Hepatitis C Update

CDC urges baby boomer testing; new drugs in development
Author: Sarah Aldridge

As baby boomers age, they’ll not only face arthritis, but the possibility of another “itis” with even greater consequence—hepatitis. In May 2012, the US Centers for Disease Control and Prevention (CDC) announced new guidelines for testing people born between 1945 and 1965 for hepatitis C.

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). It is spread via contaminated blood from an infected person, through a blood transfusion or organ transplant, or by sharing needles or equipment when using IV drugs. HCV can be spread during childbirth from an infected mother to her baby. Some people have contracted it from body piercings or tattoos.

The liver is the ultimate multitasking organ. It metabolizes carbohydrates and fats, and produces cholesterol and clotting factors. It stores iron, certain vitamins and glycogen, a source of energy. It also detoxifies drugs. If untreated, HCV can slowly destroy the liver’s cells, or hepatocytes, causing scar tissue formation. The extent of the scarring, or fibrosis, indicates the degree of liver damage. Fibrosis can lead to cirrhosis, end-stage liver disease and liver failure. HCV is the leading cause of liver cancer in the U.S.

Because HCV can take decades to develop and initial symptoms are subtle, the CDC is recommending that baby boomers undergo a one-time blood test to determine if HCV is present. The CDC estimates that routine testing could identify more than 800,000 people with HCV and save approximately 120,000 lives.

“Identifying these hidden infections early will allow more baby boomers to receive care and treatment, before they develop life-threatening liver disease,” says Kevin Fenton, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention, in a press release dated May 18.

Hepatitis C is of interest to people in the bleeding disorders community because, according to the CDC, as many as 90% of patients with  hemophilia who used clotting factor decades ago were exposed to HCV prior to inactivation procedures established in the mid-1980s.

Promising Oral HCV Drugs

At the International Liver Congress™, hosted by the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 18 to 22, 2012, data from clinical trials of three drugs to combat HCV drew global attention. Daclatasvir, GS-7977 and asunaprevir are direct-acting antivirals that disrupt nonstructural (NS) proteins HCV needs to complete its life cycle. Combinations of the oral drugs were used alone or in tandem with the standard treatment, peginterferon (PegIFN) and ribavirin (RBV).

Bristol-Myers Squibb Company’s daclatasvir is an NS5A replication complex inhibitor. It blocks enzymes HCV needs to replicate. GS-7977, made by Gilead Sciences, Inc., is an NS5B RNA-dependent RNA nucleotide polymerase inhibitor. It arrests the activity of the RNA polymerase enzyme, which provides instructions for making copies of HCV RNA.

Asunaprevir, made by Bristol-Myers Squibb Company, is an NS3 serine protease inhibitor. Like the protease inhibitors telaprevir and boceprevir, which were the first to be approved by the FDA in May 2012 (See “Sea Change,” HemAware, Spring 2012, p. 24), it prevents the serine protease enzyme from cutting a long protein into smaller functional units that HCV needs to reproduce. Researchers combined it with daclatasvir and tested the pair alone in some patients and in a “quad regimen,” adding PegIFN/RBV, in other patients.

Although none of these drugs had been tested on patients with hemophilia, some of whom have advanced liver disease, future studies of these and other drugs may be more inclusive. “Some clinical trials have begun permitting enrollment of patients with inherited bleeding disorders,” says Kenneth Sherman, MD, PhD, Gould Professor of Clinical Medicine and director of the Division of Digestive Diseases at the University of Cincinnati Academic Health Center. 

Patients with hemophilia and HCV have reason to have high hopes about improved treatments in the next few years. “We’ll see a rapid evolution of approaches as the noninterferon-containing regimens become even more potent, fine-tuned and better able to achieve viral cure,” Sherman says. Still, there is a subset of patients who can’t ditch the PegIFN-RBV duo yet. Those with cirrhosis, genotype 1a, or certain unfavorable genetic factors may not respond to early generation, noninterferon regimens as well as treatments that continue to include interferon. “In almost every study that has looked at quad therapy (two new agents + PegIFN + RBV), the difficult-to-treat patients (those with genotype 1a) are having cure rates of 90% to 100%.”

Sherman likens the current explosion of HCV therapies to HIV drug development in 1996. “What we’re seeing is the emergence of very effective drug cocktails that represent different classes of drugs with different targets working to try to suppress viral replication. This is very, very exciting.”