Is it time to screen all Americans for hepatitis C infection? A discussion with Dr. Zobair M. Younossi

Background
An estimated 3.5 million Americans have been infected with hepatitis C (HCV), according to the Centers for Disease Control and Prevention (CDC). But about half of these people aren’t even aware they’ve been infected, CDC reports. Diagnosis is important because, if left untreated, HCV can cause cirrhosis, liver cancer, and liver failure, not to mention that it’s the most common cause of liver transplantation in the United States.

For over a decade, both CDC and the US Preventive Services Task Force (USPSTF) have recommended screening for HCV infection in people at high risk. "Although screening of high-risk populations for HCV has been recommended for decades, it has failed to identify the majority of infected individuals, with less than 10% of the infected individuals receiving treatment," wrote researchers in a recent paper published in the journal Liver International.

To improve the yield of the screening, CDC, USPSTF, and prominent gastrointestinal and liver professional societies have recommended that, in addition to the high-risk groups, the baby boom generation (Americans born between 1945 and 1965) should be offered a one-time screening for HCV infection. "In fact, this screening strategy, which has been in place since 2012, is deemed to be cost-effective," noted the authors of the above paper. However, "despite the initial uptake in screening of the baby boomer cohort, there has been suboptimal implementation of this strategy," they added.

A new strategy is needed to target HCV infection. These authors suggest that "screening the general population for HCV may provide a better strategy to identify and eradicate HCV from the United States."

Such an all-encompassing strategy may indeed be more effective at eradicating HCV—but wouldn't it also be extremely costly? To find out, these researchers evaluated this "screen-all" strategy, along with two less-ambitious screening strategies, and tested their cost-effectiveness using various economic probability models.

What they found was surprising: "Screening the entire US population and treating active viremia with the currently available, highly effective treatment regimens was projected as cost-saving," they concluded. In fact, they projected that the screen-all strategy would lead to a savings of billions of dollars and improve clinical outcomes as compared with screening only high-risk patients or baby boomers.

In this interview, lead author Zobair M. Younossi, MD, MPH, Chairman of Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, discusses how the screen-all approach is not only more cost-effective but also increases patients' quality of life. In addition, he explains how he and his fellow researchers evaluated all three screening and treatment strategies, and whether such a far-reaching, screen-all approach is even feasible.

MDLinx: What prompted you to investigate different strategies for screening HCV?

Dr. Younossi: First of all, we have seen an incredible revolution over the past decade or so in the field of hepatitis C. We went from interferon-based medications—which are not only quite expensive but also have low efficacy and terrible side effects—to oral regimens with pills that almost universally cure patients with 98% sustained virologic response rate and almost no side effects. So when you have that kind of curative treatment for a disease that can cause cirrhosis, liver cancer, and is the most common indication of liver transplantation in the United States, then you'd want to provide treatment to everyone who's infected. That was our first consideration.

The second reason is that, despite the fact that we've had risk-based screening for hepatitis C for decades and birth cohort screening for years, we haven't seen a great deal of sustained uptake in adopting these strategies to identify all patients with hepatitis C. So there are hundreds of thousands of patients out there who are undiagnosed and untreated—until they come in with liver cancer or cirrhosis.

And the third consideration is the cost of drug treatment. What payers tend to focus on are the specific treatment regimen's costs. But it's not the cost per pill or cost per regimen that is important from a societal perspective. It's the cost of the entire treatment for society, and also the savings that will come from preventing advanced liver disease and improvement of other outcomes, such as quality of life and work productivity.

MDLinx: What screening strategies did you consider?

Dr. Younossi: We looked at three different strategies of screening. The first was screening for patients at high risk of HCV infection, which was defined as those patients with current or past injectable drug use as well as other known risk factors. The second was screening of the birth cohort, in which all patients born between 1945 and 1965 were offered screening, as recommended by CDC and USPTF. The third was a screen-all strategy, in which all patients over age 20 were offered a one-time screening at their annual primary care visit.

MDLinx: How did you compare these three screening strategies?

Dr. Younossi: From current statistics of the US population and from data in the literature, we made several assumptions. For instance, we assumed that 86% of the entire US population visits their primary care provider annually, where they could be offered a hepatitis C screening based on one of the three strategies described above. We also assumed that if a patient was positively identified as having hepatitis C viremia, then they would be treated with one of the new oral direct-acting antiviral agents. We then input these statistics, data, and costs into a decision analysis and a Markov model (a model of statistical probability).

In the end, it was clear that the strategy of screening all patients with hepatitis C in the United States, although expensive, is the most cost-effective from a societal perspective.

MDLinx: What did you find in terms of savings in your analysis?

Dr. Younossi: We determined that the screen-all strategy would cost $272 billion for screening and treatment of those infected. But the other two screening and treatment strategies would cost more—$274.5 billion for the birth cohort strategy and $284.5 billion for the high-risk strategy.

The screen-all strategy would also lead to more quality-adjusted life years per patient—12.19 on average, compared with 11.65 for birth cohort screening and 11.25 for high-risk screening.

It is important to note that there are two additional outcomes that we didn't include in this analysis. The first was that hepatitis C not only causes liver disease, like cirrhosis and liver cancer, but also causes a number of extra-hepatic manifestations, such as mixed cryoglobinemia, chronic fatigue, depression, diabetes, etc. These can actually cause significant morbidity and mortality, and are certainly associated with additional costs of this disease.

The second type of outcome that we did not include in this analysis was work productivity. We've shown that patients who are infected with hepatitis C have lower work productivity, which has an indirect economic impact on society.

If you add those two additional outcomes into this model, the cost savings associated with the screen-all strategy would be even more prominent. So, the strategy of screening and treating all patients is really the most cost-effective approach to get rid of hepatitis C.

MDLinx: Is such a public health initiative feasible?

Dr. Younossi: It is certainly feasible, and there are other countries that have actually taken it on. There's now a national strategy to deal with hepatitis C in Portugal and in France. Additionally, the World Health Organization is taking a similar global initiative for hepatitis C. Unfortunately, we don't have a national policy here in the United States. But if we leave it to different payers to develop their own approach to how these patients should be screened and treated, then we will not really have dealt with the major issue of hepatitis C for the entire country. So, yes, it's been done in other countries and it's something that can certainly be accomplished here, but it will require a national policy approach to accomplish this. Of course, there will be a major upfront investment at the beginning, but the savings for society will be substantial in the long run.

About Dr. Younossi: Zobair M. Younossi, MD, MPH, FACP, FACG, AGAF, is the Chairman of the Department of Medicine at Inova Fairfax Medical Campus and Vice President for Research of Inova Health System, in Falls Church, VA. He is also Professor of Medicine at Virginia Commonwealth University, Inova Campus, and Affiliate Professor of Biomedical Sciences at George Mason University, in Fairfax, VA.

This study was partially supported by Gilead Sciences.