Historically, medical science’s fight against infectious disease is an incremental affair, adding one small victory to another in the hope of giving humans the upper hand against microbial pathogens. Final conquests are all but unheard of. We’ve notched only one total victory so far: against the smallpox virus, which the World Health Organization declared eradicated in 1980.
But medical research has now crossed another threshold that may one day be seen as significant as the discovery of the smallpox vaccine. Beginning in 2014, the U.S. Food and Drug Administration began clearing a new class of drugs, direct-acting antivirals (DAAs), for the treatment of hepatitis C. The drugs work by blocking the hepatitis C virus’ ability to replicate itself in host cells.
Hepatitis C is a communicable disease passed almost entirely through blood-to-blood contact, and about 15 to 40 percent of those infected fight off the infection within six months. The remaining 60 to 85 percent enter a chronic phase of disease in which the virus takes up permanent residence in the liver, inflaming and damaging it over a period of years. About two-thirds of chronic patients develop cirrhosis, an advanced liver disease that can develop into life-threatening conditions such as liver failure, hemorrhage, or cancer. Hepatitis C claims about 19,000 American lives annually.
These life-threatening conditions often take years, even decades, to manifest, and many Americans with it remain unaware they’re infected with hepatitis C virus (HCV). According to the U.S. Centers for Disease Control and Prevention (CDC), the vast majority – three-quarters – of the 3.5 million Americans infected with HCV are baby boomers, born from 1945 to 1965.
The advent of DAAs marks a distinct transition. The old standard treatment for HCV – injections of the antiviral protein interferon, accompanied by oral intake of the drug ribavirin – is the standard no more. It was a notoriously grueling treatment that could last as long as 48 weeks, fraught with unpleasant and often debilitating side effects, and resulted in an overall cure rate of 50 to 60 percent. DAAs are pills that can be taken orally, one pill a day, for a period of 12 weeks (up to 24 weeks for some patients, such as those with decompensated cirrhosis), with fewer side effects and an astonishing cure rate of around 95 percent.
Before DAAs were introduced, nearly 10 percent of American veterans were infected with the HCV virus – a rate of infection four times higher than that of the general population. The Veterans Health Administration (VHA), the largest single HCV care provider in the United States, is uniquely suited to treat HCV infection, and it has responded to the advent of DAAs with a robust screening program: So far, about 78 percent of veterans in the baby boomer cohort who are enrolled in VA benefits have been tested for the disease. Since the drugs were first made available, the VA has treated more than 90,000 patients, and continues to treat about 2,000 veterans every month.
Maggie Chartier, Psy.D., M.P.H., psychologist at the San Francisco VA Medical Center and deputy director for VA’s HIV, Hepatitis and Related Conditions (HHRC) Program, said the introduction of DAAs “has changed everything. I feel really lucky to be part of the program at this time. It’s a totally different treatment than it used to be, not only in its effectiveness, but in that there are very few side effects.”
BARRIERS TO HCV DIAGNOSIS AND TREATMENT
You might think the discovery of a pill that cures about 95 percent of people infected with HCV would spell the end of the disease. But the problem of HCV, and of connecting veterans to these new cures, isn’t simple. From the outset, the drugs presented a daunting obstacle for a nationwide medical system: They are among the most expensive oral medications ever produced, with a single pill’s wholesale acquisition cost ranging from $650 to $1,125. The average cost to cure a single patient, then, is estimated to be around $84,000.
Last year, with help from congressional appropriators, the VA – which has received a significant discount on its DAA purchases – was able to announce that these costs would be no obstacle: The department’s policy would be to treat all veterans with HCV, regardless of cost or the progression of the disease. Chartier and others see this new era as a window of opportunity to get as many veterans into treatment as quickly as possible.
Even without resource constraints, this opportunity presents a new set of challenges, given the number of veterans – around 234,000 – with chronic HCV. The VHA can only provide care to the veterans enrolled to receive care – and only about 30 percent of U.S. veterans are enrolled in care. Despite the VHA’s impressive record of screening and treating, Chartier said, “We estimate that if all veterans in care who are at the highest risk for hepatitis C were tested, we would have approximately 15,000 undiagnosed veterans – 15,000 people we haven’t found yet who have hepatitis C. Compared to the 200,000 we started with, it’s actually a pretty reasonable number for us. And we’re doing a lot of outreach to try to get to those patients.”
The VHA has been able to remove many restrictions on who is eligible for treatment for hepatitis C – those with ongoing substance abuse issues or advanced liver fibrosis are not automatically excluded, for example – but as the number of cures for veterans in care increases, so does the proportion of those who, for a variety of reasons, remain essentially non-treatable. “Basically we treat everybody that we possibly can,” said Chartier, “but there is a group of patients who are going to be a challenge to treat.” A relatively small number of veterans have unstable or uncontrolled medical conditions in addition to hepatitis C – comorbidities – that exclude them from care, such as incurable liver cancer.
Most of the comorbidities that keep people from HCV care, however, are psychosocial. While taking a pill a day for 12 weeks may seem simple to most healthy people, not everyone is able to do it, and failure to stick with the regimen risks making the virus drug resistant. Some patients, Chartier said, have psychiatric or substance abuse issues that make it difficult for them to adhere to the treatment – homelessness, an uncontrolled psychotic disorder, uncontrolled depression, or an untreated substance abuse disorder, for example.
Because hepatitis C is a slowly progressing disease, Chartier said, there is also a significant number of veterans who simply choose not to get treated. “If you’re not drinking, if you’re not overweight, or aren’t taking other medications onboard that affect the liver, it’s very possible that you can have hepatitis C and it won’t actually be damaging your liver that much,” said Chartier. “So some people might make a decision not to get treatment until they get to a different disease stage.”
The VHA estimates that as many as 30 percent of the veterans in care with HCV who are awaiting treatment are either unable or unwilling to begin – and so in recent years it has redesigned its system of hepatitis C care, to both reach out to these “non-treatable” veterans with HCV and to optimize its quality of care.
MORE TESTING, BETTER TREATMENT
Armed with a new class of drugs that will cure nearly every veteran infected with HCV, and the resources to provide that cure to any veteran for whom it’s indicated, the VHA has redoubled its commitment to providing efficient and effective HCV care.
First, the VHA has assembled a national Hepatitis C Resource Center, consolidating existing centers at several Veterans Integrated Service Networks (VISNs) – regional groupings of VA medical centers and clinics. Dr. Timothy Morgan, a hepatologist at the VA’s Long Beach Healthcare System, directs the center. “The primary purpose of the Hepatitis C Resource Center,” he said, “is to monitor and improve the care for hepatitis C across the entire VA system.” The primary program established to do that is the Hepatitis C Innovation Teams, or HITs.
Each of the 18 VISNs now has a designated multidisciplinary team of experts examining hepatitis C testing and treatment at each VHA facility – and in some cases, at community-based outpatient clinics where hepatitis C care is delivered. Ideally, Morgan said, each HIT is led by a system redesign expert – a person schooled in what’s known as “implementation science” – who can maximize efficiency and effectiveness, and the team also includes clinical pharmacists, physicians, and nurses. Team composition varies across the VISNs, but each shares the same basic purpose: to identify barriers to testing and treatment at each facility, and to devise strategies for overcoming those barriers.
Though they’re only a few years old, Morgan said, the HITs have already started to produce results. At the national level, team leaders have arranged for social workers to offer guidance in working with patients with psychosocial issues, such as homelessness or substance abuse. Among themselves, teams have shared best practices and successful approaches to problem-solving. “A recent example of that,” Morgan said, “was an electronic system that identifies patients who have not been screened for hepatitis C, and then automatically sends a letter to those patients. The letter says the VA recommends all patients born between 1945 and 1965 should be screened, and encourages them to bring the letter to their next VA appointment. That was one facility’s idea that’s now spread to other facilities.”
In the last four years, as the HITs have been implemented across the VHA, the screening rate for hepatitis C in the baby boomer cohort has increased dramatically, from 65 to 78 percent. “My personal opinion,” Morgan said, “is that the HIT teams contributed to that.” The teams have also, he said, made the system of HCV care more standardized by exporting best practices and improving the performance at struggling facilities.
While the HITs work to improve testing and treatment, the Hepatitis C Resource Center carries out several tasks to boost their efforts. It works with Population Health Services, in VHA’s Office of Patient Care Services, to collect, disseminate, and update data on how facilities are doing – dates of testing and treatment starts, for example. It conducts educational programs for patients, producing materials that inform them about the screening process and available treatments.
For VHA providers, the Resource Center has produced a revised document of treatment considerations, providing an overview of which drug regimens are most appropriate for patients with certain genotypes of HCV. It has a designated liaison, one of the HIT team leaders, who focuses on getting care to veterans who live in rural areas, far from VHA facilities.
“The traditional way medicine has worked is that a patient goes to their primary care doctor, and the primary care doctor will say, ‘You have hepatitis C,’ and send that patient off to a specialist,” Morgan said. “We’ve finally decided that model is not the way we want to run things. We’ve decided we’re going to be proactive and try to reach out to the patients where they are, and work with the doctors in those areas to get more patients into treatment.”
The VHA recently launched an advertising campaign, targeting the 16 U.S. cities with the highest number of veterans with hepatitis C who are in VHA care and haven’t yet been treated. In addition to messaging on billboards, public buses, and kiosks, the campaign will place messages – stories told by veterans who have received hepatitis C care from the VHA – in both print and online publications.
“We hope this will bring more people who may be eligible into VA care,” said Chartier, “and for those who may be more reticent about Hep C treatment, for whatever reason, maybe helping to motivate them to come in for treatment.”
Chartier, Morgan, and their colleagues throughout VHA’s Viral Hepatitis Program see a rare opportunity – free of resource constraints, they at last have the capability to cure nearly every veteran with hepatitis C. The challenge will be to optimize the VHA’s clinical resources and its support system for care providers.
“We have very motivated providers on the ground,” Chartier said, “who’ve really been struggling with treatment for years and years – because the treatments we had weren’t very good, and they were really hard to be on if you were a patient. And then all of a sudden here is this medication that can treat almost everyone who comes in the door, and it’s really easy to take, and we have the money to do it. It’s been this perfect nexus that will allow us to do amazing things. So, we’re trying to capitalize on that momentum and treat as many people as possible.”
This story originally appeared in Veterans Affairs & Military Medicine Outlook. Click here to view to read Outlook.