Issues & Insights:
Global Success Within Reach: Preventing Hepatitis C-Linked Liver Cancer

Issue 24, Winter/Spring 2015

Advent Of Powerful New Drugs And Widespread Screening Could be Turning Point Against The Disease, Experts Say

Picture of Hepatitis C

It's been called a silent killer: The hepatitis C virus, contracted through a tainted blood transfusion, dirty needles, or even the unclean razor of a roadside barber, currently infects an estimated 175 million people worldwide.

The virus typically lurks in the body for 20 years or more before any symptoms appear, and the majority of infected people don't even realize they have it.

But then come the deadly complications of infection — a scarring of the liver called cirrhosis, and in about 2 to 3 percent of cirrhotic patients, liver cancer follows.

Experts estimate that one out of every four liver cancers globally is caused by hepatitis C, and the virus is "the most common underlying cause of liver cancer in the United States," according to Dr. Ira Jacobson, Medical Director for the Center for the Study of Hepatitis C at Weill Cornell Medical College in New York City.

Because treating hepatitis C-linked liver cancer is difficult, the best solution is to detect and wipe out viral infection before it does serious harm to the organ.

Tough Medicine
For most of the past few decades, hepatitis C-infected patients had only one regimen they could turn to: A combination of interferon and a second drug called ribavirin.

These drugs helped boost the immune system's response against hepatitis C. But for most patients, the decision to endure the injected therapy was a tough one, Jacobson said.

Interferon has to be taken for up to 2 years in once-weekly injections, he explained. And because it is targeted to the immune system and not hepatitis C, interferon "has many side effects, ranging from flu-like symptoms to depression, to suppression of blood cell counts," Jacobson said. "People generally felt relatively poorly when they took interferon."

Ribavirin, which began to be used by infected patients in 1998, had its own set of problems because it often triggered significant anemia in patients.

Even so, the interferon-ribavirin combo was still only about 45 percent effective in ridding the body of the most prevalent type of hepatitis C.

This "was clearly inadequate, particularly given the difficulties patients encountered taking these medications," Jacobson said. Many young, asymptomatic patents simply refused to take the regimen or quit midway.

New Hope
Then, around 2000, things began to change. New technologies emerged — many born of research into another deadly virus, HIV — that allowed scientists to better examine and understand the mechanisms driving hepatitis C.

Picture of a patient receiving hep-c treatment

"By studying the proteins that caused these viruses to infect cells and replicate themselves, scientists were able to find targets in the replication machinery of those viruses that could be effectively blocked," explained Dr. Channa Jayasekera, Chief Fellow in the Division of Gastroenterology and Hepatology at Stanford School of Medicine.

Out of that research emerged a new armamentarium of drugs that target enzymes such as proteases and polymerases – proteins crucial to the life cycle of hepatitis C. Block their action, as these so-called "direct-acting antivirals" do, and you block the virus' ability to replicate itself.

Giving these medicines in combination is key, according to Jacobson.

"By giving more than one drug — which was a critical discovery in the HIV field almost 20 years ago — we've learned that you can so profoundly suppress viral replication that eventually the hepatitis C virus just seems to wither away and die," he said.

And while the interferon- ribavirin regimen was like "throwing a tsunami of biological effects at patients," direct-acting antivirals have few or no side effects because the drugs are so highly targeted to the virus, Jacobson explained.

The newer drugs are taken in pill form, not injections, and a course of therapy is typically over in a matter of weeks – with much greater efficacy.

"The duration of treatment has gone down to 8 weeks," said Dr. Jagpreet Chhatwal, assistant professor in the Division of Cancer Prevention and Population Sciences at the University of Texas MD Anderson Cancer Center in Houston. "Efficacy [at eliminating hepatitis C infection] is more than 90 percent in clinical trials, and no side effects."

For his part, Jacobson said he has no problem using the "C" word when it comes to these newer medicines. "We really do believe that we are curing patients, and that's really unique in medicine – to be able to cure a viral infection," he said. In many patients, the virus is undetectable for months after the therapy stops, and it never reappears, Jacobson said.

$90,000 Per Course
So why aren't all of the millions of people infected with hepatitis C – and at high risk of liver cancer – rushing to get these medications? There are two reasons, the experts explained.

The first is cost. Gilead, the maker of one direct-acting antiviral, Sovaldi® (sofosbuvir), garnered much media attention this year when it pegged the U.S. cost of the drug at $1,000 per pill, or about $90,000 per full course of treatment.

Picture of a patient injecting oneself with treatment

"This is really the key issue with regard to these drugs: the issue of access," said Jayasekera. He and his colleagues recently published a Perspective article in the New England Journal of Medicine stressing that high prices would put these life-saving medicines out of the reach of infected people in low-resource countries, where 80 percent of infections are thought to occur.

Jayasekera remains optimistic, however. He believes that as more companies begin to develop and market their own direct-acting antivirals, competition will force prices down. Already, deals are being made – for example, Gilead has agreed to slash its price for Sovaldi® in Egypt (which has the world's highest rate of hepatitis C infection) from $90,000 per course to just $900.

At the same time, Gilead is in talks to license the drugs to lower-price, generic manufacturers in countries such as India. "So far it's the only company that I know of that has agreed to do [this]," Jayasekera said, "but I think others will follow suit."

Jacobson agreed that prices for direct-acting antivirals should fall over time. "There is certainly a commitment, as I perceive it, amongst pharmaceutical companies that are involved in this field to ultimately ensure the global availability of these drugs," he said.

Renewed Emphasis on Screening
However, all of the experts agree that one more piece of the puzzle needs to be in place if we hope to eradicate hepatitis C infection and its related cancers — improved screening.

Picture of a person getting a tattoo

There's been movement on that front, too. In 2012, the U.S. Centers for Disease Control and Prevention issued new guidelines that support the screening of all "Baby Boomers" — people born between 1945 and 1965. This was done based on "the recognition that over two-thirds of people with hepatitis C in the United States were born within those years," Jacobson said.

This generation is at higher risk because they may have received a tainted blood transfusion before 1992, when better blood screening practices came into place. The guideline does "leave some people out, but it captures in one fell swoop an enormous population of hitherto unidentified people," Jacobson said.

The cost, ease of use, and effectiveness of hepatitis C blood tests has also greatly improved in recent years, meaning that millions of people in resource-poor countries could be candidates for screening, Jayasekera said.

In an article he helped co-author, published recently in the Annals of Internal Medicine, Chhatwal predicted that if widespread screening and better treatment come together, hepatitis C infection could become a "rare disease" — in the United States at least — in the not too distant future.

Jacobson said he is also "optimistic that that will happen eventually," although more must be done before we can rid the world of hepatitis C and related liver cancers.

"We still have millions of people in whom the infection needs to be eradicated, and we have to do everything we can to ensure that new infections stop occurring," he said. "But I do foresee this as a rare disease, perhaps 20 or 30 years from now."