Preventing Fungal Infections in People Who Get Liver Transplants

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The summary below is from the full report titled "Prophylactic Fluconazole in Liver Transplant Recipients. A Randomized, Double-Blind, Placebo-Controlled Trial." It is in the 16 November 1999 issue of Annals of Internal Medicine (volume 131, pages 729-737). The authors are D.J. Winston, A. Pakrasi, and R.W. Busuttil.

What is the problem and what is known about it so far?

Infection is a major problem for people who get liver transplants. Infections with fungus are a particularly big problem. Fungal infections can be hard to treat and potentially deadly. It may make sense to try to prevent them from happening in the first place.

Why did the researchers do this particular study?

The researchers wanted to see if giving liver transplant patients an antifungal medication called fluconazole could prevent them from getting fungal infections. They also wanted to make sure that using fluconazole this way would be safe for patients and would not cause damage to the new liver.

Who was studied?

212 patients who had a liver transplant at a transplant center in Los Angeles, California. Study patients had to be free of fungal infection at the start of the study.

How was the study done?

The researchers gave study patients either fluconazole or a placebo, starting the day before transplant surgery and continuing until 10 weeks after the surgery. A placebo is a something that looks, smells, and tastes like the active medicine but contains no active ingredients. This type of study is called a randomized, controlled trial, and each patient has an equal chance of receiving one of the treatments. Studies are designed like this when it is not clear that one treatment is better than another or better than no treatment at all. The researchers then followed all of the patients very closely, looking for fungal infections and for any side effects that could be due to the fluconazole.

What did the researchers find?

104 patients got placebo, and 108 got fluconazole. Proven fungal infections occurred in 45 of 104 patients on placebo and in only 10 of 108 patients on fluconazole. Fluconazole prevented both mild fungal infections (like infections of the skin) and serious fungal infection (like infections in the blood). However, patients on fluconazole were as likely to die during the study as were patients who got placebo. Fungal infection was less likely to be the cause of death for patients on fluconazole. Fluconazole did not seem to cause any liver damage in the patients who got it. However, patients who got fluconazole were more likely than patients who got placebo to suffer from such side effects as headaches, shakes, and even seizures. The researchers found that these side effects developed because the patients on fluconazole developed high levels of another medication, cyclosporine, which many liver transplant patients get. Fluconazole seems to change the way people handle cyclosporine so that lower doses are necessary to get the same blood levels of cyclosporine.

What were the limitations of the study?

While fluconazole does seem to prevent both mild and serious fungal infections in people who get liver transplants, it may not improve survival after this procedure. Larger studies would be necessary to see if preventive treatment with fluconazole may improve how patients do overall.

What are the implications of the study?

Fluconazole can decrease fungal infections for liver transplant patients, but it may not improve how they do overall. Patients who get fluconazole should have cyclosporine monitored very closely to make sure that they do not develop excessively high levels.