This story is about a ray of light from the darkness of the American opioid epidemic. It’s about a drug that represents one of the great triumphs of 21st-century medical science. It’s about a woman with advancing cancer who was willing to receive a hepatitis C-infected liver transplant – despite having been immersed in her husband’s brutal battles with the disease for decades. And it’s about a UCHealth transplant team capable of making the pioneering procedure happen.
Let’s throw in a bomb cyclone, too – because why not?
Hepatitis C attacks
Betty and Steve Huart got married in 1989, the year the hepatitis C virus was first identified. Steve had been a Navy hospital corpsman – a medic – from 1974-1978 and went on to become an audiologist now with the Veterans Administration. He probably contracted the virus in the course of his Navy duty. Tests on his liver came back abnormal, but until he changed jobs in 1997 the problem went undiagnosed. Hepatitis C treatment in those days was “not very effective and the side effects were horrendous. The treatment was worse than the disease,” as Steve put it.
Not that the disease was good: the hepatitis C virus attacks the liver and ultimately progresses to cirrhosis, a problem that can lead to liver failure and also increases the risk of liver cancer. Steve waited until the early 2000s, when his liver started to show real damage, to undergo treatment.
Treatment involved a combination of weekly injections of pegylated interferon and daily ribavirin pills for an entire year.
“On a Friday night I would take the shot, and the weekend was a train wreck,” he said. “Imagine a really bad case of the flu that just doesn’t go away – and every weekend it gets worse.”
The flu analogy is more than an analogy: our bodies produce interferon to battle flu viruses, and those miserable flu symptoms are mostly a function of interferon and other immune-response players as opposed to the virus itself.
Another round, another liver
The treatment didn’t work – not a huge surprise, as it only did work for less than half of patients. Meanwhile, Steve and Betty moved to Rochester, Minnesota; to Fountain Hills, Arizona; to metro Denver; to Tucson, Arizona; and, in 2013, back to metro Denver, where they settled in Highlands Ranch to be close to their son, who had just welcomed a baby daughter – the Huarts’ fourth grandchild.
Steve had, since his first stop in Denver from 2007 to 2010, been consulting with Dr. James Burton, a University of Colorado School of Medicine liver specialist and transplant hepatologist at what’s now UCHealth University of Colorado Hospital at the Anschutz Medical Campus (UCH). By 2013, a third drug, telaprevir, was being added to the interferon-ribavirin combination. The addition pushed effectiveness up to about two-thirds of patients like Steve who had failed prior therapy. But Steve would have to inject the drug cocktail for another year. He talked it over with Betty and decided to do it.
Meanwhile, Betty’s own liver had become a concern, and she started seeing Burton as a patient. Her diagnosis: nonalcoholic steatohepatitis (NASH), a serious form of nonalcoholic fatty liver disease. Her liver was already damaged to the point of cirrhosis, Burton told her, and her risk of liver cancer was high.
Another year of shots and flu symptoms and generally feeling awful later, Steve got great news: this time, the suffering had paid off. His hepatitis C was gone. Steve chose not to dwell on the U.S. Food and Drug Administration’s approval of a new drug called sofosbuvir a few months earlier, in December 2013.
Miracle drugs
Sofosbuvir (trade name Sovaldi) involved taking a single pill a day for 12 weeks. It was one of what would ultimately become four classes of direct-acting antiviral drugs to treat hepatitis C. These medications interfere with the virus’s ability to replicate, unlike interferon, which stimulates the patient’s immune system to fight hepatitis C. Over the past five years, drugs such as Harvoni, Eplcusa, and Mavyret have combined multiple classes of direct-acting antivirals into one to three pills taken once daily for eight to 12 weeks to achieve cures of hepatitis C infection in nearly 98% of patients treated and without serious side effects. Thanks to these drugs, Hepatis C, a disease quietly destroying the livers of 2.4 million people in the United States alone, has gone from being incredibly difficult to treat over the course of a year to casually eradicable within a fiscal quarter. This has been as stunning a development as any in the history of modern medicine. Like many innovations, it would become not only an end unto itself, but also an enabling technology of sorts. Steve’s wife Betty would be among the early beneficiaries.
Betty’s cirrhosis indeed had become a breeding ground for liver cancer. She started feeling, as she put it “old,” though she was only in her early 60s. She found babysitting her baby granddaughter inexplicably exhausting. She faded during family gatherings. Steve noticed her eyes yellowing – though, as he put it, “she was still beautiful to me.”
Burton followed her closely. By late 2017, a liver tumor hit the two-centimeter-diameter threshold for transplant eligibility. The process, he told her, was so: “First we watch it to make sure you qualify for a liver transplant, then we’re going to kill it, then we’re going to transplant.”
Killing it involved injecting tiny beads containing chemotherapy through the blood supply of the liver, which did its job shrinking, though not erasing, the tumors. She went on the transplant list. Her blood type B, being rare, reduced her chances of a match. Twice she was called into UCH with a possible donor match – these transplant surgeries happen abruptly – only to be sent back home. She wouldn’t travel far for fear that, should the call come in, she couldn’t get to the hospital quickly for surgery. Even closer to home she avoided mountain areas where there was no cell phone coverage. A lung scare took her off the list for a time – you don’t transplant if the cancer has spread elsewhere or if another type of cancer crops up. Fortunately neither had happened, so she went back on the list. But how long she would wait, no one could say. It could be weeks; it could be months. Meanwhile, her cancer wasn’t waiting. Fortunately, Burton had an alternative.
Hepatitis C-infected liver
He was and is the principal investigator for the University of Colorado/UCHealth site of a clinical trial called PRO-ACT that involves six medical centers around the country. The trial was launched after a 2017 meeting of the American Society of Transplantation in which experts from around the country mulled over whether and how to save lives by combining a continuing national tragedy with a proven medical miracle.
We’ve talked about the medical miracle. The national tragedy was the opioid epidemic. In 2016, overdoses related to prescription opioids, heroin, and fentanyl killed about 42,000 people in this country – more than died in car accidents. Many were young. Many had hepatitis C from sharing needles. But hepatitis C takes decades to destroy a liver, so many of their livers – not to mention kidneys, hearts and other transplantable organs – were in otherwise perfect shape. Before these remarkable hepatitis C drugs became available, transplanting such organs were acts of desperation: interferon-based treatment only worked for about one-third of transplant patients. Now, though, one could transplant the infected organ knowing that a 12-week course of pills after the transplant would wipe out the hepatitis C with near certainty.
Burton presented the idea to Betty and Steve. Steve’s initial reaction, as Burton recalled, was along the lines of “Are you crazy?” He had had chronic hepatitis C for decades, had gone through two ordeals to finally subdue it – and now his wife would be infected with it intentionally? But he quickly thought it through. Had Betty faced low odds of a cure as well as the sort of wretchedness he had twice suffered, he would have insisted on waiting for a clean liver. But these new drugs were game changers. Betty was willing to try it; Steve agreed it was worth the risk.
The hepatitis C-infected liver transplant
On March 13, 2019, the day had come. A matching, hepatitis C-infected liver was being flown into Centennial Airport. Betty and Steve headed for UCH. The drive from Highlands Ranch, usually 40 minutes, took longer on this Wednesday evening. A bomb cyclone had descended on the Front Range, dropping seven inches of snow and lashing out with brutal winds. Centennial Airport shut down. The pilot, Jason Reed, considered diverting to Pueblo and having a car drive the liver up, but the roads were in awful shape. Night had fallen; Betty and Steve waited, expecting to be sent home disappointed yet again. Then Reed managed to land at DIA despite the airport having recorded 80 mph gusts. A vehicle was dispatched to fetch the liver. They hustled Betty into surgery prep. Betty kissed her husband and they pulled the curtains – no time for long goodbyes. And neither of them felt that this would be goodbye.
“There are risks involved, but you either trust the people taking care of you or you don’t, and if you don’t, you should fire them,” Steve said later. “I had confidence in them and I knew we were in as good a place as we could be.”
CU School of Medicine and UCHealth transplant surgeon Dr. Trevor Nydam performed the surgery – Colorado’s first hepatitis-C infected liver transplant. Steve would spend the next several hours in the waiting room. Burton stopped in to see him. Here was his patient whose wife was very probably being infected at this very moment with the disease he had helped Steve beat. Morning came before Betty was out of the operating room.
The surgery went well. The new liver washed the yellow from Betty’s eyes. But she was indeed infected. A week later, she was taking Epclusa, which Gilead Sciences provided for the trial. Twelve weeks after that, her hepatitis was long gone.
By May, Betty was taking walks and short hikes; by early August, she had ridden a bike for the first time in 12 years, gone for walks and short hikes, and was in a senior-fitness class. She and Steve had started taking dance lessons. First up was the two-step.
“I got my toes stepped on,” though it wasn’t Steve’s fault, Betty admitted. “I know my own beat and I like to lead.”
Steve has reminded her that her strength won’t be back fully for a few months yet – that’s normal for a surgery as serious as a liver transplant. But she already doesn’t feel “old” anymore, she says. She’s set for trips to South Carolina and Wisconsin.
Burton reminds her that she now has a new condition called “liver transplantation.” She’ll take antirejection drugs the rest of her life, and her immune system isn’t what it was before.
Burton’s study has sponsored a second hepatitis C-infected liver transplant and a kidney transplant since Betty’s surgery – both liver patients are doing well and cured of hepatitis C, and the kidney recipient will finish treatment in a few weeks, he says. UCHealth has also done transplants with hepatitis C-positive hearts with success. When the PRO-ACT study is over, Burton says, UCHealth will offer hepatitis C-infected livers and other organs as a standard of care, assuming it’s a fit for the patient. It will take some education, he says, as well as support from insurance companies. The antiviral course costs about $25,000 – a fraction of a transplant tab – and it is becoming clear that infected organs begotten through tragedy combined with these wondrous pills can save many lives. So he is optimistic.
So are Betty and Steve Huart, and they urge others to consider following Betty’s lead.
“This is an amazing thing. It offers hope to people who don’t want to die waiting for a liver,” Betty said. “This has allowed me to be excited about having a future.”