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Vol. LXIV, No. 6
March 16, 2012
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Applying a ‘Modern Day Miracle’
Liver Transplantation Expert Ascher Shares Wisdom, Insight

On the front page...

If anyone wants more proof that obesity in America is out of control, they need only look at NASH numbers over the last two decades, according to recent Clinical Center Grand Rounds “Great Teacher” Dr. Nancy Ascher. Professor and chair of surgery at the University of California, San Francisco, she shared wisdom and insight from her 30-year career in the field of organ—specifically, liver—transplantation.

Non-alcoholic steatohepatitis, or NASH, she said, is “the newest kid on the block” of disorders indicating liver transplantation. Growing obesity trends in the U.S. over the last 20 years have contributed to increasing NASH diagnoses.

Ascher showed a graph of state obesity rates according to population body mass index (BMI) readings of 30 or greater, which defines obesity. In 1990, no state reported higher than 19 percent of its population fitting the definition. By 2009, all but one state reported at least 20 percent of its population could be determined to be obese.

Continued...

“The incredible epidemic of obesity in the U.S. is reflected in patients listed for transplantation who have [NASH],” she said. “Chronic active hepatitis C, which is the most common indication for liver transplantation in the U.S. today, is being surpassed by [NASH], unless you come up with a treatment for this disease.”

Introduced as a “master tinkerer and brilliant thinker” by Dr. Jake Liang, chief of NIDDK’s Liver Diseases Branch, Ascher began her talk with a short history lesson in the “modern day miracle” of organ transplantation.

Before the lecture, Dr. Jake Liang (l) and Dr. Theo Heller (r), both of NIDDK, chat with Clinical Center Grand Rounds “Great Teacher” Dr. Nancy Ascher, professor and chair of surgery at UCSF.

Before the lecture, Dr. Jake Liang (l) and Dr. Theo Heller (r), both of NIDDK, chat with Clinical Center Grand Rounds “Great Teacher” Dr. Nancy Ascher, professor and chair of surgery at UCSF.

Photos: Ernie Branson

She recalled a New York Times article in 2004 celebrating the “Ultimate Gift: 50 Years of Organ Transplants.” The first successful live-donor kidney transplant surgery was performed in 1954. The first-ever kidney transplant had been done in 1947 using a cadaver organ. The first liver transplant was completed in 1963. In recent years, hands and faces have been transplanted.

“When you think about it,” Ascher said, showing a timeline tracing the field’s beginnings, “we are approaching the time when we can replace any solid organ.”

Zeroing in on her specialty, Ascher noted 10-year survival rates after liver transplant: Using a live-donor liver offers the highest survival rate at 85.2 percent; transplant with cadaveric organs offers 59.4 percent. “Transplantation,” she said, “is no longer an experimental procedure.”

Ascher covered a lot of ground in a short period. She discussed the need for live donors and how distribution decisions are made.

“The need for live-donor transplant is great,” she said. “There are approximately 18,000 people waiting on the liver transplant list, but only about 6,000 receive a liver transplant. About 10 percent of patients on the U.S. list die while waiting. About 11 percent of our [UCSF] patients on the list in 2010 died without transplant.”

Ascher said the Model for End-Stage Liver Disease, or MELD, was put in place in 2002 for adult patients on the waiting list for organs. MELD is a formula that uses lab results—bilirubin, creatinine, INR—to calculate the severity of a patient’s illness.

“The higher your MELD score, the more likely you are to get a transplant,” Ascher explained.

“The purpose of creating the MELD was to prevent patients from dying on the transplant waiting list.”

Ascher also talked briefly about the UCSF liver transplant program, the largest in northern California and one of the largest nationwide. She and two associates started the program in 1988. More than 2,600 liver transplants have been performed there to date.

Ascher shared UCSF’s report cards. “We are judged by how well we do with transplant relative to how gravely ill our patients are,” she said. The program gets examined every 6 months. UCSF scored 93 percent in observed patient survival 1 year after surgery. That significantly beat the expected outcome of 88.4 percent and the national score of 88.6 percent.

Ascher discusses UCSF’s liver transplant program, the largest in northern California and one of the largest nationwide. She and two associates started the program in 1988. More than 2,600 liver transplants have been performed there to date.
Ascher discusses UCSF’s liver transplant program, the largest in northern California and one of the largest nationwide. She and two associates started the program in 1988. More than 2,600 liver transplants have been performed there to date.

“Over the last 8 report cards, we had superior survival in all grade periods,” Ascher noted. “With the use of a dedicated team of physicians— surgeons, hepatologists, anesthesiologists, infectious disease, nursing, social work, psychiatry—we are actually able to achieve great success.”

The surgeon, who also has published more than 300 research papers, talked about the transplantation operation itself and risks to live donors. She gave some insight on her program’s experiences and techniques.

Ascher said two important observations about the liver have guided the field: the liver can be divided into sections and segments can be removed; and the liver regenerates itself.

“If I take out two-thirds of your liver,” she said, “your liver will grow back. Of course this is the basis for doing liver resection and for doing live-donor liver transplant and split-liver transplant.” Donors regrow their liver volume, about 95 percent, within a month. The recipient, because of therapy drugs, takes about 4 or 5 months to regrow the liver.

Showing a CT scan of a donor’s liver 6 months after donation, Ascher pointed out where the liver had recouped its original volume, but regrown in an entirely different shape. The colon filled in empty adjacent space around the liver as it regrew.

“It’s interesting,” she said, “that we don’t know what the long-term complication will be for donors.”

Ascher explained an approach UCSF and the University of Nebraska have taken to remove a smaller portion of the donor’s liver “to decrease danger to donor and somewhat increase danger to recipient.” Both programs use a porto-caval shunt to bypass some blood flow away from the small portion of liver, in effect allowing it to grow. Other programs solve the donor-risk problem by using small portions from two donors, in effect putting three people at some risk.

In Q&As, she addressed several issues, including the possibility of using stem cells to grow liver tissue.

“I think that has incredible potential,” Ascher said. “We’ll see how it all sorts out. We also think that the field of stem cell biology will allow us to avoid the use of immunosuppressant drugs.”

Ascher’s Feb. 8 lecture is archived under Past Events at http://videocast.nih.gov/. NIHRecord Icon


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