Drug Cocktail Prevents Hepatitis B Virus From Recurring After Liver Transplant

Embargoed until April 29, 2002

Kirsten Holguin, [email protected](310) 794-0777

UCLA Retrospective Study Shows Drug Cocktail Prevents Hepatitis B Virus From Recurring After Liver Transplant

Aiming to prevent recurrence of the hepatitis B virus (HBV) in post liver transplant patients, UCLA researchers retrospectively reviewed survival rates of hepatitis B liver transplantation patients. Their findings show that a combination of two drug therapies improved patient survival rates when compared to existing drug therapies given alone -- and that long-term treatment dramatically decreases recurrence of the disease.

The results, published in the May issue of the Annals of Surgery, showed the viral prophylaxis therapy -- or preventive treatment of Hepatitis B Immune Globulin (HBIg) and lamivudine in combination prevents recurrence of HBV infection and lengthens patient survival rates following liver transplantation.

Researchers studied a total of 3,094 liver transplants performed at UCLA Medical Center from 1984 through April 2001. Of those, 191 transplant operations were performed on 166 patients afflicted HBV cirrhosis. The patients were divided into four treatment groups: no prophylaxis, lamivudine monotherapy, HBIg monotherapy or a lamivudine and HBIg combination.

When comparing the combination therapy to the monotherapy or no therapy, the HBV-free survival rates were considerably higher for patients who received the combination of HBIg and lamivudine. The one-year and three-year survival rates for the combination therapy were 92 percent and 81 percent, respectively. Survival rates for lamivudine alone rates were 72 percent and 62 percent. Patients given HBIg alone rates were even lower at 45 percent and 36 percent.

Researchers also considered what effect therapy duration might have in HBV recurrence. With short term HBIg monotherapy, HBV infection recurred in 60 percent of patients after transplant. With long term HBIg monotherapy, which is defined as greater than six months, 40 percent of the patients suffered HBV recurreence. But, patients receiving long term HBIg and lamivudine therapy had a dramatic reduction in the recurrence rate with an HBV infection rate of only 2.8 percent.

"Liver transplantation for hepatitis B with this drug regimen results in survival rates that are as good if not better than other indications to liver transplantation," said Dr. Ron Busuttil, UCLA professor and chief of the division of liver and pancreas transplantation, director of the Dumont-UCLA Liver Transplant Center. "This is truly remarkable since -- as recently as five years ago -- patients with hepatitis B were not even being considered for transplantation,"

Approximately 1.25 million people in the United States and 300 million people worldwide are chronically infected with hepatitis B. Chronic infection of hepatitis B often leads to end stage liver cirrhosis and the development of liver cancer with a liver transplant as the only treatment option for these patients. Without a transplant, five to six thousand people with chronic hepatitis B die each year in the United States.

In the past, liver transplantation for patients with HBV cirrhosis resulted in an 80 percent recurrence rate and poor patient survival. Many transplant centers did not consider HBV patients to be good candidates for transplantation and many insurance providers -- including Medicare -- denied reimbursement for a transplant for HBV patients.

Early strategies to improve the post transplant outcome for preventing recurrent HBV infection included perioperative HBIg treatment that, as mentioned, showed a survival benefit when administered long term but recurrence was still common. In 1996, lamivudine became available and was shown to prevent the hepatitis B virus from replicating. However, its effectiveness when used alone has been limited by the rise of resistant viral strains of HBV due to mutation.

This study also clearly demonstrates that HBIg and lamivudine when used in combination have a synergistic effect. That is, their effectiveness in preventing Hepatitis B is much greater when used together because they work in different ways to help the body clear the virus. This approach has been successfully applied in the treatment of other infectious diseases, such as the "drug cocktail" used for HIV. Since each drug targets the virus in a different way, it reduces the chance that a mutation will develop that renders the treatment ineffective.

The study was funded in part by the Dumont Foundation, the Torino Foundation and the Joanne Barr Foundation.

-UCLA-