HCV elimination represents ‘win-win-win’ for patients, public health, cost savings

Every year nearly 3 million patients are diagnosed with hepatitis B and C infections, ultimately leading to 1.1 million deaths worldwide, WHO reported.

In response to this immense public health burden, WHO and other international organizations have developed goals and plans for elimination. Although implemented by most countries with many on track to reach their goals, analyses have revealed a persistent reservoir of chronic hepatitis viruses and new infections remain a threat, Sheikh Mohammad Fazle Akbar, MD, PhD, and colleagues wrote in Infectious Diseases & Immunity. In the U.S., only 6% of states are on track to achieve HCV elimination by 2030, according to a 2020 report by Mark Sulkowski, MD, and colleagues. Researchers further reported 35% of states are not expected to meet their margins by 2040.

In 2016, WHO outlined HCV elimination goals of 90% reduction in incidence and 65% reduction in mortality by 2030. While challenges persist in meeting those goals, John Ward, MD, director of the Coalition for Global Hepatitis Elimination and senior scientist at the CDC Task Force for Global Health, cited many achievements.

“There have been large improvements in infection control and prevention in health care. Blood bank screening has averted contaminated equipment exposure where millions of cases have been prevented that, in the past, were occurring,” Ward told Healio Gastroenterology. “There have also been clear improvements in hepatitis C testing and treatment. It is miraculous that we have the first cure for a chronic viral infection in the history of medicine that has proven incredibly safe and effective with very low rates of resistance.”

Although many countries continue to falter in their efforts toward HCV elimination, others have shown that effective programs and health care delivery are possible for reaching this goal. Analysis of data from the Polaris Observatory, which was presented at The Liver Meeting in 2022, showed Australia, Canada, Denmark, Egypt, Finland, France, Georgia, Japan, Norway, Spain and the United Kingdom are all on track to reach 2030 targets.

“We are definitely achieving some of the global goals for hepatitis elimination currently, and countries are demonstrating that elimination is possible, but we need more,” Ward said. “The challenge is to get more countries to make similar commitments to hepatitis elimination and put in place effective, widely available programs to detect and cure patients with hepatitis C.”

Healio Gastroenterology spoke with experts across the field to identify barriers to HCV screening and treatment and determine the necessary steps to achieve elimination.

Cost-Saving Effects of Elimination Tactics

Although HCV mortality rates will continue to modestly decline if the U.S. maintains the status quo on current elimination efforts, the Hepatitis C Disease Burden Simulation (HEP-SIM) model — a dynamic microsimulation of epidemic, disease progression and elimination strategies — revealed how an accelerated, nationally organized plan has potential to save more lives and billions in health care costs by 2050.

“By 2030, approximately 10,000 deaths can be avoided. … We expect to find by 2050 this program can result in 90,000 lives saved,” Jagpreet Chhatwal, PhD, director of the Institute for Technology Assessment at Massachusetts General Hospital and associate professor at Harvard Medical School, told attendees at The Liver Meeting. “Very similar story for hepatocellular carcinoma cases: By 2030 we would expect to see 70,000 cases avoided. By 2050, more than 100,000 cases avoided. With decompensated cirrhosis: By 2030 close to 30,000 cases can be avoided. By 2050, 90,000 cases.”

While the HEP-SIM model considers various factors, such as advances in therapeutics and diagnostics and rising incidence, it also takes into account the cost of treatment associated with different insurance models. According to Chhatwal, accelerated elimination is estimated to save $59.3 billion in health care utilization with treatment costs dropping from $45.2 billion to $20.3 billion and disease management from $87 billion to $54.1 billion.

“We cannot talk about hepatitis C or elimination without talking about the cost,” he said. “The accelerated program can result in approximately $14 billion savings in the next 10 years. … This is unprecedented. We are not just eliminating a disease as a public health threat, but also saving money, which is not common. That gives us a lot of impetus to implement such a program.”

Evolution of Treatment

Prior to 2014, the most common treatment for patients with HCV included interferon, peginterferon alfa-2a and ribavirin. However, these therapies were invasive and, according to a systematic review and meta-analysis from Aoran Luo, PhD, and colleagues, offered suboptimal cure rates of 40% to 65%, as well as side effects such as flu-like symptoms and depression.

The current standard of care for patients with HCV is direct-acting antivirals, which target specific steps in the virus lifecycle to prevent replication. Luo and colleagues further reported a sustained viral response rate of more than 90% at least 12 weeks after DAA treatment.

“Though we would always love shorter duration therapy, current treatment is 8 to 12 weeks, all oral, pangenotypic and effective with an excellent safety profile in 98% of individuals,” Nancy S. Reau, MD, Richard B. Capps Chair of Hepatology and professor of digestive diseases and nutrition at Rush University Medical Center, said. “In the rare chance of failure, sofosbuvir/velpatasvir/voxilaprevir provides 98% cure rates in these treatment failures.”

Even among non-adherent patients, Ward noted similar outcomes and cure rates.

Despite the high likelihood of achieving HCV eradication in patients, a retrospective cohort study in JAMA Network Open by Mindie H. Nguyen, MD, MAS, AGAF, FAASLD, and colleagues found that less than two-thirds of insured patients with viremic HCV received treatment with DAAs from 2014 to 2021, with a sharp decline in diagnoses and treatment reported during the COVID-19 pandemic.

Additionally, patients who received care from a gastroenterologist or infectious disease specialist with an advanced care practitioner were 65% more likely to receive treatment with DAAs compared with those who received care from a primary care practitioner (adjusted OR = 1.64; 95% CI, 1.38-1.95).

“We believe that DAA treatment for HCV can improve patient clinical outcomes and survival and that it is very safe and well-tolerated,” Nguyen, transplant hepatologist and professor of gastroenterology and hepatology at Stanford Medicine, told Healio Gastroenterology. “However, I observed in my practice that there are still many barriers to the patient — from linkage to care or connection to a clinician who treats HCV to insurance authorization and approval of medications.”

Barriers to Care, Health Care Delivery

When considering barriers to HCV care, the silent nature of the virus stands out the most, Ward noted.

According to a Mayo Clinic report, the acute phase of infection “rarely causes symptoms” and could spontaneously clear in 15% to 25% of patients. Chronic infection also may be “silent” for years, until the liver is damaged enough to cause signs and symptoms of disease.

For this reason, the U.S. Preventive Services Task Force recommends universal screening for adults aged 18 to 79 years, even in the absence of symptoms or known liver disease.

“I think clinicians under-appreciate the prevalence of hepatitis C, because it is silent for so long,” Ward said. “While injection drug use is the greatest risk for new infection, there are older persons, such as baby boomers, who were infected through unscreened blood donation before the virus was discovered or infection control improved.

“This only reinforces the value of screening — there is very little risk of getting a test and many benefits now that we have a cure. It is all about general awareness, education of clinicians and accountability.”

Other barriers include accessibility in linkage to care, delayed treatment and lack of insurance or restrictions of prior authorization from health insurance companies.

According to Reau, the need for additional genotype or laboratory testing often delays care. “We know we have active hepatitis C, but now I have to get another test to determine genotype even when it will not impact therapy.”

Ward noted what he calls a “hangover effect” from when HCV medications first hit the market at such a high price, resulting in applied restrictions by insurance companies, particularly Medicare and Medicaid, some of which included the extent of a patient’s liver damage, diagnosis by a specialist vs. primary care provider and sobriety status.

“A number of those restrictions have been lifted, but many still remain in place such as requiring prior authorization,” he said. “The drugs have dropped dramatically in price and they are highly cost-saving for the U.S. health system. For the insurance companies, there is really no rationale for restrictions; that is not patient-centered care. For good health care practice, all those restrictions need to be erased.”

Accessibility is yet another barrier to care, noted Alain H. Litwin, MD, MPH, executive director of the Prisma Health Addiction Medicine Center and professor of medicine at Clemson University and University of South Carolina.

“We have to go where the patients are — we cannot expect people to go to tertiary care centers and hepatology clinics,” Litwin said. “We know where these patients are. They are already at sexually transmitted infection clinics, in prisons and all types of addiction programs. They are also in primary care clinics around the country, federally qualified health care centers, rural health clinics, mobile health clinics and our emergency rooms.

But the truth of the matter is that many of our patients do not even come to care at all.”

The Disenfranchised Majority: Injection Drug Users

According to the AASLD and the Infectious Diseases Society of America (IDSA), injection drug use is the most common risk factor for HCV infection in the U.S. and Europe, with a seroprevalence of approximately 10% to 70%, depending on geographic location and duration of exposure.

Further, WHO reported an estimated 23% to 39% of new HCV infections are diagnosed in people who inject drugs, with one in three global HCV deaths attributed to injection drug use.

“There is a lot of stigma in relation to injection drug use and not enough programs that co-locate care, even if there is access to care,” Litwin said. “We have to understand it is about trust and the systems that have been set up. We cannot expect patients to seek care in a place where they have been disrespected, disenfranchised and treated poorly in the traditional health care system.”

Caring for this subset of patients requires various health care-related and infrastructure-related interventions, including increasing accessibility to sterile injection equipment and treatment programs. HCV elimination also requires health care services that consider a patient’s social determinants of health, ability to care for themselves and support systems.

Litwin noted facilities should also practice trauma-informed care, which calls for creating an environment of safety, trust and collaboration of providing choices without judgement.

“I am tired of seeing clinicians not understanding that what will help people is not complicated: It is the concept of being kind,” he said. “People do not fail — the system fails the people. If something is not working, then there is something wrong with how we are delivering care.”

The Last Frontier: Treating HCV in Pregnancy

Among other special interest groups, physicians need to be aware how to best treat HCV during pregnancy. Tatyana Kushner, MD, associate professor in the division of liver diseases at the Icahn School of Medicine at Mount Sinai, previously told Healio Gastroenterology that this patient group is the “last frontier of treatment in hepatitis C.”

Due to the unclear nature of current guidelines, HCV treatment during pregnancy remains a “controversial topic,” Kushner noted. However, ongoing investigation of sofosbuvir/velpatasvir in the STORC trial and data from the real-world Treatment in Pregnancy for Hepatitis C (TiP-HepC) registry have the potential to inform future guidelines on the use of DAAs during pregnancy.

“Although the current recommendations by AASLD, IDSA, CDC, U.S. Preventive Task Force and American College of Obstetricians and Gynecologists recommend screening all pregnant people for HCV, recent Quest laboratory data has shown that less than one-half of pregnant people are actually being screened,” she said. “If screening does occur in pregnancy and an individual is found to have HCV, the most common course of action is to recommend referral for HCV treatment in the postpartum period.

“The challenge with this approach is that many individuals are lost to follow-up postpartum and may even lose their health insurance coverage. As a result, there is a missed opportunity to treat HCV. This is one of the reasons that treatment during pregnancy or immediately postpartum may be a more effective approach.”

In addition to these challenges in treatment, HCV poses a risk for adverse pregnancy outcomes, such as intrahepatic cholestasis of pregnancy, preterm delivery and intrauterine growth restriction. The risk for vertical mother-to-child transmission ranges from 6% to 12%, which could lead to the development of chronic liver disease if left untreated, Kushner added.

Need for Incentivized Care, Political Action

While some experts, like Ward, believe reaching elimination goals by 2030 is still possible with doubled efforts, others remain skeptical.

“I am not sure we ever on track for elimination; we just got further away from the goal during the pandemic. Screening rates have been improving, but there remains a lag in linking patients to curative therapy,” Reau said. “In an ideal world, universal screening with efficient linkage to curative therapy, preferably at the same place you were screened, would allow us to align with 2030 elimination targets.

“However, in the U.S. that is not very realistic. Instead, targeted efforts in high-risk populations — or microelimination — is an alternative strategy.”

One way of getting to this “ideal world,” where universal screening and treatment is accessible to all, is through increased funding, Litwin noted.

“We have to be financially incentivized,” he said. “We do things in health care because of the financial models, so we need to incentivize care at federally qualified health centers and rural health clinics where they are getting additional dollars to provide this care. Hepatitis C and addiction metrics should also be part of continuing medical education and CMS metrics so that hospitals will receive financial benefits and payments for good outcomes related to this. All of the sudden, you will see resources being mobilized.”

Litwin added that none of this will be possible without a push from the American people.

“Everyone needs to be active politically on this front, we need to write our Congress, our senators and let them know that we need to eliminate hepatitis C and we need to build those programs,” he said. “While those efforts are underway, they are not funded yet. If they do not hear from the American people that this is a problem, we are not going to see change.”

Bottom line: One thing our experts can agree on is that elimination is possible. We have all the tools for implementation; we must now rely on building systems to ensure no one is left behind.

“Hepatitis C testing and treatment is very simple, very safe and needs to be made available to every American so that they could benefit from these miraculous lifesaving treatments,” Ward said. “Hepatitis elimination is a win-win-win: a win for the individual, a win for protecting the health of all Americans and a win for cost-saving in our country.”

• References:
• Akbar SM, et al. Infect Dis Immun. 2022;doi:10.1097/ID9.0000000000000020.
• Blach S, et al. Abstract 30: Updated evaluation of global progress towards HBV and HCV elimination, preliminary data through 2021. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid).
• Chhatwal J. A national HCV elimination program for the United States: Modeling of the health benefits and costs. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid).
• HCV Guidelines. HCV guidance: Recommendations for testing, managing and treating hepatitis C. Available at: www.hcvguidelines.org/unique-populations/pwid. Accessed: Feb. 7, 2023.
• Luo A, et al. Medicine. 2019;doi:10.1097/MD.0000000000015626.
• Mayo Clinic. Hepatitis C. www.mayoclinic.org/diseases-conditions/hepatitis-c/symptoms-causes/syc-20354278#. Accessed: Feb. 7, 2023.
• Nguyen VH, et al. JAMA Netw Open. 2022;doi:10.1001/jamanetworkopen.2022.45424.
• Sulkowski M, et al. Adv Ther. 2021;doi:10.1007/s12325-020-01535-3.
• World Health Organization. Global HIV, hepatitis and STIs programs. www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/populations/people-who-inject-drugs. Accessed: Feb 7, 2023.

• For more information:
• Jagpreet Chhatwal, PhD, is the director of the Institute for Technology Assessment at Massachusetts General Hospital and associate professor at Harvard Medical School and can be reached at [email protected].
• Tatyana Kushner, MD, is an associate professor in the division of liver diseases at the Icahn School of Medicine at Mount Sinai and can be reached at [email protected].
• Alain H. Litwin, MD, MPH, is the executive director of the Prisma Health Addiction Medicine Center and professor of medicine at Clemson University and University of South Carolina and can be reached at [email protected].
• Mindie H. Nguyen, MD, MAS, AGAF, FAASLD, is a professor of medicine in the department of gastroenterology, hepatology and liver transplant at Stanford Medicine and can be reached at [email protected].
• Nancy S. Reau, MD, is the Richard B. Capps Chair of Hepatology and professor of digestive diseases and nutrition at Rush University Medical Center and can be reached at [email protected].
• John Ward, MD, is the director of the Coalition for Global Hepatitis Elimination and senior scientist at the CDC Task Force for Global Health and can be reached at [email protected].