination Survey (NHANES), published in the November 2023 Clinical Infectious Diseases, show higher rates of infection among low-income, un- and under-insured populations. The study also noted that of the more than 2 million adults with current HCV infections during 2017-2020, more than 30% were unaware they had the disease.

In addition, there is concern that NHANES data underestimates the true prevalence of HCV, according to Karla Thornton, MD, MPH, an infectious diseases subspecialist based at the University of New Mexico Health Sciences Center in Albuquerque. Modeling data she presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in November 2023 as a late-breaking abstract estimated that the prevalence of HCV in the U.S. in 2017-2020 was closer to 4 million when adjusted for underrepresentation of people who inject drugs.

Slowing HCV's spread must start with diagnosis, said Dr. Cartwright, who also directs the HCV program at the Atlanta Veterans Affairs (VA) health system and works on the Clinical Interventions Team in the CDC's division of viral hepatitis. Routine screening is especially important for a disease that's often asymptomatic in its early stages, she noted.

But reaching those at highest risk, mainly those who use injection drugs, remains a major challenge, said Dr. Cartwright and other experts.

"We can't attack hepatitis C without addressing the country's addiction drug crisis, especially among younger people who often don't seek out regular health care," said Alain Litwin, MD, MPH, vice chair of academic affairs and research at Prisma Health-Upstate in Greenville, S.C., whose research focuses on improving HCV care for those who use drugs and increasing access to treatment. "We have wonderful medications and cure rates but no coordinated, funded effort to link people to comprehensive care."

Incorporating routine screening

In 2020, the CDC began recommending universal one-time screening for adults ages 18 years or older and for all pregnant persons. Last summer, the agency issued updated guidance stating that testing, a two-step process involving an anti-HCV antibody test and a confirmatory polymerase chain reaction test, should be completed in a single visit.

"Some labs were having patients come back for a second blood draw to complete testing," said Dr. Cartwright, a corresponding author on the updated screening strategy. "But we've seen that about a third of patients don't come back, and doing both in a single visit significantly improves the number of people who complete testing."

Screening rates have gone up in recent years, driven in part by awareness of the effective treatment options, said infectious diseases subspecialist George Abraham, MD, MACP, an ACP Past President and a coauthor of ACP's best practice advice on HCV care, published Oct. 6, 2020, in Annals of Internal Medicine. He noted that testing is relatively inexpensive and easy to implement as part of a comprehensive exam in primary care, along with other common blood-based screening tests.

Still, HCV testing often falls by the wayside in a busy primary care office, he said, especially since it hasn't been prioritized by insurers.

"Agencies that hold insurers responsible for quality push hard on things like cancer screenings and diabetes [measuring hemoglobin A1c], but hepatitis C hasn't captured the same attention," he said. "That's had a trickle-down effect. Primary care physicians don't focus on it as much, and treatment is not always covered."

Historically, HCV testing was triggered by risk factors in a patient's history or an abnormal liver function test, he said. However, that strategy can miss patients who develop risk factors after testing, don't reveal risk behaviors, or don't request screening due to the stigma around HCV's association with drug use.

"Where you reasonably think someone might be at risk, order the blood test," said Dr. Abraham. "We could be saving a life in terms of preventing progress to chronic liver disease and cancer."

Raising awareness is one key to improving screening rates, since many people with the disease don't know they're infected, said Dr. Thornton.

Even more important is making tests available outside of the traditional primary care setting, added Dr. Thornton, who is also senior associate director of Project ECHO, a telementoring program that trains clinicians in rural and underserved areas to diagnose and treat HCV, as well as other disorders.

"We need more outreach to high-risk populations," she said. "Methadone clinics and other addiction treatment centers can incorporate hepatitis C testing into their programs so that people can get tested at the same time that they're getting treated for substance use disorder."

Treatment, simplified

Shifting HCV diagnosis and treatment to primary care is a critical strategy that can reduce the rate of transmission and minimize harm from HCV, said Dr. Litwin. Since the advent of highly effective, simplified treatment regimens, HCV no longer requires subspecialist intervention, he said.

Once patients are diagnosed and in care, treatment is relatively uncomplicated, said Dr. Abraham. Most patients are eligible for a simplified treatment regimen of taking one pill a day for 12 weeks.

"Physicians just have to look for drug interactions up-front and monitor blood work to ensure response," he said. "It's very simple to learn, and primary care physicians are well capable of managing most cases without a subspecialist."

In their latest joint guidance, issued in May 2023 and published in Clinical Infectious Diseases, the AASLD and Infectious Diseases Society of America (IDSA) expanded the scope of patients eligible for simplified treatment to include those living with HIV. The simplified regimen, consisting of either eight weeks of glecaprevir (300 mg)/pibrentasvir (120 mg) or 12 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg), is recommended for all treatment-naive patients who do not have severe liver disease.

The expanded AASLD/IDSA treatment recommendations were based on findings from a study published Jan. 10, 2022, in The Lancet Gastroenterology and Hepatology. The study included 400 previously untreated patients with HCV in five countries, including the United States, 42% of whom had HIV infection. Researchers reported a 95% sustained virologic response at the end of 12 weeks with minimal monitoring—defined as no pretreatment genotyping, dispensing the entire treatment up-front, no scheduled on-site visits or lab monitoring, and two remote assessments.

As a result of such findings, the updated guidance also reduces the need for clinician intervention during treatment, including forgoing interim lab work or in-person visits for most patients. Patients are considered cured if they have an undetectable HCV RNA level at the end of therapy. No additional follow-up is necessary for patients without liver disease.

Reaching those at risk

Despite the existence of an effective, simplified treatment, getting it to patients who need it most is a major obstacle to achieving national and global targets of eliminating HCV as a public health threat by 2030, said Lauren Beste, MD, MSc, FACP, associate professor of internal medicine at the University of Washington School of Medicine in Seattle and a member of ACP Gastroenterology Monthly's editorial advisory board. Many of those at highest risk for infection do not have a medical home, she noted.

"HCV can affect anyone, but the highest prevalence is among people who use injection drugs or who are incarcerated," said Dr. Beste, who is also deputy director of the general medicine service at VA Puget Sound. "Part of our struggle is how to get care to those groups."

Insurance status has a significant impact on access to treatment, according to the CDC's Aug. 12, 2022, Morbidity and Mortality Weekly Report. Using insurance claims data for adults ages 18 to 69 years with HCV infection, the report found that only one-third of those with private insurance and one-quarter of Medicaid and Medicare recipients had started treatment within a year of their diagnosis.

The lowest treatment rates were among adults between ages 18 and 39 years, groups that also have the highest rates of acute HCV infection, often associated with injection drug use, the report stated. Medicaid recipients, in particular, were less likely to receive timely treatment despite its substantial clinical and cost benefits, including slowing disease transmission and preventing cirrhosis, liver transplants, and liver cancer.

Some state Medicaid programs also impose burdensome restrictions on treatment for eligible patients, such as liver fibrosis status, preauthorizations, and sobriety requirements, according to the MMWR report.

A recent study by the VA, published Jan. 27 by Clinical Infectious Diseases, suggested that an integrated or closed health care system can achieve better results. Among more than 133,000 veterans with HCV included in the study, 80% initiated treatment and more than 90% were effectively cured. The authors noted that the high rates were achieved with the help of dedicated government funding, a national informatics infrastructure, and proactive outreach, monitoring, and follow-up by clinicians.

"The VA invested a lot of effort into identifying, testing, and treating our population—which historically has had a higher prevalence of hepatitis C than the general population—and it's been close to eliminated," said Dr. Beste, coauthor of the study. "We know who our patients are, who's been tested, and how to reach them. That's hard to replicate in a nationwide setting, but hospital or health care networks can use it as a model."

Another part of the solution is meeting patients where they are through alternative care settings and delivery models, said Dr. Litwin. More funding is needed for programs that get care to high-risk groups using telehealth, mobile clinics, or paramedics who travel to people's homes or homeless sites. "Mobile programs can link these people to care that they wouldn't otherwise seek out," said Dr. Litwin.

Education around HCV best practices is especially important for physicians working in inpatient treatment clinics for substance use, where most patients are motivated to be in recovery, said Dr. Abraham. However, it can be challenging to complete treatment because not all patients finish their programs or maintain sobriety.

"We need a minimum of 12 weeks to follow patients and make sure they respond to therapy," Dr. Abraham said. "If they stop early and subsequently reinfect themselves, we're back to square one."

Where to learn more

Online courses are readily available for physicians to learn best practices for screening, diagnosis, and treatment. For example, the CDC-funded Infectious Diseases Education & Assessment website based at the University of Washington, offers a variety of free resources on HCV, including CME-accredited self-study courses.

Physicians can also connect with an existing Project ECHO HCV program for training and ongoing mentorship, said Dr. Thornton. In addition to the New Mexico Viral Hepatitis ECHO that Dr. Thornton leads, there are currently 23 other Hepatitis C ECHO programs in the U.S. The ECHO programs offer regular teleconferences where participants can present their own cases (de-identified) and learn from HCV experts as well as their peers.

"We train physicians on who to test and how to evaluate liver disease, since cirrhosis of the liver affects treatment decisions," she said. "We also teach them about antiviral medications and how to match patients with the best treatment regimens."

Initiatives like Project ECHO can have a major impact on improving access to care, said Dr. Beste, who led a 2017 study looking at the effect of Project ECHO on engaging veterans in treatment in rural, primary care settings.

"Using ECHO is one reason we were successful in treating 90% of our population," she said. "One of its strengths is offering a community of practice, which is especially important in rural areas where physicians can feel isolated. It's incredibly affirming for them to know that they have support and can connect with an expert when they have questions."

There's a strong case for making HCV part of routine care because it has such a major impact, said Dr. Thornton. Additionally, treatment can mitigate other issues—for example, patients with chronic HCV are much more likely to develop diabetes than patients without the disease, and treating HCV can improve diabetes control.

"Hepatitis C is one of the easiest and most satisfying things to treat in medicine," she said. "We can cure someone of an infectious disease and actually change their life."