hepatitis b in adults :: Article CreatorA Cancer-Causing Virus Hiding In Millions Of Americans
Early one morning in June, 2017, Todd Doan woke his husband, Wylliam Soliwoda-Doan, to say that he was going to the hospital. Doan, a music teacher at an elementary school in East Orange, N.J., had spent the previous week in bed with unusual fatigue and a deep, hacking cough. His upper abdomen and back hurt persistently. He'd seen his primary-care doctor, who'd prescribed Prevacid, for acid reflux; when that didn't help, the doctor referred him to get X-rays. Doan had planned to book a test within a few days. Three days later, at 3 A.M., he decided to drive to the E.R. Near his home in New Jersey to get them done immediately.
Doan, a short, bespectacled forty-three-year-old Vietnamese American with a jovial disposition, was raising three young foster kids and two adopted teen-agers with his husband. He conducted a youth orchestra in Manhattan, and on weekends he waited tables at a sushi restaurant. He hardly ever called in sick. At the E.R., the medical staff suspected a gallbladder attack and admitted him. When they performed an ultrasound, however, they detected a large mass in his abdomen. Blood tests suggested an inflamed liver.
A week of additional tests ensued. His mother flew in from Florida to be at his bedside; his only sibling, David Doan, a nurse who worked as a health-care consultant in Southern California, called in for discussions with the physicians. Eventually, a biopsy showed that Doan had a large tumor in his liver. It was caused by a persistent infection with H.B.V., the hepatitis-B virus. He needed immediate, aggressive treatment to have any chance of surviving.
Chronic hepatitis B afflicts a staggering two hundred and fifty-four million people around the planet, according to the World Health Organization—a number that approaches the adult population of the United States. And yet, a meaningful public-health effort that helps those with the disease remains vexingly elusive. In 2022, H.B.V. Killed 1.1 million people, mostly by triggering deadly liver cancer or liver failure. In the U.S., about two million people are chronically infected. (By comparison, around 1.2 million have H.I.V.) The disease is not prioritized here as a grave public-health concern in large part because most chronic hepatitis-B cases affect people of Asian, Pacific Islander, or African descent. Soliwoda-Doan was one of many Americans who had never even heard of H.B.V.
There is no cure for hepatitis B, but it is eminently preventable and treatable. Vaccines, diagnostic tests, and effective medications have been in hand for decades. In many countries, including the U.S., universal vaccination to stave off the infection in infants and children began in the nineteen-nineties. What's maddening for those alert to its dangers is that H.B.V.—a problem we know how to solve—still struggles to find attention and funding amid other public-health concerns. It continues to pose a possibly fatal threat to those who missed out on the vaccine, or who were born before universal childhood immunization.
Often, those with chronic hepatitis B are oblivious to the peril they are in. Doan, an otherwise healthy man, had lived for decades with a deadly virus in his body, and he didn't know it; now his doctors were saying that he might have only weeks to live. As his family absorbed the devastating news, Soliwoda-Doan wondered, Oh, my God, how did we get here?
"H.B.V. Is a stealth virus," William Schaffner, an infectious-disease physician at Vanderbilt University, told me. "It can smolder undetected for years before it makes you sick." Researchers in genetic archeology have identified the virus in human skeletal remains dating back ten thousand years; it has co-evolved with humanity through the millennia, finding sneaky ways to elude the immune system. The virus's components have strong similarities to our own cells' bits and pieces, making our immune systems less likely to launch full-scale counterattacks. "This is why it's so hard to cure—because it looks so much like ourselves," Thomas Tu, a virologist at the Westmead Institute for Medical Research, in Sydney, Australia, told me. H.B.V., which invades the liver, even inserts its DNA into our genomes, while also producing rare circular "minichromosomes" in the nuclei of liver cells that can generate more copies of the virus. It's one of a small number of infections known to cause cancers in people. (This includes hepatitis C, which also attacks the liver but is curable.) "I think of these viruses like submarines, lurking undetected, and then suddenly shooting cancer torpedoes," Schaffner told me.
The hepatitis-B virus is spread mainly through blood or bodily fluids. The vast majority of infected individuals worldwide are undiagnosed and untreated. In Asia and Africa, one of the primary modes of transmission is childbirth; a baby who acquires H.B.V. From her mother has a ninety-per-cent chance of developing a lifelong infection, in part because infants have such limited immunity. A chronic infection can linger silently for twenty, thirty, or even forty years without provoking symptoms, and routine health screenings won't spot it—only targeted blood tests can. At some point, the immune system finally sets out to kill the virus and clear out affected cells, but this inflames and damages the liver. Even if the body initially succeeds in suppressing the virus, it can persist, and waiting minichromosomes enable it to resurge. Untreated liver inflammation can worsen into cirrhosis and induce the development of tumors. By the time a person experiences clinical signs, such as fatigue and abdominal discomfort, it's often too late for treatments to help.
The Doan brothers and their mother immigrated to the U.S. In 1981, two years after a harrowing escape by boat from Vietnam. They settled in Florida, where their mother supported the family by cleaning toilets and then training as a cosmetologist. Though David was nearly three years older, the siblings were like twins: both were gifted self-taught musicians, Doan playing the oboe and viola and David the alto sax, bassoon, and flute. As young men, both went through the difficult process of coming out as gay in the face of stigma within the Vietnamese community. For much of their lives, they were unaware that they had each acquired H.B.V., most likely at birth, from their mother.
David found out first, nine years before his brother's fateful trip to the E.R. In October, 2008, David was living in Boston when he began feeling uncharacteristically lethargic. He was diagnosed with H.I.V., and his doctors started him on triple-combination drug therapy with a once-a-day pill. A couple of weeks later, further evaluation revealed that he had H.B.V. Fortuitously, his H.I.V. Medication contained two drugs that could also treat hepatitis B. His liver already seemed so damaged, however, that his doctors placed him on a waiting list for a liver transplant.
The H.B.V. Diagnosis was shocking for David. As a nursing student, he had received a required three-dose vaccination series against hepatitis B, and had learned about the virus during his coursework. But he hadn't realized that Southeast Asian immigrants were at greater risk for hepatitis B, or that he might already be infected, rendering the vaccine ineffective. "I never registered that I need to get tested," he told me. Over the years, none of his primary-care doctors suggested a test, either.
When David shared his diagnoses with his mother and brother, his mom, to his amazement, revealed that she was also H.B.V.-positive—she was even taking medication to fight the disease. What's more, many of her eleven siblings had it; they had apparently been infected at birth through their mother. Because the virus can also be transmitted through unprotected sex and injection drug use, stigma and discrimination around the diagnosis is common. The Doan family elders didn't talk about H.B.V., and as a result the younger generations didn't know to look for it.
David was lucky. After around six months, the antiviral therapy brought both his H.I.V. And H.B.V. Under control; he wouldn't need a transplant, but he would have to take his medication for the rest of his life. David encouraged his younger brother to get checked for H.B.V., but Doan was busy with work and family. Perhaps Doan, who felt fine at the time, didn't fully understand the danger he was in. It would be almost a decade before his illness reached a critical stage. "I wish I would have been more adamant about getting him tested," David told me.
Doan was transferred from the New Jersey hospital to a liver-care unit in Manhattan. His condition deteriorated so quickly that he was unable to complete chemotherapy or radiation treatment for the tumor. Jaundice yellowed his eyes and skin; he lost weight and was often in severe pain. His belly grew distended and hard from his enlarged liver; a buildup of fluid in his lungs made breathing laborious, and he needed a chest tube to drain it. To his loved ones, he became almost unrecognizable. After three weeks, nothing more could be done. "I've accepted it," Doan told his tearful husband. "Now you need to accept it." He moved to a hospice facility in the Bronx and died at the end of July, 2017.
In many families, H.B.V. Has left a traumatic and multigenerational wake. More than thirty years ago, Samuel So, a Chinese American liver surgeon, moved from the Midwest to California Pacific Medical Center in San Francisco, California. "I found all these Asians coming to see us for liver transplants who were dying from hepatitis B," he told me. Even medical professionals were often unfamiliar with the disease; most of So's patients had never been tested by their doctors. "People just don't know about hepatitis B," he said. "That's the major problem."
Later, at Stanford University, So founded a nonprofit called the Asian Liver Center and launched a public-education campaign, which is now known as JoinJade. These efforts helped push California, where one in seven adults is Asian, to the forefront of H.B.V. Advocacy. So and his colleagues have confronted common misconceptions about the virus—for example, a fear that it can be transmitted through casual contact—and have worked to reach those who are most vulnerable to H.B.V. Many struggle with poverty and rarely go to a physician. And the slow-motion harms of chronic hepatitis B have made it difficult to rally a robust public-health offensive. In 2016, the W.H.O. Set an ambitious mission of globally eliminating hepatitis B, along with hepatitis C, by 2030. The U.S. Department of Health and Human Services has a national viral-hepatitis plan and a road map of strategies for reaching those 2030 goals. But, despite significant progress, there isn't a single country that's on track to meet its elimination targets for hepatitis B, mostly because of inadequate political commitment and funding from governments.
"Hepatitis B continually gets sidelined," Chari Cohen, the president of the nonprofit Hepatitis B Foundation, in Doylestown, Pennsylvania, told me. She pointed out that some H.B.V.-positive people, scared of dying from liver cancer, forgo marriage or having kids, and some lose their jobs because of discrimination. "Any other disease that kills as many people, and that causes as much decrease in quality of life, would never be sidelined." The war on COVID-19, in contrast, was turbocharged. Governments unlocked emergency public funding and fast-tracked the development and approval of new tests, vaccines, and drugs. For Cohen and her colleagues, the pandemic response offers inspiration for what's possible. The best fix for hepatitis B would be an outright cure, but finding one has proven technically tricky; several pharmaceutical firms have shut down their clinical H.B.V.-research programs for lack of headway. Still, Cohen said, if the U.S. Committed a huge burst of funding toward H.B.V.-drug development, "Who knows what we could do with it?"
There are other ways to accelerate the fight against hepatitis B. For years, federal guidelines focussed on identifying adults at high risk, including immigrants, which put doctors in the awkward position of asking patients where they were born or whether they were injecting illicit drugs. Last year, the Centers for Disease Control and Prevention put out a much simpler recommendation: all U.S. Adults should get checked once for hepatitis B; since 2022, the agency has also advised that all adults younger than sixty get immunized against the virus. Diagnostics companies could also streamline the screening process by securing F.D.A. Approval for rapid H.B.V. Tests, which are available in other countries—but thus far it seems that the industry hasn't considered it lucrative enough to bother. (This may change, however: bringing such tests to market may become easier and swifter under proposed F.D.A. Rule reforms and with new funding from a federal program originally created for rapid COVID tests.)
Updated Hep B Vaccine More Effective For People With HIV
A newer vaccine against hepatitis B virus was clearly superior to an older vaccine type in inducing a protective antibody response among people living with HIV who didn't respond to prior vaccination, according to the results of an international study led by a Weill Cornell Medicine investigator.
The study, reported Dec. 1 in JAMA, showed that hepatitis B vaccine with a cytosine phosphoguanine adjuvant, known as HepB-CpG, (trade name Heplisav-B) induced protective levels of antibodies in up to 99.4% of the subjects who received it. Such protection was seen in only 80.6% of subjects who received hepatitis B vaccine with an aluminum hydroxide adjuvant, known as HepB-alum, (trade name Engerix-B).
"These results suggest a potential path forward for the large number of people living with HIV who can't get protection from older hepatitis B vaccines," said study corresponding author Dr. Kristen Marks, an associate professor of medicine at Weill Cornell Medicine and an infectious disease specialist at NewYork-Presbyterian/Weill Cornell Medical Center.
Hepatitis B virus is spread mostly by the transfer of body fluids during childbirth, sex, needle-sharing during drug use. It can establish a chronic, often symptomless, liver infection that can progress to liver cirrhosis and/or liver cancer. The World Health Organization estimated in 2022 that more than 250 million people globally were living with chronic hepatitis B infection, and that more than a million would die from it that year.
In the United States, the large population of people with hepatitis B includes an estimated 5 to 10 percent of people living with HIV. People with HIV often have impaired immunity that limits their ability to fight the hepatitis B virus or to mount a protective immune response following vaccination.
The NIH-sponsored BEe-HIVe (B-Enhancement of HBV Vaccination in Persons Living With HIV) trial is a phase 3 study with 561 participants at 40 sites across North and South America, Africa and Asia. The participants are people with HIV who reported prior vaccination against hepatitis B but lacked protective levels of antibodies. The Weill Cornell Medicine HIV Clinical Trials Unit, with sites in Chelsea and the Upper East Side, enrolled participants in New York City and contributed to the overall success of the study.
Each participant received either HepB-CpG or HepB-alum. Both types of vaccine use the same quantity of the same lab-made hepatitis B virus protein to induce anti-hepatitis-B responses; they differ primarily in their "adjuvants," which are compounds added to provide general stimulation to the immune system's ability to mount an antibody response.
The United States Food and Drug Administration (FDA) approved HepB-CpG for use in adults in 2017. The results suggest that clinicians will now prefer it over alum-adjuvant vaccines for boosting immunity against hepatitis B in adults with HIV who have little or no existing antibody protection.
Prior research has found that Heplisav-B induces high rates of protective antibody responses in patients with diabetes or end-stage kidney disease who tend to respond poorly to traditional hepatitis B vaccines. In an earlier part of the current study, Dr. Marks and colleagues also found that Heplisav-B induced protective antibody responses in 100% of people with HIV who had otherwise never been vaccinated against hepatitis B.
The new analysis included three arms: the HepB-CpG vaccine in three doses, the HepB-alum vaccine in three doses, and the HepB-CpG vaccine in its standard regimen of two doses. Both of the Hep-CpG arms were superior to HepB-alum, with 99.4% (three-doses) and 93.1% (two doses) of people in those groups showing protective levels of vaccine-induced antibodies, compared with 80.6% of those in the HepB-alum group. The trial did not uncover new safety issues.
Dr. Marks and her colleagues currently are conducting a follow-up analysis of the durability of the antibody responses.
This research was supported in part by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, through grants UM1 AI068634, UM1 AI068636, and UM1AI106701.
International Study Shows Updated Hepatitis B Vaccine More Effective For People With HIV
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