Reprinted with permission from the October, 2004 issue of M.D. News, Baltimore-Annapolis edition.
The Comprehensive Liver Center at the University of Maryland Medical
by Martie Callaghan
Individuals suffering with liver disease of all types are finding many new and effective treatment options at the Liver Center at the University of Maryland Medical Center. The key words here are "all types." The diverse nature of liver disease demands a medical team equipped to move in many directions, never relenting, in search of the appropriate diagnosis and the best method of intervention in each individual case. The Center's comprehensive approach to liver disease embodies all of this.
"People from different departments come together to work on particular cases in the liver center," says Charles D. Howell, M.D., associate professor of medicine at the University of Maryland School of Medicine. "When caring for patients, we practice an interdisciplinary approach that brings to the patient the highest levels of expertise in all aspects of care for a certain disease, from early stages to the most advanced."
For these reasons, Benjamin Philosophe, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine; acting chief, Division of Transplantation; and director of Liver Transplantation and Hepatobiliary Surgery at the University of Maryland Medical Center, encourages area physicians to send their patients with liver disease to the University of Maryland. "We have expertise that is really very, very focused on the liver," he says. "This is unique and really not present in many community hospitals."
Liver cancer is the most common cancer in the world, according to William Regine, M.D., professor and chair of the Department of Radiation Oncology at the University of Maryland School of Medicine and chief of Radiation Oncology at the University of Maryland Medical Center. Secondary liver cancer accounts for the majority of cases, with the most common primary sites being the stomach, pancreas, breast and lung. "Ultimately, about one-third of all cancers spread to the liver," Dr. Regine says, "probably because the liver is a big filter organ where a lot of blood passes. If there are cancer cells in the body, they will get stuck in the liver."
Primary liver cancer, as well as cancer that has metastasized from the colon, can often be surgically removed. "I have seen many cases where a patient is treated for colon cancer and, six months later, a spot is found on the liver which can be of significant size," Dr. Philosophe says. "Unfortunately, in this scenario, the patient is often told that nothing further can be done. The reality, however, is that with advanced technologies, such as radiofrequency ablation, chemo-embolization, SIR-spheres, and surgical techniques, these patients can often be helped." For lesions in difficult spots, ex-vivo resections can be performed. This is a complex procedure, perfected by transplant surgeons, that involves removing the entire liver, taking out the tumor on a back table and sewing the liver back in the patient. "We can also combine a liver resection of one lobe with radiofrequency ablation of a lesion in the other lobe," Dr. Philosophe says. Radiofrequency ablation is a very localized treatment that kills the tumor with heat, while sparing the rest of the liver. Many patients who had been deemed terminal have had this treatment combination and, years later, remain free of cancer.
In the case of inoperable liver cancer, a revolutionary treatment called SIR-Spheres has emerged as a very promising treatment option. This finely targeted, internal radiation therapy uses millions of microscopic spheres injected into the liver, directly to the site of the tumor. The microspheres, one-third the diameter of human hair, are like polymer beads and contain the radioactive element, Yttrium 90. "The targeted nature of this therapy allows us to deliver up to 40 times more radiation to liver tumors than could be possible using conventional radiation techniques," says Dr. Regine. Treatment takes less than an hour and most patients go home within two to six hours. The beads remain in the liver and lose their radiation within two weeks. Generally, patients receive two treatments, four weeks apart. In 2002, the U.S. Food and Drug Administration approved SIR-Spheres for use in patients with primary colorectal cancer that has spread to the liver.
"SIR-Spheres is one of a wide range of targeted therapies that we offer at the University of Maryland within the context of a liver directed therapies program," says Dr. Regine. "Most people get seen by one specialist at a time. Here, we have pooled all of our tools together and you see us all. Our specialists meet together weekly and come up with a very tailored, sophisticated program for each liver cancer patient."
For patients with liver disease known as cirrhosis, lives are being saved through the Liver Transplantation Program at the University of Maryland. Patients who would otherwise die from end-stage liver disease are given a second chance here. However, the program is heavily reliant on the availability of organs and has reached a critical level where demand has exceeded supply. Patients with kidney disease can go on dialysis and even cardiac patients can benefit from an artificial heart, in order to buy time until an organ becomes available for transplant. "Not so with the liver," says Dr. Philosophe. "There is no bridge. If a liver is not found in time, the patient dies. In fact, in Maryland there are nearly as many people dying on the transplant list waiting for a liver as there are getting transplanted."
A patient who is fairly sick may not make it to the top of the waiting list in time for a liver transplant. In that case, a living donor, usually a family member, can be used. The diseased liver is taken out of the recipient and replaced with the right lobe of the donor's liver. That leaves the recipient with approximately 60% of a liver and the donor with 40%. Both liver segments will grow, however, although they technically do not regenerate the opposite lobe. "The donor operation is an extensive procedure to perform on someone who is perfectly healthy and does not need surgery," Dr. Philosophe says. "A living donor kidney transplant is a safer operation and can even be done with key-hole (laparoscopic) surgery. The donor gives up one kidney but does well with the remaining one. In contrast, for living donors, we have to cut the liver in half. Although we have had good success with this, it's a big surgery with a lot of potential complications."
Until about two years ago, the allocation of livers for patients on the transplant waiting list highly emphasized the amount of time a patient had been waiting. That system has been changed so that priority is now given according to severity of illness. Patients are placed on the list according to a calculation called the Model for Endstage Liver Disease (MELD), which uses a formula to predict the likelihood of a patient dying from the disease within three month's time. The higher the MELD score, the higher the spot on the list. "Let's say I evaluate a person in my office and find him to be fairly ill," says Dr. Philosophe. "Under the old system, he or she would probably die before getting transplanted, since the waiting time was fairly long. Under the new system, since priority is given to illness, a patient with a high MELD score can potentially jump to the top the minute they are listed. This new allocation system in a way has decreased the necessity for a family to pursue living donation as the only life-saving option for their loved one."
Nearly half of the 4,000 liver transplants in the United States each year are attributable to the hepatitis C virus. Dr. Howell, who became interested in transplant hepatology while in medical school at Baylor University, continues to focus on this research. He is currently the principal investigator at the University of Maryland in a study called VIRAHEP-C, sponsored by the National Institutes of Health. The purpose of this multi-center clinical trial is to find out why African-Americans who have the hepatitis C virus do not respond as well as whites to hepatitis C treatments. "This is the largest clinical trial in hepatitis C involving African-Americans," Dr. Howell says. "Hepatitis C is more prominent in African-Americans than in whites and appears to have worse outcomes in terms of higher incidence and death rates from liver cancer. Furthermore, African-Americans do not appear to respond as well to the available treatments."
Prior studies of patients diagnosed with the hepatitis C virus, genotype 1, have shown a combination therapy using interferon and ribavirin to be effective in 52% of Caucasian patients and only 32% of the African-American patients.
While the lower response rate in African-Americans may be partly due to their under-involvement in the research, it is expected that VIRAHEP-C will reveal more significant factors in the 200 African Americans and 200 Caucasians enrolled in the trial.
Other projects in which Dr. Howell is involved include a study of HCV genotype 2 and 3 patients to determine if a shorter treatment time is more effective. "Treatment side effects are hard for patients to tolerate," says Dr. Howell. "Six months has been the empirical time frame but we are now trying to decide whether these patients can experience equal results in 16 weeks compared to 24 weeks." In another study, researchers are looking at patients who failed prior treatment to see if higher doses for a longer period of time will be beneficial in clearing the virus. "We are trying to stay on the leading edge of new treatment development," Dr. Howell says. "The whole point of treatment is to prevent liver cancer, prevent liver cirrhosis and prevent the need for liver transplantation. We know that in people we treat for hepatitis B and C who have the desired response, we are able to prevent the progression of liver disease and are actually improving their long-term liver health."
Dr. Regine predicts that we will see the best of all worlds in future treatment of liver disease. "I think radiation oncology technology will continue to deliver more therapeutic doses of radiation while doing an even better job of sparing surrounding tissue," he says. "I think there will be a lot more selective internal radiation therapy and noninvasive therapy for liver cancer. Technology is evolving that can hone in on elements of a cancer cell that are truly specific to cancer tissue. In doing this, treatment delivery is getting more sophisticated, more targeted and more refined. You have to be optimistic in this business....