Now That We Have a Cure for Hepatitis C, What Are the Next Treatment Challenges?

Within the next few years, several pipeline hepatitis C (HCV) drugs are expected to be approved in the United States, ensuring that even the most difficult-to-treat patients will soon be able to be cured, according to experts interviewed at The Liver Meeting in Boston.

"Very few patients are being warehoused because there are only a few very niche special populations left," noted Robert Brown, M.D., M.P.H., Gladys and Roland Harriman Professor of Medicine at Weill Cornell Medicine in New York, who summarized data presented at the meeting's Hepatitis Debrief.

"There are three new regimens that we are learning about at this meeting ... that will address the unmet need that remains," said Paul Pockros, M.D., director of the Liver Disease Center Scripps Clinic in La Jolla, California. Those include new regimens from Gilead, AbbVie and Merck, which will be able to cure patients who previously failed treatment, patients with patients with renal failure and genotype 3 patients with cirrhosis.

"Probably the biggest group of patients to think about in the future is the treatment failure group," said Brown. Today, very few patients fail treatment, but that could change as more and more patients are treated and as treatment duration shortens for some patients, he explained.

Merck and Gilead, two pharmaceutical companies with hepatitis C cures, have added an additional drug to their existing two-drug regimens, and these powerful three-drug combinations will likely be able to cure most patients who have previously failed treatment. Merck's new triple regimen includes its backbone drug grazoprevir, plus two new drugs, MK-3682 and Ruzasvir, while Gilead's triple includes its backbone sofosbuvir (Sovaldi), plus velpatasvir and voxilaprevir.

AbbVie, meanwhile, is moving forward with a powerful two-drug regimen of ABT493 (glecaprevir) and ABT530 (pibrentasvir), a powerful combination that will be important for end-stage renal disease patients who cannot tolerate a nucleotide analog inhibitor, or "nuc," such as sofosbuvir.

With good treatment options for almost all patients, Brown said, the next big challenge will be to improve hepatitis C screening, to screen cured patients for hepatocellular carcinoma (liver cancer) and to help active drug users who might get reinfected.

Better Screening for HCV and Liver Cancer

Current guidelines call for routine hepatitis C screenings for people born between 1945 and 1965 (the baby boomer generation) and any other patients deemed high-risk, such as injection drug users. An estimated 3.9 million Americans are infected with hepatitis C, yet anywhere from 40%-85% might not know they're infected, according to the Centers for Disease Control and Prevention. Expanding the screening guidelines might be one way to ensure more people get tested, said Pockros.

"We should absolutely have universal screening at some point," Pockros said. "That's a no brainer." Universal testing would include a one-time test for all Americans, much like HIV guidelines. Unfortunately, only a minority of the patients who test positive for hepatitis C are actually treated, highlighting some of the lingering barriers to access spurred by high drug prices.

As more patients are tested and treated, doctors will need to do a better job of screening for liver conditions even after patients are cured of hepatitis C, Brown said. Even after patients are cured, many need to be continuously screened for liver cancer. Brown explained that it is useless to cure patients of hepatitis C if they subsequently die of preventable liver cancer.

"The guidelines are clear that cancer screening needs to continue in patients who have cirrhosis," Brown said, yet that guidance "isn't followed very closely." Brown emphasized that doctors need to be careful not to "cure hepatitis C and then ignore that patients may be at risk for other liver diseases."

Retreatment in People Who Inject Drugs

The medical community also needs to do a much better job of finding comprehensive treatment strategies for patients who inject drugs, Brown said. Most doctors agree that people who inject drugs should be treated for hepatitis C, even if their risk of reinfection is higher than that of the general population. It's a concept called "treatment as harm reduction," and the idea is that treating active drug users will diminish the pool of potential infections.

According to recently published data, reinfection rates among people who inject drugs are low, but still a cause for concern. C-EDGE Co-Star was a clinical trial that enrolled patients on opioid substitution therapy. Nearly 200 patients were followed and, of those, about half reported illicit drug use. Of those, eight were reinfected, which the authors estimated to be a reinfection rate of 2.8 per 100 person years.

"As a public health issue, if only three percent are reinfected per year, we probably are doing treatment as harm reduction," Brown said. However, he cautioned, outside of a controlled setting such as a clinical trial, the reinfection rate might be higher.

"You either have to treat enough people that the pool of infection is low, or you have to build in harm reduction, otherwise you just have a revolving door," he said. Therefore, it's essential not only to treat injection drug users, but also to build robust harm reduction programs so patients can stop using injection drugs.

"I think reinfection highlights the need to build in harm reduction as a treatment strategy," which includes helping patients seek rehabilitation, Brown said. "As physicians, I don't think we're doing our jobs if we're just curing a patient's hepatitis C without harm reduction around alcohol use and [intravenous] drug use."