WASHINGTON — A fifth patient who had developed a severe adverse reaction to an experimental drug for chronic hepatitis B during a government-sponsored clinical trial died early Tuesday morning.
Patient 6, as she was known by her identifying code, was the only woman in a 15-person study of the drug fialuridine, known as FIAU. She died of multisystem failure, including a severely inflamed pancreas and systemic infections, said Dr. William C. Stevenson, director of liver transplantation at the University of Virginia Health Sciences Center.
The 37-year-old woman had received two liver transplants, on July 9 and Aug. 14, and the second transplanted liver was functioning until her death, officials said.
The trial of FIAU, which had been considered a promising treatment for the devastating liver ailment, was halted in late June after several patients became seriously ill. A third of those who received FIAU in the most recent study since have died as a result of serious medical problems that developed from its use.
Hepatitis B, which is caused by a virus, is regarded as a significant global problem. The ailment is believed to infect an estimated 300 million people worldwide--5% of the population--primarily in Africa and Asia, particularly China.
In the United States, about 300,000 new cases of infection are reported annually and 1 million people are believed to be carriers. It is transmitted primarily through blood transfusions, sex and sharing contaminated hypodermic needles.
While not immediately life-threatening, hepatitis B can shorten life by decades and often lead to scarring of the liver, called cirrhosis, and liver cancer. There are no effective treatments for the disease.
The University of Virginia was not involved in the drug study, which was conducted by the National Institutes of Health, but most of the patients who suffered severe liver damage were referred to the university because it is one of the few medical facilities on the East Coast that regularly performs liver transplants on individuals with chronic hepatitis B infection.
The drug, manufactured by Eli Lilly & Co., had been studied previously in humans but never for longer than a month. The latest study was designed to test the drug's impact on hepatitis B during a six-month treatment period and was planned to include a total of 24 patients.
By the time the study was stopped, 10 participants had taken the drug for periods ranging from 67 to 90 days, in addition to the earlier four weeks of therapy. The other five had taken it for one month, including one who had participated in an earlier four-week study.
The patients who became ill were suffering from severe lactic acidosis, a condition that results when the liver is unable to remove lactic acid, a waste product, from the body.
Researchers now believe that the drug disrupts the genetic workings of the mitochondria, the subunits of cells where energy is produced, and cripples their ability to make new mitochondria. The mitochondria in the liver apparently were the most severely damaged, although multiple organs were involved. Liver cells are among the most difficult for the body to repair, which is why the patients were given transplants.