Also surprising: Deaths from viral hepatitis are evenly distributed between rich and poor countries. And while deaths from other infectious diseases are declining, deaths related to the liver-damaging disease have risen dramatically in the past two decades. It is now one of the leading causes of death around the globe.
The new findings emphasize the need to invest more in vaccination and treatment strategies — with lessons to be gained from both sides of the economic divide, says Graham Cooke, an infectious disease expert at Imperial College London.
"I think we all felt that hepatitis had been neglected for some time, and I think part of that was a failure to recognize how important it was," says Cooke, who led the new study. "I don't think we expected it to be figuring quite so high in the relative rankings."
Hepatitis includes a variety of diseases that cause liver inflammation. Viruses cause more than half of cases, and viral hepatitis can fall into one of several forms, most commonly: A, B, C and E.
Depending on the case, the type and the person, the disease can cause symptoms like fatigue, nausea, vomiting and jaundice. When hepatitis becomes chronic, it can lead to liver failure and death. Types A and E tend to cause acute illnesses that spread through contaminated food and water; victims usually recover. Types B and C, which are transmitted through blood and other bodily fluids, cause the vast majority of hepatitis-related deaths. Those types spread through sex, childbirth, contaminated medical equipment and dirty drug needles.
Deaths from viral hepatitis are particularly tragic because there are vaccines and effective treatments available.
To enumerate the global burden of the disease, Cooke and colleagues collected all available published evidence, which turned out to be sparse, coming from just 20 studies worldwide. The researchers also tapped into data from the Global Burden of Disease Study, a large global collaboration based at the University of Washington, Seattle.
Between 1990 and 2013, results showed a 63 percent increase in deaths from viral hepatitis, researchers reported last week in The Lancet. In 1990, the disease was the 10th leading cause of death in the world. By 2013, it had risen to the seventh leading cause. Numbers of deaths from diarrhea, malaria and tuberculosis dropped during the same time period. According to global estimates, there were 1.4 million deaths from TB, 1.3 million deaths from HIV and 584,000 deaths from malaria in 2013.
There is no single reason why viral hepatitis has lurked beneath the public-health radar for so long and in such a diverse collection of countries, Cooke says. But one explanation for its surge in both wealthy and poor countries may be that the disease can progress for years without symptoms. In the absence of regular screening programs, patients might not realize they have it until it's too late.
Cost is another major barrier on both sides of the economic divide, even though pharmaceutical companies have scaled down the price for some lower-income countries, says Rena Fox, a professor of medicine and hepatitis C specialist at the University of California, San Francisco. "Ironically, low-income countries are facing cost as a barrier," Fox says. "And high-income countries are also facing cost as a barrier."
In the U.S., a 12-week course of a new generation of hepatitis C drug can cost more than $85,000, which many insurance plans won't cover.
In Egypt, where rates of hepatitis C are highest in the world — affecting close to 15 percent of the population and killing some 40,000 Egyptians each year — the same course of drugs, billed to the government and distributed free to patients, costs $900.
But cheap drugs haven't arrived everywhere. And this persistent inaccessibility comes in major contrast to the mass-production of affordable drugs that have made a huge dent in HIV transmission in the developing world.
The World Health Organization recently updated its guidelines to strongly recommend the new hepatitis C drugs, which came out in 2013 and can cure the disease in 12 weeks. That's a helpful step but it fails to address a variety of country-specific challenges, Fox says. In China, for example, 8 million people have hepatitis C, but the new drugs have not been approved for use because they haven't been tested there.
Vaccines and educational campaigns offer more opportunities to curb the rising death rate, Cooke says, adding that when countries set ambitious goals, they make headway. Countries with national strategies include Egypt, Georgia, Mongolia and Thailand. But many countries still don't have universal vaccination programs, especially in Africa and Southeast Asia. "We can do stuff about this," Cooke says. "We're just not doing it."
By flagging the extensive impact of viral hepatitis, the new study offers an important benchmark for gauging improvement.
"Without data to understand where the problem exists and how many people we're talking about, I don't think efforts can be measured," Fox says. "Now we can spur regions and countries to start measuring their successes."