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AASLD 2013: Liver Meeting Opens with a Focus on Hepatitis C

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The American Association for the Study of Liver Diseases (AASLD) annual Liver Meeting kicked off Saturday, November 2, with an overview for the media by AASLD president Gregory Fitz. With the first next-generation direct-acting antivirals (DAAs) poised to emerge from the pipeline, hepatitis C and its treatment have generated the most interest and excitement at the conference.

This year's 64th annual meeting registered nearly 10,000 hepatologists, gastroenterologists, infectious disease specialists, and others involved in the care of people with all types of liver disease, hailing from 98 countries.

Fitz, from the University of Texas Southwestern School of Medicine, said he has been attending these conferences for around 30 years and has seen some major changes.

"The practice of hepatology has morphed dramatically. Thirty years ago there was no liver transplantation, hepatitis C virus [HCV] was not yet identified...and sadly patients with liver disease had very few options," he recalled. But particularly in the last 10 years "a revolution has taken place...Suddenly it's realistic to think we'll be able to cure most patients with hepatitis C."

But the news isn't all so encouraging. Liver disease has gone from being the 14th most common cause of death 10 years ago to number 8 today, Fitz noted. "Most people with hepatitis C don’t know they have it, and most people who could be treated aren’t being treated."

The burden of liver disease is expected to evolve over the next 2 decades as more people are successfully treated for hepatitis C. While HCV is now the leading cause of liver transplantation, fatty liver disease is "close behind and likely to overtake it within the next 5 years or so," Fitz predicted. Once thought of as an "incidental accompaniment" of obesity, it is now clear that fatty liver disease alone can cause fibrosis, scarring, and liver failure.

Fitz highlighted 2 studies looking at hepatitis C prevalence in the U.S. An analysis of 5.5 million participants the large Veterans Administration database found that about two-third of veterans in the highest-risk 1945-1965 age cohort had been tested for HCV and 9.9% of these were found to be infected. Among veterans older than 68 and those younger than 48 years, in contrast, prevalence was 2% and 1%, respectively.

Another study looked at hepatitis C among "Baby Boomers" attending an emergency department in Alabama. Among 565 patients born between 1945 and 1965, 1 out of 8 were found to have previously undiagnosed HCV infection.

Findings from these studies provide validation of the recent Centers for Disease Control and Prevention (CDC) recommendation that all people within this age group should be tested for HCV regardless of risk factors.

Many of the most eagerly awaited presentations at the Liver Meeting concern new DAAs, especially as used in all-oral, interferon-free combinations. Fitz reviewed pre-presentation data from a few of these studies, which will be reported here in more detail when complete results are presented later this week.

Reporters' question mostly concerned issues relevant to the next wave of DAAs including issues of roll-out in clinical practice, cost, and access.

One reported asked whether expanded HCV screening will result in more people getting treatment who don't need it.

Approximately 20% of people with chronic hepatitis C will develop cirrhosis within 20 years, but it is not possible to predict at the outset who these will be, according to Fitz. Furthermore, we "don't really have answers" about how many people will develop advanced liver disease over 40 or 60 years.

Given the difficult side effects, long duration, and marginal efficacy of interferon-based therapy, many patients and physicians decided to forego treatment until there were signs of disease progression, often determined by invasive liver biopsies.

But the advent of well-tolerated, short-duration, and highly effective new drugs will change the equation," Fitz predicted. Sustained response rates for genotype 1 patients have risen from 30%-50% with pegylated interferon/ribavirin to 80% or higher with new agents.

"There's no question that untreated hepatitis C is a major cause of liver failure, and if you can be treated, outcomes are better," Fitz said, but he doesn't think treatment decisions "will ever be straightforward." While benefits for individual patients may be clear, cost will also be a factor.

"Today these [new] drugs could easily be $100,000 or more for a course of treatment," Fitz said. "We'd like to think we could make decisions about what's best for the individual, but thinking about this on a population scale is daunting."

The fact that several companies are coming out with promising new regimens around the same time raises hopes that competition may help keep prices in check.

Given recent U.S. Food and Drug Administration (FDA) advisory committee recommendations for approval of the first 2 next-generation DAAs -- Janssen's simeprevir and Gilead Science's sofosbuvir -- a question on many minds is how fast will treatment ramp up.

"I don’t think it's going to happen like that," Fitz cautioned. While there are many patients who have been waiting for the new drugs, "in the real world it takes time for things to be FDA approved, it takes time for drugs to become commercially available, and it's a challenge for all of us to optimize access, be sure we're using the right regimens, and not assume we know too much."

To that end, AASLD is working on a website that will feature a regularly updated database of DAA study results. Practice guidelines may take 2 years to develop, but "in this field, at this time, that’s just too long," Fitz said. "Guidelines have rigorous quality expectations -- and we believe in that -- but as data come out we want to get it out there in a couple weeks."

The website, he added, will not include anecdotal experience using DAA combinations "off label" that have not been tested together in clinical trials. But several reporters suggested such unauthorized use will start as soon as simeprevir and sofosbuvir are approved, likely by the end of the year.

Fitz stressed that studies are needed to determine which drug combinations work best together and what are the correct doses, and that is what AASLD will support, but he acknowledged that on an individual level "physicians will definitely do what they think is best for patients."

Beyond the cost of new therapies, Fitz also noted that liver disease is now so common there aren’t enough hepatologists to treat everyone. While infectious disease specialists are likely to increasingly treat hepatitis C, Fitz expressed hope that primary care providers will also help take up the slack, along with nurse practitioners and physician assistants. "We are very enthusiastic about broadening [the pool of] treaters," he said.

The high probability of success seen in studies of new hepatitis C drugs "is remarkably encouraging for patients and for all of us," Fitz concluded. "I've never seen the science better and never seen the hope greater. In the next 4-5 years we're going to see more of the same -- it's a really encouraging time."

11/3/13

References

LI Backus, PS Belperio, TP Loomis, et al. Hepatitis C Virus Screening and Prevalence among US Veterans in Department of Veterans Affairs Care in 2012. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, November 1-5, 2013. Abstract 21.

JW Galbraith, RA Franco, JB Rodgers, et al. Screening in Emergency Department Identifies a Large Cohort of Unrecognized Chronic Hepatitis C Virus Infection among Baby Boomers. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, November 1-5, 2013. Abstract LB-6.