We think of HIV, TB and malaria as some of the deadliest infectious diseases on earth. And the death tolls bear that out.
But there's a family of viruses that is in the same league: hepatitis viruses.
There are five of them. Their alphabet soup of names tells us the order in which they were discovered: hepatitis A, B, C, D and E. According to a new report from the Global Burden of Disease, the viruses kill 1.34 million people a year.
By contrast, HIV/AIDS claims 1 million lives a year. Estimates vary for malaria (from 429,000 deaths by WHO's calculations to 719,000 deaths according to the new report). TB statistics range from 1.2 million in the study to 1.8 million from WHO).
The report from the Global Burden of Disease Study is conducted by the Institute for Health Metrics and Evaluation at the University of Washington and funded by the Bill and Melinda Gates Foundation (which is a funder of this blog). The 2017 update was published in the Lancet earlier this month.
The hepatitis viruses are transmitted in different ways and belong to different virus families. What they do have in common is that they can all cause liver damage, and in some cases, liver cancer. Indeed, the definition of hepatitis is "a disease characterized by inflammation of the liver." That liver damage is the main cause of death for people who are infected.
There's one more thing the viruses have in common: They're an overlooked cluster of killers. And that means the research dollars don't flow as easily as they do to HIV.
The neglect may be that the viruses "don't immediately kill you in most cases," says Brent Korba, a research professor at Georgetown University Medical Center, who works on developing new drugs to treat hepatitis B. "It takes 30-plus years," he says. People with long-term hepatitis infections often develop cancer in their 30s to 50s, when most people are at the peak of their earnings potential. "The economic impact of viral hepatitis is enormous," says Korba,
The lack of fanfare may also stem from a lack of data about hepatitis as a cause of death, says Dr. David Witt, chief of infectious disease at Kaiser Permanente San Rafael. When a person dies of cirrhosis or liver cancer, especially in poorer regions where autopsies are uncommon and laboratory testing is meager, the underlying viral infection isn't always recognized. "It's not evident," says Witt. "People don't think you have hepatitis."
And it's not a problem that's going away: "The number of deaths due to viral hepatitis is increasing over time, while mortality caused by tuberculosis and HIV is declining," WHO writes in its "Global Hepatitis Report 2017."
The main culprits
Two of the five hepatitis viruses are the main killers: hepatitis B is responsible for 815,000 yearly deaths and hepatitis C, 489,000, according to the Global Burden of Disease data.
An estimated 257 million people are living with hepatitis B and 71 million have hepatitis C, per the World Health Organization. Most of them — 89 percent with hepatitis B and 80 percent with hepatitis C — don't realize they're even infected because symptoms may not appear for decades.
In its report, WHO promised to work on making viral hepatitis a public health priority and has set an ambitious goal to eliminate viral hepatitis as a public health problem by 2030. The goal is to reduce the number of annual new cases by 90 percent and reduce deaths by 65 percent.
That will require a number of strategies to address the different types of the virus. Hepatitis B and C are spread by contact with blood from an infected person. Because doctors in poor areas may re-use needles without sterilizing them, unsafe injections are still a source of infection. Getting a transfusion of blood that hasn't been screened properly can also cause an infection. Drug users can contract hepatitis B or C by sharing needles and other drug paraphernalia.
Hepatitis B can also be spread sexually and from mother to child during childbirth. The younger you are when infected, the more likely you are to develop chronic infection that can lead to cirrhosis or liver cancer.
Most people who contract hepatitis B or C are able to clear the virus from their bodies within a few months without treatment. Their immune system is able to fight off the virus. But some people can't, so the virus lingers, and the infection becomes long-term, or chronic. Most of them will likely not show any symptoms although they can still spread the virus. But some will eventually develop complications from the infection like cirrhosis or liver cancer. By the time those health problems become evident, it's usually too late to repair the damage to the liver.
The nature of Hepatitis A, D and E
The other hepatitis viruses also contribute to the toll on public health. Hepatitis D is rare in most countries, only infecting people who have Hepatitis B. That virus can bring on complications like cirrhosis or liver cancer sooner than in a person with Hepatitis B alone, although scientists don't understand exactly why.
Hepatitis A and E, unlike the other hepatitis viruses, are usually transmitted via contaminated water or food. It's difficult to count annual cases because many people show no symptoms. And the death toll is relatively low compared to hepatitis B and C — about 30,000 a year, according to the Global Burden of Disease Report. Although in some places these viruses are omnipresent: In countries with poor sanitation, as many as 90 percent of kids under 10 have been infected with hepatitis A.
Hepatitis E often occurs in refugee encampments. An estimated 20 million people are infected every year, although only 3 million will show any symptoms. Pregnant women are especially vulnerable to dying from hepatitis E, probably because of hormonal and immune system changes that happen during pregnancy. The virus can also cause stillbirths.
But there's some good news in the form of vaccines.
A vaccine exists for hepatitis A and is widely used, including in the United States. A vaccine for hepatitis E was recently developed and licensed in China but hasn't yet been licensed in other countries.
A vaccine for hepatitis B was introduced in the early 1980s and "is a superb vaccine," says Korba. Subsequent versions have been even cheaper and even more effective. Middle and high income countries started making hepatitis B vaccinations part of routine childhood vaccinations in the 1990s, but many poorer countries have only recently been able to add the vaccine to their routine schedule, often thanks to donor funding.
"A few billion people have had the vaccine," Korba says. That effort is paying off. The rate of hepatitis B infections among children younger than five years old has dropped from 5 percent in the pre-vaccine era to just over 1 percent in 2015.
More can be done to prevent chronic infections that start early in life. Not all infants born to infected mothers are getting their first dose of the hepatitis B vaccine within the first 24 hours of birth, when it is most likely to prevent infection.
Developing a vaccine for hepatitis C has proven more difficult, but since 2014, new drugs to treat infections were licensed and have been effective. Unlike anti-retroviral treatment for HIV or current treatment options for hepatitis B that simply suppress the virus, the new treatments can completely clear the virus in about 95 percent of infected people within a year.
But the drugs are expensive, even though one manufacturer, Gilead, has made medications available at low cost for developing countries. One strategy is to get a special government license to manufacture and distribute the drugs. The Malaysian health ministry announced on Wednesday that they've approved this kind of license for the Egyptian pharmaceutical company Pharco. The Malaysian health ministry is currently conducting clinical trials for Pharco's formulation of the drugs and trials are also happening or planned in South Africa, Thailand and Ukraine.
Cheaper alternatives for hepatitis C treatment will mean more widespread use, and that possibility has hepatitis experts cautiously hopeful. "Hepatitis C could be gone in a generation," Witt says, although questions remain about how to strategically deploy this new treatment.
Rina Shaikh-Lesko is a science journalist who writes about medicine, global health and the life sciences. She can be reached @rinawrites