The hepatitis C virus has always been an unusual disease. Largely symptom-free in its early stages, many people are unaware for many years that they have contracted the virus. But if left untreated, hepatitis C can eventually cause severe liver damage that may necessitate an organ transplant. Until recently, physicians have had only limited success in combating the hepatitis C virus, administering a lengthy combination of two drugs that completely cured less than half of the patients treated.

However, in recent months the forecast for curing hepatitis C patients became much sunnier. The near simultaneous FDA approval of not one, but two new therapies for the virus - called telaprevir and boceprevir - promises to dramatically improve the cure rate for the disease and prevent serious cases of liver cirrhosis and cancer. The two drugs are members of the same protease inhibitor class that has revolutionized HIV treatment, and adding one to the previous two hepatitis C therapies (forming what’s known as “triple therapy”) promises to increase cure rates to as high as 80 percent.

But new therapies bring loads of new questions and considerations for patients. At the University of Chicago Center for Liver Disease, which takes care of hundreds of hepatitis C patients, physicians Donald Jensen and Andrew Aronsohn organized a series of patient education sessions to address how the new therapies change the landscape of the disease. While many patients have been waiting years for the approval of telaprevir and boceprevir, choosing the right time to begin therapy is no simple decision. Because the therapy still takes between 24 and 48 weeks to complete, and must be closely monitored to make sure the protocol is successfully followed by the patient, hepatitis C clinics can only start treating so many patients at a time. In an editorial for the journal Hepatology, Jensen and Aronsohn explained why the University of Chicago has thus chosen to treat the sickest patients first, asking hepatitis C patients in the earlier, less severe stages of the infection to delay their therapy with the new agents.

To further spread information about these decisions, the basics of hepatitis C, and the impact of the new therapies, Jensen and Aronsohn agreed to film a series of videos for ScienceLife. Watch as the two physicians explain how the new therapies work, what patients can expect from the new treatment protocol, and why it is important for patients and their physician to choose the right time to start therapy.

By Dianna Douglas

Darryl Williams got winded while running an annual 10K race in Oak Park in 1995. Puzzling, since he was in excellent shape. Over the next five years, he had irregular heartbeats and felt strange sensations in his chest. But none of the treatments his doctors tried made a difference.

Allen Anderson, associate professor of medicine and director of the Advanced Heart Failure Program, met Williams in 2000. The arrhythmia was becoming life-threatening. Anderson diagnosed Williams with sarcoidosis of the heart, an inflammatory disease, and began to treat him with medication.

Williams was determined to get better. He followed his doctor’s orders and took his medications, even when they had toxic side effects. “We were able to control it for 10 years,” Anderson said. “He did his part as well, by taking care of himself.”

But Williams’ sarcoidosis continued to grow. The disease, which affects about 18 people per 100,000 annually, spread to his liver. Soon his ailing heart and liver put serious strain on his kidneys. Anderson decided that his only hope was a new heart, liver and kidney. “He was in heart failure and liver failure. He was critically ill. He was going to die.”

The criteria to be considered for a three-organ transplant are stringent. “We have to be very careful about patient selection,” Anderson said. A heart, liver and kidney transplant is a massive surgery. “We have to pick patients who have a good chance of survival.”

Williams’ case was the subject of many multidisciplinary meetings, with hematologists, surgeons, nutritionists, psychiatrists, social workers, infectious disease specialists. “The fundamental question is: are you going to commit organs to this person?” said John Renz, professor of surgery and director of the Liver Transplant Program. “You have to look at all aspects of a patient. And you have to feel that you are committing that precious resource well.”

After multiple screenings, the team was convinced. At 55 years old, Darryl Williams didn’t have any other health problems that would complicate his recovery. He was always careful to follow his doctors’ instructions, and would likely keep taking his medications after a transplant surgery. And, as important as anything, he had a large family and community of friends to support him through the ordeal.

After three months of waiting in the hospital for the transplants, Williams was rolled into an operating room.

“It’s an extraordinary surgery,” said Valluvan Jeevanandam, professor and chief of cardiac and thoracic surgery. “People don’t do well after any open heart surgery without a good functioning liver,” he said. “The liver has to filter out toxins and promote coagulation. Similarly, a new liver won’t do well without a good heart.”

He compares multi-organ heart transplants to “walking a tight rope without a net under you.”

There are other pressures, too. After leaving the deceased donor, the heart is only good for about five hours. A liver can be transplanted for 18 hours, and a kidney can sometimes be good for up to 48 hours. So, the heart goes in first.

“From a technical point of view, all three surgeries have to be perfect,” Jeevanandam said. “The challenging thing is sewing in all three organs in an environment hostile to any transplant procedure.”

The heart transplant was over in about four hours, but the heart was struggling. “We had to maintain his heart until he could get his liver,” Jeevanandam said. The surgeons used inotropes to stimulate the heart and a balloon pump to keep oxygen flowing.

Then Renz and the liver transplant team took over. read more

Regular readers of the New York Times Magazine are familiar with Diagnosis, Dr. Lisa Sanders’ long-running column of medical mysteries. With false leads, twists, and surprise endings, these hospital narratives are typically as suspenseful as a Raymond Carver story, or perhaps more appropriately, an episode of House. The subject matter of these mysteries are usually what doctors call “fascinomas,” unusual and odd maladies that one rarely, if ever, encounters in the clinic. But in this past Sunday’s installment, which featured the Medical Center’s John Henning Schumann, how a particular fascinoma was diagnosed was just as interesting as the diagnosis itself.

The story, in a nutshell: a 40-year-old friend of Schumann’s was suffering nightly fevers of unknown origin, and doctors were stumped. A multitude of tests found nothing out of sorts, save a non-cancerous mass in the patient’s liver that appeared to be a hemangioma - a cluster of blood vessels. Hemangiomas don’t typically cause fevers, so the patient’s doctors were unsure whether to perform the major surgery required to remove the mass from the patient.

And then: the internet! Amid his doctors’ uncertainty, that patient (an internet expert) and his significant other decided to start a blog about the medical mystery in which he found himself the central character.

“They had a huge social network of very over-educated people, many doctors, many not, but people connected to doctors,” said Schumann, an assistant professor of medicine. “Their attitude was let’s put it out there and see what they think.”

Schumann, a concerned observer from afar, posted a link to his friend’s blog on his own blog, Glass Hospital, and the story was picked up by Kevin Pho, founder of the popular medical blog KevinMD. Pho’s post drove traffic to the patient’s blog, where doctors left comments with diagnosis suggestions and links to published obscure case reports similar to his ordeal.

The commenters’ consensus - that the hemangioma was the likely cause of the symptoms and should be removed - agreed with the eventual, independent assessment of the patient’s doctors. But Schumann said in an interview with ScienceLife that the process was still helpful to his friend, if mostly in a psychological sense.

“I don’t think it necessarily solved the case, but I think it might have expedited it slightly, and it provided a ray of hope,” Schumann said. “For a guy who is web-savvy, it gave him a level of comfort that I don’t think all the medical specialists in the world could provide.”

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Six weeks ago, the surgical team responsible for the first successful living-donor transplant were reunited at the University of Chicago Medical Center with Teri and Alyssa Smith, the mother and daughter who were donor and recipient in that historic surgery 20 years ago. But the conference was held on October 16, jumping the gun slightly, as the actual anniversary of the living-donor transplant was November 27, 1989. November 27, 2009 fell on the day after Thanksgiving, making the fuzzy date of the conference understandable, and also providing a valid excuse for why your ScienceLife editors completely missed our own plans to mark the occasion.

But it’s not too late to share with you the videos we shot at the conference with Alyssa Smith, now 21, her mother Teri, and Christopher Broelsch, lead surgeon of the team that conducted the 12-hour surgery 20 years ago. The delay also allowed time for a touching letter to arrive at the Medical Center communications office, written to Alyssa and her family by a chemistry teacher who assisted on experiments in the 1970’s that helped pave the way for living-donor transplants. That letter was in response to Katie Scarlett Brandt’s excellent cover story for Medicine on the Midway this month retelling the story of that first surgery in 1989.

First, the videos. Here’s Teri and Alyssa talking about what they remember (or don’t remember) about the surgery 20 years ago, and the strange feeling of attending a conference where you’re the star patient:

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Alyssa Smith, now 21, was the first U.S. recipient of a living-donor liver transplant in 1989.

Today’s conference celebrating the 20th anniversary of the first pediatric living-donor liver transplant in the United States was many things: a history lesson, a technical discussion of surgical techniques, a reunion of dispersed colleagues, a media event. But most impressively, it was the rare medical conference that paid direct tribute to the reason everyone was there - the patients. Capping nearly 8 hours of presentations were brief remarks by Teri and Alyssa Smith, the mother-daughter/donor-recipient pair at the heart of that first procedure back in November 1989.

In their speeches, both Teri and Alyssa listed off things that they do that most of us would likely take for granted: dancing ballet, playing bass clarinet, going off to college, comparing clothes over a video chat. But in the context of hearing about a procedure that seems implausible even today, much less in 1989, these everyday activities were like a series of priceless gifts, given to the Smith family by medical science and the talent and care of the surgeons, pediatricians, nurses and medical ethicists 20 years ago.

Many of those personnel had made it to Chicago for today’s conference, and many of the speakers spoke lovingly of Dr. Christoph Broelsch, the lead surgeon on that first living-donor liver transplant. Broelsch was the other featured speaker of the day, but he found little to talk about after all the preceding talks had outlined the history of the procedure and how it has since spread around the world and been used to extend the lives of thousands of patients. Instead, Broelsch took the time to thank the surgical teams, here and at the two medical centers he subsequently worked at in Germany, and to talk movingly about a failed case in the early days of liver transplantation, and how difficult such failures were to face.

Also moving was Giuliano Testa, director of liver transplantation at the University of Chicago Medical Center who spoke about the importance of protecting the donors in these types of procedures. The pressure of potentially holding the key to saving a loved one’s life often puts the donor in a situation where they may not be able to make an honest decision, Testa said, reinforcing the need for independent donor advocates provided by the hospital. When all agree that donating an organ is the right decision, medically and ethically, for the donor, they should be emphatically saluted, Testa said.

“It is only through the courage of this mother [Teri Smith], and all mothers, brothers, sisters, and fathers that have gone under our knife, that not only have we saved lives, but become better doctors,” Testa said.

I took several videos of Alyssa and Teri Smith, Christoph Broelsch, and medical ethicist Mark Siegler (who was intricately involved in the 1989 case), that I will post on this site in the future. If you want to read a more detailed account of this event, my live-blog commentary remains below.

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Dr. Michael Millis with Melvin and Raquel Allen (photo by John Easton)

(See Parts One and Two here)

One week after the living-donor liver transplant surgery that saw a portion of Catherine Ortiz’s liver transferred to 11-month-old Raquel Allen, Ortiz’s family visited Allen’s family at Comer Children’s Hospital. Raquel, a day removed from the pediatric intensive care unit, looked as good as new standing on her father’s lap and munching goldfish crackers as TV cameras rolled. She also got her first chance to meet Ortiz’s 1-year-old son, Phoenix, who has already been penciled in as Raquel’s prom date 16 years from now, according to Raquel’s mother Coral Grinage.

Here’s the final video in our three-part series, where surgeon Michael Millis talks about Raquel’s long-term prognosis, Ortiz talks about her recovery from liver-donor surgery and Melvin Allen talks about what’s in store for Raquel’s birthday this Saturday.

Raquel Allen is prepared for surgery August 25th

(See parts One and Three)

One week ago today, I spent the day in two operating rooms of Comer Children’s Hospital at the University of Chicago Medical Center filming a living-donor liver transplant surgery. In one room, the patient was 27-year-old Catherine Ortiz, who had agreed to donate about a quarter of her liver to a co-worker’s young daughter. That patient, 11-month-old Raquel Allen, was brought into an adjacent operating room after doctors confirmed that Ortiz’s liver would be suitable for transplant.

After four hours of surgery, a portion of Ortiz’s liver had been removed and placed on ice as Raquel’s defective liver (she suffers from the congenital disorder biliary atresia) was removed by a second surgical team next door. After a short trip between operating rooms, surgeons placed the liver fragment in Raquel’s abdomen, then very carefully sewed blood vessels and bile ducts together to fully connect the new organ with the infant’s circulatory and digestive systems. At 4:30 p.m., Raquel’s incision was closed, and her new liver began its work - a medical achievement impossible until 20 years ago, now accomplished in less than 8 hours.

Below is a video that takes you inside those operating rooms for a glimpse at this amazing procedure. Since it is surgery, there is some blood and graphic footage, so if you are bothered by that sort of thing, take heed.

Catherine Ortiz is recovering at home after her discharge from the hospital last Thursday, two days after the procedure. Raquel Allen was moved from the pediatric intensive care unit yesterday, and will remain in the hospital for at least another week, including her birthday this Saturday. We’ll check back in with Raquel and her parents for a video to be posted later this week.

The transplant was also featured in the Chicago Sun-Times today. Part 1 of our video series, containing interviews with Raquel’s parents and Catherine, can be found here.

Raquel Allen and her parents before the surgery

(See parts Two and Three)

Twenty years ago this November, the first living-donor liver transplant was performed at the University of Chicago Hospital, transferring a portion of the organ from Teresa Smith to her 9-month-old daughter, Alyssa. In October, the team of surgeons (led by Dr. Christopher Broelsch), pediatricians and ethicists who collaborated on that historic procedure will reunite for a conference, alongside Teresa and Alyssa Smith - now 20 years old and healthy.

Surgeons continue to perform living-donor liver transplants today, and though the procedure has become practically routine for some transplant surgeons, it remains an amazing feat of medicine that seems almost improbable: a piece of one person’s organ granting new life to another. This week, one such gift played out at the University of Chicago Medical Center, as 11-month-old Raquel Allen, diagnosed with biliary atresia (a congenital disease where the liver does not properly secrete bile), received a portion of a donor’s liver. Remarkably, donor Catherine Ortiz is not related to Raquel, but is a co-worker with Raquel’s mother at a Chicago pharmacy.

Raquel’s parents, Catherine and the surgeons were gracious enough to allow us to observe the procedure as it unfolded over 8 hours last week, and for the next few days we’ll be posting a video documentary of the event in three installments. Here’s the first, which contains interviews with Raquel’s parents, Melvin Allen and Coral Grinage, and Catherine Ortiz. Tomorrow, we’ll post footage from the surgeries, and later this week we’ll check in with Raquel and her family as she recovers in Comer Children’s Hospital.

You’d rather not live without any organ, but some are easier than others to replace with technology. Kidney fails? Get dialysis. Diabetes saps your pancreas? Take insulin. Heart gives out suddenly? Try a left ventricular assist device.

Credit: HepaLife

But the liver poses a special problem. Its biochemistry is so complex that no one understands all the functions it serves, or the details of how it works. We do know it’s essential for blood clotting and for removing a wide range of toxins from the bloodstream. Acute liver failure can lead to death within 48 hours. Yet even the liver’s well-defined functions are difficult to mimic completely. Then there are the thousands of proteins the liver produces, many of which have poorly understood roles in the body.

All of that makes it hard for artificial livers to do much more than help patients survive a few more hours while they wait for a donor organ. Even the term “artificial liver” is a bit misleading, because most of the devices rely on liver cells of some kind. Duplicating their function from scratch is just too difficult. (Imagine if heart assist devices had to use actual heart muscle cells.)

As this Forbes piece observes, several companies have gone out of business trying to make artificial livers. One of the rare success stories that the story cites is a University of Chicago patient, Amy Petrovic, who nine years ago survived on a synthetic liver for a few days - long enough for her condition to improve so she could survive a liver transplant operation. 

Attempts to make reliable devices keep coming - one company this week announced plans for a new Phase III trial of an artificial liver system, and a separate trial started last month. But stories like Petrovic’s also underscore the immensity of this challenge, and the limits of medical knowledge. Many hurdles in medicine are purely technological in nature. In this case, researchers don’t know exactly where the technological intervention should start, because they don’t fully grasp the underlying biology.