or Rhonda Smith, it all began 28 years ago. At the age of 20, a near-fatal car crash put her in a coma for a week. Her doctors were doubtful that she would survive, but after multiple blood transfusions and a three-month hospital stay, she pulled through. And for the next ten years, Smith (M.S.N. ’87) was certain that her dance with death was over. Then in 1984, she was diagnosed with hepatitis C. Prior to 1990, there was no identifying marker for hepatitis C, thus no way to ban it from the blood bank. Tens of thousands of people a year contracted what was called “non-A, non-B hepatitis” through intravenous drug use, blood transfusions, sexual encounters, and other blood-to-blood contact. Transmission rates peaked during the notorious 1960s and 1970s at around 170,000 new cases per year. Discovery and refinement of the hepatitis C marker eradicated the virus from the blood bank by 1992, but today there are up to 4 million people in the United States with the liver-attacking disease, many of whom don’t even know they are sick.

Hepatitis C, four times more prevalent than HIV, differs from versions A and B in many ways. Hepatitis A spreads through casual contact but is easily resolved. Hepatitis B spreads through sexual contact and blood-to-blood exposure more easily than C, but risk factors are similar for both. Hepatitis B is less likely than C to result in chronic infection because it often triggers an aggressive response from the immune system that helps thwart the invader. Jaundice is a sign that a person is fighting the virus and may ultimately clear the disease with help from drug therapy.

In contrast, hepatitis C is a master sleuth. It evades the body’s immune system by changing its own molecular configuration. To make matters worse, those molecular mutations occur within six different categories of hepatitis C. The most common category in the United States is genotype 1, also the most resistant to current treatment. As a result, about 85 percent of patients develop chronic infection. There are vaccines for hepatitis A and B, but the chameleon-like C remains an immunization conundrum.

ave you been vaccinated against B?” scowls Eugene Schiff, chief of the division of hepatology and director of the Center for Liver Diseases at the University of Miami School of Medicine, whose pseudo-gruffness quickly melts into a warm smirk. “You’re married, which makes you not as high a risk, but you can get B other ways too. People have cut themselves on things that other people have cut themselves on. I mean it! Get vaccinated against B, and get A while you’re at it!”

Schiff, who has been treating Rhonda Smith since 1984, is one of the world’s foremost experts on diseases of the liver. Following in the footsteps of his father, Leon, founder of the American Association for the Study of Liver Diseases, Eugene Schiff has just completed his term as the organization’s 51st president. At the School of Medicine, he conducts and oversees a heady batch of clinical trials, many of which have parlayed into pharmaceutical licensures and current standards of care. He is the editor of Schiff’s Diseases of the Liver, a veritable bible in the field and a former father-and-son venture now in its ninth edition. He served on the Advisory Committee on Blood Safety and Availability from 1997 to 1999, appointed by University President Donna E. Shalala while serving as secretary of Health and Human Services, and his expertise is regularly sought by the NIH, the CDC, and researchers all over the world.

But to his patients, Schiff is a true comrade in the struggle for health, a remarkable source of strength, support, and levity.

“I think that really one of the most beneficial things for me was Dr. Schiff. He was always available to me,” says Smith, whose tale spans the journey between devastation and jubilation.

Smith, a nurse practitioner for the past ten years at the UM/Jackson Blood and Marrow Transplant unit, at first thought the palpitations and exhaustion she was experiencing were heart-related. A blood work-up at the cardiologist’s office revealed sky-high liver enzymes. Referral to Schiff and subsequent liver biopsy confirmed the diagnosis of non-A, non-B hepatitis. She immediately began treatment with interferon, a protein normally produced by the body to help fight viral infection. Three times a week for a full nine years, Smith injected herself with this drug that has insidious side effects such as flu-like aches, chills, and sweats; extreme fatigue; loss of libido; and suppression of blood platelets and white blood cell count. In some people, interferon also causes severe depression and loss of appetite.

“There were many, many times,” Smith recalls, “taking that needle and getting ready to stick myself I said, ‘Why am I doing this? Why am I making myself sick with a drug that I’m not even sure what it is?’ But I just followed Dr. Schiff. I heard him in the background: ‘You can do it, you can do it, you can do it.’ He was always very supportive, and he was always there.”

Nine years of battling these symptoms caused by a drug that is only 20 percent effective in curing hepatitis C is incomprehensible to most people. But Smith explains that side effects with interferon were minimal compared to what she experienced taking interferon combined with ribavirin, a drug that doubles the efficacy of interferon alone. The fatigue became unbearable, and Smith almost reached the breaking point. Again, Schiff coaxed her back from the edge and helped her complete the full six-month combination therapy. The current standard of care—ribavirin plus interferon—is 55 percent effective in curing the disease. Virtually no gain is without sacrifice, however, and a serious side effect of ribavirin is loss of hemoglobin, further exacerbating the already debilitating exhaustion.

In many cases, drug side effects are far worse than the actual symptoms of the disease. In fact, many hepatitis C patients are asymptomatic; they may stumble upon their diagnosis through routine blood work or when they attempt to donate blood. But if left untreated, hepatitis C can lead to cirrhosis or even cancer of the liver. It is the leading cause of liver transplants in the United States, although virtually all transplant patients become reinfected with hepatitis C.

As it turns out, Smith’s hepatitis C was genotype 2, the kind that is about 80 percent curable with combination therapy. She is now celebrating her third year of freedom from hepatitis C, the milestone at which it is certain the disease will not return. Long-term use of interferon destroyed Smith’s thyroid, and now she takes Synthroid. “That’s perfect,” she says. “I can do a pill a day and have no hepatitis.”

hen patients come to see me for the first time, it’s not unusual for somebody to say, ‘When am I getting my liver transplant?’” says Schiff, noting that there are a lot of misconceptions about how hepatitis C should be treated. “In the spectrum of severity, we have cirrhosis at one end. But at the other end, we have about 30 percent with a really mild chronicity and, if you did nothing, the disease would probably never impact their life expectancy.”

Considering drug side effects, the trick is to weigh disease severity with lifestyle factors to determine when treatment is necessary. Hepatitis C-positive health care workers, for example, should be treated to lower their viral load and reduce the chances of accidentally transmitting it to their patients. Rhonda Smith is currently providing emotional support to a Boston cardiologist who contracted the disease from a positive patient during surgery. Referred to her by one of her former colleagues, the surgeon gains empathy and insight from her experience. Hepatitis C is much easier to contract following accidental needle stick than HIV, but the risk for health care workers is still relatively low compared to that of intravenous drug users.

Outside the health care arena, hepatitis C is virtually impossible to catch through casual contact. It is very unusual for the spouse of someone who is positive to contract the disease. The big no-no’s include sharing razors, toothbrushes, or anything that might carry particles of blood.

“Unfortunately, I tell people with hepatitis C to not tell anybody,” Schiff says. “They’re no threat to anybody. If they’re eating a sandwich and somebody took the sandwich from them and took a bite, nothing’s going to happen to them. When they tell people, unfortunately they’re treated as a leper.”

Part of the stigma comes from fear that people with hepatitis C are contagious. The other part comes from the all-too-common assumption that people with hepatitis C are drug users. In reality, the largest group of hepatitis C patients in this country may have experimented with drugs in their teens, but now they’re between 40 and 55 years old. “We’re not talking about heroin addicts,” Schiff says. “We’re talking about a group of people right now who, some 30 years later, are Mainstream America.”

For these patients, the majority of whom have genotype 1, the most insidious kind, therapies must improve. Schiff’s team of physicians and researchers at the Center for Liver Diseases, one of only a few centers in the country dedicated to the study and treatment of liver disease, has been conducting clinical trials. “Now scientists are looking at antiviral therapies that are specific for hepatitis C,” Schiff explains.

Unlike interferon and ribavirin, which have general antiviral and immuno-boosting effects, new strategies hone in on specific sites on the hepatitis C virus (HCV). One example is Heptazyme, manufactured by Ribozyme Pharmaceuticals, Inc. Heptazyme is designed to bind to HCV at the entry site for ribosomes, cell structures that are required for virus replication, then split the virus like a scissors. Phase II clinical trials are under way at the Center for Liver Diseases, one of five research sites nationwide.

Lennox Jeffers, a professor at the School of Medicine, also plays a critical role in advancing clinical knowledge about hepatitis C. Jeffers, chief of hepatology and director of the Center of Excellence for Hepatitis C at the Miami Veterans Affairs Medical Center, studies the disease in the veteran population. Between 10 and 15 percent of U.S. veterans are infected with HCV, which is a much higher prevalence than in the private sector.

“The epidemic of hepatitis really began with Vietnam-era veterans,” Jeffers says. “It’s just a matter of the times they lived in—the sixties—where exposure to drugs was much more common.” Others, he says, were infected through duty-related blood transfusions or exposure to blood on the battlefield.

As director of the Center of Excellence, a new program in which the Miami VA was first to participate, Jeffers helped pioneer treatment guidelines for interferon and ribavirin combination therapy. The three-year term, which Miami shared with the San Francisco VA, ends this year. Research continues full throttle with a groundbreaking $8 million NIH trial in which the Miami VA is one of eight sites comparing African-American to Caucasian veterans for response rates to interferon and ribavirin. Jeffers notes that about one-third of hepatitis C-positive veterans are African-American.

According to Schiff, the University of Miami is among the top four out of about 120 liver transplant centers in the United States, performing some 200 transplants a year. In the VA system, there are a total of only four centers, and none are in Florida. Jeffers, who trained as a hepatology fellow with Schiff 20 years ago, would like to see the Miami VA partner with UM/Jackson to become a designated VA liver transplant site. As it is, patients of the Miami VA benefit from its relationship with the University’s Center for Liver Diseases because, unlike veterans at other centers, they may be eligible for private sector clinical trials.

Jeffers recalls that he and Schiff were one of the first groups in the United States to send hepatitis C serum samples to Michael Houghton at Chiron Laboratories, the person who discovered the marker for the virus.

“Twenty-four hours after it made news that the hepatitis C virus was discovered, I was on the phone with Dr. Houghton,” Jeffers says, recalling one of the most exciting moments in his career. Jeffers notes that at the time, South Florida had a particularly high prevalence of hepatitis C due to the influx of Cuban refugees who had contracted it through vitamin injections while in Cuba.

he ultimate goal, of course, is a vaccine. The challenge is finding a formula that’s protective against all the variations. Studying HCV on the basic science level has its own set of obstacles. For one, hepatitis C occurs only in primates, making it difficult to study in animal models. And although HCV is nearly impossible to cultivate in the lab, Glen Barber, associate professor of immunology and microbiology at the School of Medicine, has found a way. His research team has spliced portions of HCV into another virus called VSV, which replicates “like wildfire” when introduced into mammalian cells. But the HCV produced in this way has no genetic material and is therefore harmless.

“It’s a bit like having two cars that look identical, but one has an engine and the other does not,” Barber explains.

Barber is evaluating mice that have received purified HCV, separated from its VSV host. The data is still coming in, but so far he says there’s been evidence of T-cell and antibody responses in the mice. “We’ve pioneered a lot of this stuff—using VSV as a vehicle to manufacture difficult-to-produce proteins that essentially we can use for vaccines and therapeutics. A lot of people are interested.”

Right now, there is some crossover between research at the clinical and basic science levels at the University, but more interaction is needed. “The idea is to liaison very tightly to get these basic science research findings from the lab examined and translated to the clinic as soon as possible,” Barber says.

Currently the Center for Liver Diseases spans multiple buildings and facilities campus-wide. The new Schiff Liver Institute promises to accelerate the bench-to-bedside path by placing basic science, clinical research, and patient care all under one roof. The institute will occupy 30,000 square feet of space on two floors in the Coulter Pathology Sciences building, a new four-story edifice slated for completion in 2004 or 2005.

“It will serve as a magnet for people interested in studying liver disease or who have liver disease,” Schiff says. “In other words, we’re going to advance the science of hepatology and the management of patients with liver disease.”

This is good news for the millions of people with hepatitis C who, unlike Rhonda Smith, still battle the tribulations of current treatment limitations.

“It has been an interesting ride, the ups and downs,” Smith reflects. “But I really believe that you’ve got to have family support and the understanding of the people you work with. Some people stop the treatment, saying they can’t do it, it’s too hard. My heart goes out to them. After I had realized that I had to go through this treatment—because I didn’t want any further damage to happen—then came a determination to conquer it. And we did.”