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New Hepatitis C Guidelines: Who Should Be Treated and When?

Everyone with chronic hepatitis C could potentially benefit from treatment with new direct-acting antivirals, but when resources are limited, people with advanced liver disease, those at greatest risk for complications, and those most likely to transmit HCV should be treated most urgently, according to new guidelines released this week from AASLD, IDSA, and IAS-USA.

The recommendations -- a collaboration between the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America, and the International Antiviral Society-USA -- are available online at www.hcvguidelines.org.

Initial guidelines, released this past January, covered hepatitis C virus testing, linkage to care, and specific treatment recommendations using new direct-acting antiviral agents, or DAAs. The expert panel -- comprised of 27 liver disease and infectious diseases specialists plus a patient advocate -- recommended the recently approved DAAs sofosbuvir (Sovaldi from Gilead Sciences) and simeprevir (Olysio from Janssen), either with interferon or in all-oral interferon-free regimens, depending on a patient's HCV genotype and prior treatment history.

The new section -- "When and in Whom to Initiate HCV Therapy"-- focuses on which individuals should be treated and when.

"Because of the myriad benefits associated with successful HCV treatment, clinicians should treat HCV-infected patients with antiviral therapy with the goal of achieving an SVR [sustained virological response], preferably early in the course of their chronic HCV infection before the development of severe liver disease and other complications," the guidelines state.

But in situations where treatment cannot be provided for everyone, "Highest priority should be given to patients with advanced fibrosis [Metavir stage F3], with compensated cirrhosis [Metavir stage F4], and liver transplant recipients, and high priority given to patients at high risk for liver-related complications and severe extra-hepatic HCV complications," the panel summarized in a press release and a July 11 media briefing.

Because interferon-based therapy was difficult to tolerate, lasted 6 to 12 months, and was only effective about half the time, treatment has traditionally been reserved primarily for people with evidence of progressive liver disease. Over years or decades chronic HCV infection can lead to serious liver complications including cirrhosis, hepatocellular carcinoma, and need for a liver transplant; however, a majority of people with hepatitis C will never progress to the most advanced stages of disease.

With the advent of well-tolerated new DAA drugs that can cure most people in just 2 to 3 months -- with several all-oral combinations demonstrating SVR rates of 90% or higher in clinical trials -- a growing number of clinicians and patient advocates are calling for universal treatment. Curing hepatitis C before advanced liver disease sets in could reverse a host of earlier symptoms and associated manifestations, as well as reducing HCV transmission -- a concept of "treatment as prevention" borrowed from the HIV field.

"Everyone living with hepatitis C who wants to be treated and cured should have access to treatment without barriers," according to a recent sign-on statement developed by a coalition of medical providers and advocacy organizations including the National Viral Hepatitis Roundtable and Project Inform.

"There is no question that treating and curing HCV can markedly reduce the progression of cirrhosis and the incidence of liver cancer, decrease the need fortransplant, and reduce the all-cause mortality of chronically infected patients," said AASLD panel co-chair Donald Jensen. "It can also reduce transmission of virus to others."

In addition to patients with advanced fibrosis or cirrhosis, the panel also prioritized people with various extra-hepatitic (beyond the liver) manifestations such as cryoglobulinemia or kidney-related complications. People coinfected with HIV or hepatitis B, those with other co-existing liver diseases such as steatohepatitis (fatty liver), and those with diabetes or debilitating fatigue are also prioritized. Furthermore, treating people who inject drugs, gay men with high-risk sexual practices, and prisoners could have a significant impact in reducing HCV transmission.

"The benefits of curing HCV are clear from the standpoint of individual patients as well as that of the health and welfare of our society," added IDSA president and panel member Barbara Murray. "This new guidance will help clinicians determine the best course of therapy for each patient given their unique condition."

But the high cost of sofosbuvir and simeprevir are already straining the budgets of private insurers and public payers such as Medicaid, Medicare, and state prisons. With an estimated 3 to 4 million people in the U.S. living with hepatitis C -- including a large proportion who rely on public medical funding -- even providing treatment to everyone with progressive disease is proving to be a challenge.

While the cost issue is difficult to avoid, the guidelines panel does not directly address the cost of new treatments in their recommendations. The panel's task was to determine optimal treatment, and drug prices are "out of our purview" as clinicians, according to Jensen.

HCVguidelines.org is a "living document" that will be updated regularly to keep pace with the development of new diagnostic tools and treatment options, said IAS-USA panel co-chair Michael Saag. Several new drugs, including Bristol-Myers Squibb's daclatasvir (Daklinza) and AbbVie's "3D" interferon-free combination, are expected to be approved within a matter of months. The next 2 sections of the guidelines will cover monitoring patients after treatment and management of acute HCV infection.

Since there are not enough liver specialists in the U.S. to see all the new patients who could seek care due to recent recommendations that all Baby Boomers born between 1945 and 1965 be screened for HCV at least once, Saag suggested the guidelines could help general practitioners and other providers manage hepatitis C treatment.

"New therapies recently approved by the FDA and those that are in the pipeline and will reach market soon will completely change the landscape for patients withhepatitis C," said AASLD CEO Steven Echard. "We have filled a void in providing reputable and timely information to healthcare providers and their patientsby addressing whom to treat and when, as well as identifying patients that are in immediate need of treatment and those who can safely wait for the next generation of drugs."

8/12/14

Sources

AASLD/IDSA/IAS-USA. When and in Whom to Initiate HCV Therapy. www.HCVguidelines.org. Updated July 11, 2014.

AASLD/IDSA/IAS-USA. HCV Treatment Recommendations Now Includes Information on Prioritizing Patients Under Limited Resources. Press release. July 11, 2014.