It was three days before Christmas, and Elizabeth Widders was perched in her upstairs bathroom, fastening red and green bows in the hair of her 4-year-old daughter, Liviah. But as Liviah stood in the morning light, her mother noticed that the whites of her eyes had turned yellow.

She hustled Liviah downstairs to ask her husband, Jack, for a second opinion. He saw the yellow tint, too.

Liviah and her two siblings all had jaundice as babies, and their parents, from Mason, Ohio, were familiar with the telltale signs. “I knew: This is liver stuff,” Mrs. Widders recalled.

They took Liviah to the emergency room, where she was diagnosed with acute hepatitis, an inflammation of the liver. Less than two weeks later, doctors removed her failing liver and replaced it with a new one.

Over the past eight months, hundreds of other families have been caught in similar whirlwinds, as their otherwise healthy children developed hepatitis, seemingly out of the blue. Six hundred and fifty probable cases have been reported in 33 countries, according the World Health Organization. At least 38 children have required liver transplants, and nine have died.

The cases have stumped experts, who are investigating a variety of potential causes. One leading hypothesis is that an adenovirus, a family of common viruses that typically cause flu- or cold-like symptoms, may be responsible, but many questions remain.

The revelation that Liviah’s case might be part of a larger phenomenon has galvanized her parents, who have started sharing their story in hopes of educating others about the key warning signs.

The cases are exceedingly rare, experts emphasize, and even then, most do not require transplants. “The odds of something like this happening are extremely small,” said Jack Widders, Liviah’s father.

But without a solid explanation, it feels like lightning that could strike any family.

‘Where would she have gotten hepatitis?’

The first signs of trouble came on Dec. 11, when Liviah began throwing up. At first, her parents chalked it up to overindulgence; Liviah had spent the previous night with her grandmother, who was known to spoil the children with treats. “We called it a ‘grandma hangover,’” Mrs. Widders recalled.

Liviah, a lively, athletic child, bounced back quickly, but the next day, her 6-year-old brother, Jaxson, also fell ill. He spiked a high fever and was sick for days. Liviah — who returned to school, visited a trampoline park and decorated cookies with the neighbors — seemed to have dodged the worst of it.

Until, a week and a half later, when her mother noticed her eyes. Her urine was orange, too, Liviah divulged to her.

The hepatitis diagnosis came as a shock. The condition has a wide variety of potential causes, including exposure to toxins, heavy drinking and the hepatitis B and C viruses, which are often associated with intravenous drug use. Mrs. Widders stared at her husband in disbelief: “Where would she have gotten hepatitis?”

(Hepatitis can also be caused by other viruses, although Mrs. Widders did not know that at the time.)

That evening, Liviah was admitted to the Cincinnati Children’s Hospital Medical Center. “She came in in acute liver failure,” said Dr. Anna Peters, a pediatric transplant hepatologist who was part of Liviah’s medical team. “She was quite ill.”

Over the following days, Liviah’s condition deteriorated.

One of the liver’s primary roles is to process toxic substances, including ammonia that is naturally produced in the body; when the organ is not working properly, these toxins can travel to the brain, causing cognitive and behavioral changes. As Liviah’s ammonia levels rose, she became irritable and enraged, screaming at her mother without provocation.

The damage to her liver, which produces proteins that help the blood to clot, also slowed her natural clotting response, leaving her at high risk for bleeding problems.

Doctors gave Liviah steroids to reduce inflammation and a compound called lactulose to help flush out the ammonia. She had blood transfusions, CT scans, ultrasounds and a liver biopsy. Mr. and Mrs. Widders slept at the hospital, while relatives looked after Jaxson and their 1-year-old daughter.

Liviah spent part of Christmas Day sedated, but woke up long enough to open some gifts, includingthe game Hungry Hungry Hippos. “She doesn’t remember a lot of Christmas, but she does know that Santa came,” Mr. Widders said.

Top of the list

Despite the treatments, Liviah’s clotting problems persisted and her ammonia levels remained high. She woke up agitated and confused. She asked the same questions — Could she go for a walk? Where was her brother? — again and again. She could barely get through a game of Candyland with her grandmother, who was heartbroken. “Seeing her the way that we were seeing her, just rapidly deteriorate before our eyes, it’s like, ‘How much more time do we have?” her mother recalled.

On Dec. 28, doctors broke the news: Liviah had been placed on the transplant list. Status 1A — the top priority.

Doctors decided to start Liviah on liver dialysis to remove some of the toxins from her blood while they waited for a match. The call came just days later, while Liviah’s aunt was visiting. Mrs. Widders put the transplant coordinator on speakerphone: They had a liver for Liviah.

It was a complicated moment for Liviah’s parents, their joy tempered with grief for the family of the deceased donor.

“We were staring death in the face,” Mrs. Widders said.

“That’s right,” her husband said. “And so we knew that our joy came at the expense of — ”

“Of someone else’s selfless ‘Yes,’” she continued. “Someone else’s tragedy was our miracle.”

On Jan. 1, Liviah received her new liver. The next day, doctors had her out of bed, working to regain her strength.

On Jan. 12, Liviah was discharged from the hospital. The Widders family celebrated Christmas again when they returned home, and the neighbors kept their decorations up for Liviah. “There was a night that everyone put them on,” Mrs. Widders said, “and we were able to drive around and see the lights.”

Searching for a cause

From the beginning, doctors had warned Liviah’s parents that they might never know why her liver had failed; in many cases of pediatric hepatitis, clinicians never find a cause, Dr. Peters said.

In Liviah’s case, doctors ruled out a variety of common triggers, but blood tests turned up one possible culprit: an adenovirus.

Although there was no sign of the virus in the liver, an adenovirus infection could have “triggered an abnormal immune response that then attacked the liver,” Dr. Peters said.

It was not a totally satisfying explanation, she conceded. Adenoviruses do not typically lead to liver damage in healthy children, and Liviah’s adenovirus levels were low.

The mystery did not faze Liviah’s father. “I left the hospital going, ‘You know what? She’s alive,’” he said. “I don’t really need to know what caused it.”

For Mrs. Widders, accepting the unknowns was harder, especially when Liviah had a liver rejection episode that briefly landed her back in the hospital. The setback prompted her mother to wonder whether Liviah might have some kind of genetic or autoimmune disorder, but testing turned up no evidence of that. By the spring, with Liviah home for good, her parents had made peace with the possibility that they might never get answers.

And then, in April, a friend sent Mr. Widders a text about a mysterious cluster of childhood hepatitis cases in Britain. Shortly thereafter, he saw an article saying that the Centers for Disease Control and Prevention was investigating a similar cluster in Alabama; all nine of the Alabama children had tested positive for an adenovirus.

To Mr. and Mrs. Widders, the cases sounded eerily familiar — and brought their most difficult days rushing back. “It was a little traumatic,” Mrs. Widders said. “And then there was that sorrow of, ‘Oh my gosh, this is happening to more than just Liviah.’”

So far, more than 200 potential hepatitis cases have been reported in children in the United States, according to the C.D.C. Many of the affected children have tested positive for an adenovirus — in many cases, adenovirus type 41, which typically causes gastrointestinal symptoms.

But the virus has not been found in all of the affected children, and scientists are not sure why a common childhood virus might suddenly be prompting liver damage. They are investigating whether the virus has changed and whether other factors may be contributing to the phenomenon.

It is possible that a prior coronavirus infection — or, conversely, the lack of exposure to adenoviruses during the pandemic shutdowns — may have left children more vulnerable, although both hypotheses remain speculative. It is also possible that adenovirus infections always caused hepatitis in a small subset of healthy children and that scientists were only now recognizing the connection.

“Is it an increased awareness?” said Dr. William Balistreri, the director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s. “Is it a new virus? Is it a new virus in synergy with an old virus?” He added, “I don’t think we can dismiss any of those theories.”

The absence of an obvious cause has bewildered parents, too. In April, Ashley Tenold received an unexpected call from a school nurse, who informed her that her daughter appeared to have jaundice. “She just turned yellow,” said Ms. Tenold, who lives in rural Wisconsin. “There was no coughing, there was no stomachaches. It was just another typical week out in the country.”

Her daughter’s liver was slightly inflamed, but her case, like most, turned out to be milder than Liviah’s. She was discharged after a few days in the hospital.

But the experience was still confusing and frightening, Ms. Tenold said: “It would be nice for them to get to the bottom of it so that not a whole lot more children have to deal with this.”

A new purpose

In the months since Liviah’s transplant, her parents have encouraged friends and family members to register as organ donors, and they held a blood drive in Liviah’s name. Liviah has also been helping her mother make earrings to sell to raise money for the hospital’s liver Helping Hands Fund, which provides assistance to the families of pediatric liver patients.

“We’re stepping into this purpose that we have,” Mrs. Widders said.

Liviah’s parents have also found themselves striking a delicate balance with parents worried that their own children might be next. They want others to be alert for the signs of liver problems — yellow skin and eyes, dark urine — but also to know that what happened to Liviah is rare.

“You can’t react to every vomit, you can’t react to every cold,” Mr. Widders said. “But the liver signs are unmistakable.”

Liviah, who is currently in physical therapy, is recovering well, her parents said. The whole family, aside from the 1-year-old Juliana, is also in psychotherapy to help process what they have been through. Liviah knows that her old liver was sick and that she has been given a new one, which she has named Teddi.

Mr. and Mrs. Widders also hope to make a scrapbook for Liviah that will chronicle exactly what happened to her — or at least, as much as they, and experts, have been able to make sense of.

“She’s not going to remember a lot of it, which is so great,” said her father, who has continued to record Liviah’s liver enzyme levels in a spreadsheet. “It’s way harder on the parents,” he added. “The kids are so dang resilient.”

The family is still adjusting to a new normal, which includes immunosuppressive drugs for Liviah to prevent her body from rejecting the new liver and a renewed focus on hygiene to protect her from other pathogens, to which she is now more vulnerable.

But Liviah returned to preschool and soccer and dance. On her school’s recent beach day, she wore a bikini so she could show off her eight-inch scar. She calls it her “princess mark.”