OneThousandOne represents the amount of time, verbally, that it takes to count to one second. In this one second of time, a great thing happened at Nebraska Medicine. In fact, several great things probably happened. A patient was cured, a researcher found the missing link, a nurse treated an injury, a doctor comforted a family or maybe a child just smiled.
Spring | Summer 2009

Creating New Pathways in Treatment

Leaders in Liver Disease

Since the inception of the liver transplant program in 1985, the surgical team that is one facet of the world-renowned liver disease program at The Nebraska Medical Center has performed 2,534 liver transplants.

Margaret Piper was number 62.

“The entire liver disease program has championed a great number of advancements, from our liver transplant program to our liver cancer treatment program and the development of potent anti-viral agents to treat hepatitis B and hepatitis C.”
Michael Sorrell, MD

A farm wife and the mother of seven children who lives near the town of Brock in southeast Nebraska, Margaret Piper contracted bronchitis in the fall of 1977. Because she was also extremely fatigued, “My doctor did something they wouldn’t do nowadays,” she recalls. “He put me in the hospital in Auburn for two weeks of what we used to call ‘R and R,’” – rest and relaxation.

While in the hospital, tests indicated a problem with her liver. “I remember thinking that’s probably why I was so run down,” says Piper.

After undergoing gallbladder surgery that failed to remedy the situation, a doctor in Lincoln recommended Piper go to Omaha to meet with a liver disease expert at the University of Nebraska Medical Center (UNMC), Michael Sorrell, MD, gastroenterologist.

Dr. Sorrell conducted several tests and found Piper had primary biliary cirrhosis, a disease in which the bile ducts in the liver are slowly destroyed. Though the cause is unclear, destruction of the bile ducts can cause harmful substances to build up in the liver and lead to cirrhosis, an irreversible scarring of liver tissue.

“Dr. Mike told me I had to take medicine that would slow the disease down,” Piper says, “but he said there was no cure.”

Michael Sorrell, MD

It took Piper some time to accept that she had a slowly-progressing disease that would likely prove fatal. “I didn’t understand it,” she says. “I never smoked. I never drank, except for milk and water. No pop, tea or coffee, either.”

Piper began treatment with Dr. Sorrell in 1978. That treatment continued until the early 1980s when Dr. Sorrell shared with her a plan for a revolutionary program being assembled at the medical center – a liver transplant program. “Dr. Mike told me, ‘If we get the unit open, you’re going on the list,’” says Piper.

On July 1, 1986, Piper was placed on the list of patients awaiting a donor liver. Five months later to the day, she was wheeled into surgery.

The liver disease program at The Nebraska Medical Center brings together expert surgeons, researchers, nurses and other medical personnel and administrative staff to afford patients innovative treatment options for all liver diseases, including cancer and hepatitis.

In addition to surgery and other treatments, research currently underway can provide an opportunity for patients to take part in clinical trials, where participants take a more active role in their own healthcare and gain access to new drugs before they become widely available.

The liver program employs diagnostic and imaging equipment, including a state-of-the-art endoscopy center that enables doctors to obtain an accurate diagnosis more rapidly and with less pain and discomfort to the patient.

“The entire liver disease program has championed a great number of advancements, from our liver transplant program to our liver cancer treatment program and the development of potent anti-viral agents to treat hepatitis B and hepatitis C,” says Dr. Sorrell, who until 2005 served as the medical director of the transplant program and as chief of the section of Gastroenterology/Hepatology at UNMC.

“Liver transplantation may be the most dramatic aspect of our program, but in the world, the treatment of hepatitis is the most important. Hands down, you can’t separate one aspect from another in valuing what our collective work means to the state of Nebraska, the nation and the world.”

Mark Mailliard, MD, gastroenterologist, is associate professor of internal medicine and chief of the section of Gastroenterology/Hepatology at UNMC.

“Hepatitis C is treatable and curable,” he says.

Dr. Mailliard, who has dedicated much of his career to hepatitis research, is hopeful the hepatitis C studies and trials he currently has underway will lead to the eradication of the disease in his lifetime.

The word hepatitis means inflammation of the liver. Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections can all cause hepatitis.

There are five forms of viral hepatitis:

Hepatitis A virus (HAV) is an acute liver disease lasting from a few weeks to several months. It does not lead to chronic infection.

Hepatitis B (HBV) ranges in severity from a mild illness lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver disease or liver cancer.

Hepatitis C (HCV) infection sometimes results in an acute illness but most often becomes a chronic condition that can lead to cirrhosis of the liver and liver cancer.

Hepatitis D (HDV) relies on HBV to replicate. It is uncommon in the United States.

Hepatitis E (HEV) usually results in an acute infection but does not lead to a chronic infection. Rare in the United States, hepatitis E is common in many parts of the world.

While there are vaccinations for hepatitis A and B, there currently are no vaccinations available for hepatitis C, D and E.

Dr. Mailliard says that about 5 percent of all adult urban men have hepatitis C. “Most patients have few if any symptoms,” he says. “The diagnosis is frequently made in the evaluation of hepatitis of unknown origin, or in patients with certain risk factors, including drug use.”

The medical center has an extremely active hepatitis C program. “We are probably the biggest prescriber of anti-virals for hepatitis C in a four-state area,” Dr. Mailliard says.

There are two clinical trials underway at the medical center in the use of hepatitis C protease inhibitors: telaprevir, developed by Vertex Pharmaceuticals Inc. and boceprevir, developed by Schering-Plough.

“Utilizing these groundbreaking, landmark medications, we are developing ‘second-wave’ therapy, with the first wave being pegylated interferon and ribavirin,” Dr. Mailliard says.

“Even with the combination, we can only achieve efficacy of about 40 percent. We hope to get that number up to 70 percent with the second wave.”
Mark Mailliard, MD

Interferon helps to stop HCV from making new copies of itself. It also helps the immune system to kill HCV. Pegylated interferon helps the drug stay in the body longer. It is injected once a week, while interferon that is not pegylated needs to be injected at least three times a week. Research indicates it is much more effective to treat HCV using a combination of pegylated interferon and ribavirin.

“Even with the combination, we can only achieve efficacy of about 40 percent,” Dr. Mailliard says. “We hope to get that number up to 70 percent with the second wave.”

Mark Mailliard, MD

The liver disease clinic at The Nebraska Medical Center played a large role in the evaluation and treatment of about 60 of the 99 patients infected with hepatitis C during a breach in infection control at a Fremont, Neb., oncology clinic in 2000 and 2001. The care of these patients formed the basis of a medical journal manuscript co-authored by Dr. Mailliard.

“We found that the cohort of adult cancer patients receiving chemotherapy were more susceptible to complications and significant liver disease due to the infection of HCV,” explains Dr. Mailliard. “One patient ultimately received a liver transplant and several died from the liver disease – not from the cancer.”

Though not members of the liver transplant team, Dr. Mailliard and Kim Schultz, physician assistant, interview people who desire to be a donor in the living donor liver transplant program. “We talk about their physical and emotional motivation, and we discuss the risks,” says Dr. Mailliard.

The liver transplant program performs about 120 transplants a year, making it easily one of the 10 most active transplant programs of its kind in the nation, Dr. Sorrell says. The living donor portion of the program has accounted for 103 transplants. This transplant procedure involves transplanting a portion of the donor’s liver into the recipient patient. In time, both portions regenerate and grow into normal-sized livers, due to the liver’s remarkable capacity to regenerate and adjust its size to its host.

“Combined with our highly-dedicated, multidisciplinary team, we are able to offer innovative, highly-specialized procedures and achieve optimal patient outcomes.”
Jean Botha, MD

Living donor transplants make up only 5 percent of the total transplant volume. “You approach this procedure with a great deal of caution, because you’re dealing with two lives,” Dr. Sorrell says. “The only reason we do it is because of the organ donor shortage.”

The liver’s impressive ability to regenerate has led to a unique surgical procedure that was performed for the first time in Nebraska by Jean Botha, MD, surgeon and director of Hepatobiliary Surgery at The Nebraska Medical Center and associate professor of Surgery at UNMC.

Using procedures originally described in a medical paper by a group of French surgeons, Dr. Botha has employed a two-staged approach to removing liver cancer tumors. In this process, he removes all the tumors in one lobe of the liver, and then he allows the lobe to regenerate for six weeks to three months before removing the other lobe.

Jean Botha, MD

The groundbreaking surgery is one example of the wide range of effective treatment options for patients with tumors and cancers of the liver and gastrointestinal (GI) tract. Other advancements include portal vein embolization, where the blood supply to one side of the liver is blocked in order to encourage the other side to grow and regenerate. This allows larger portions of liver to be removed. Less invasive laparoscopic surgery for liver resections is another advancement.

Dr. Botha emphasizes that the liver cancer team takes a multidisciplinary approach to all types of liver tumors by involving surgeons, hepatologists, radiologists and medical oncologists.

Patients with liver tumors also benefit from two new clinics at The Nebraska Medical Center, a specialty clinic for liver cancer and a separate clinic for metastatic carcinoid and other neuroendocrine tumors. These are tumors that usually arise from the gastrointestinal tract or pancreas and because of their propensity for slow growth become prime candidates for radical surgery.

“These clinics have been in the works for some time and are finally coming to fruition,” Dr. Botha says. “Combined with our highly-dedicated, multidisciplinary team (coordinated by gastroenterologist Fedja Rochling, MD), we are able to offer innovative, highly-specialized procedures and achieve optimal patient outcomes.”

Margaret Piper with Dr. Sorrell

Dr. Sorrell has been a leader throughout 37 years of liver disease study and treatment.

He received his medical degree from the University of Nebraska College of Medicine in 1959. After six years of general practice in Tecumseh, Neb., he returned to the University of Nebraska College of Medicine to complete a residency in internal medicine and a fellowship in gastroenterology. From 1967–71, Dr. Sorrell was at the New Jersey College of Medicine and completed a traineeship in hepatic disease and nutrition.

In 1971, he returned to Omaha to serve as assistant professor of internal medicine at UNMC, and to initiate and serve as the director of the Liver Study Unit, a joint venture of UNMC and the Veterans Administration Medical Center.

Through the years, the Liver Study Unit grew into a comprehensive program. It incorporated researchers, including biochemist Anthony Barak, PhD, and Dean Tuma, PhD, Dr. Sorrell’s research partner for 30 years. Other key physicians include: Rowen Zetterman, MD, now dean of the Creighton University School of Medicine; Byers “Bud” Shaw, MD, who co-founded the liver transplant program, the fourth of its kind in the nation, and until recently served as chairman of the Department of Surgery at The Nebraska Medical Center; Alan Langnas, DO, director of the liver transplant program; and Timothy McCashland, MD, the current medical director of the liver disease program.

“The list of surgeons, physicians and other medical professionals is a great indication as to why we have become nationally and internationally recognized,” says Dr. Sorrell, for whom the new UNMC Center for Health Science Education is named. “We have been fortunate to recruit the kind of professionals who viewed the study of liver disease with excitement and fascination.

“All this has combined to create a tremendous amount of intellectual ferment for research and enhanced the reputation of the university and the hospital. There isn’t anywhere you can go in the world where there is a group of liver experts who don’t know about Nebraska and our program. It took a lot of people to make that happen.”

It also took a great number of patients willing to take part in clinical trials or undergo new surgical procedures. Patients like Margaret Piper.

“Margaret is the sort of person who makes all this worthwhile,” Dr. Sorrell says. “She came to me with a rare disease seen almost exclusively in women, an inexorably progressive disease that I treated her for before we even started the liver transplant program.

“She was admirable in spirit and very self sufficient. I remember before she underwent the transplant, she broke her hip when she fell out of a tree while she was picking cherries.

“The liver transplant she received has allowed her to see her children grow up, get married and start producing grandchildren.”

Margaret with her great-granddaughter, Brooklyn

Fourteen grandchildren, to be precise, and nine great-grandchildren. “So I’m pretty busy, keeping up with ball games and swim meets,” Piper says.

She also went back to college, and in 2005 she obtained a degree in business technology and management from Peru State College. She volunteers at her daughter’s floral shop in Auburn, using the computer to keep business records.

And, every Monday as she has for the past 40 years, she types all the news into the weekly Brock Bugle, an eight-page publication that is eagerly anticipated and well-read in the community of 140 people.

At 74 years old, Piper still takes anti-rejection drugs 22 years after her transplant, “But it’s low dosage now; boy, it doesn’t cost near what it used to,” she says.

She attends annual reunions of transplant patients in Omaha. After writing thank-you letters that were forwarded each year by the hospital to the family of her liver donor, about three years ago she finally got to meet the family of the young boy whose liver she received.

“All these years, all I knew was that it had come from a little boy,” says Piper. “Because of my size (Piper weighs about 100 pounds), I needed a child’s liver.”

She now meets with the family at the transplant reunions, sharing stories – and her fondness for Dr. Sorrell.

So many sick people have come along since me and benefitted from all this knowledge and skill. And I can tell everyone, ‘I was number 62.’”

“I absolutely think the world of Dr. Mike and his wife, Shirley,” says Piper. “I had my surgery early on Sunday morning. He was there, went home and then he and Shirley came to the hospital to see me – both of them. Isn’t that something?”

Looking back, Piper says her strong religious beliefs and the expertise of the physicians, nurses and others who cared for her combined to give her life when all she had been able to contemplate was death.

“I have a very deep faith in the Lord, and so many years ago, I put myself in His hands,” Piper says. “After that, I was never afraid. I had absolute, complete confidence in my doctors. I had to. A transplant was my only option. I knew I was going to die without it.”

Next article in the Spring | Summer 2009 issue of One Thousand And One:
Restoring Faith