Short-Course Treatment for Latent Tuberculosis Is Associated with More Frequent Liver Injury Than Long-Course Treatment Is

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The summary below is from the full report titled "Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Multicenter Clinical Trial." It is in the 15 October 2002 issue of Annals of Internal Medicine (volume 137, pages 640-647). The authors are RM Jasmer, JJ Saukkonen, HM Blumberg, CL Daley, J Bernardo, E Vittinghoff, MD King, LM Kawamura, and PC Hopewell, for the Short-Course Rifampin and Pyrazinamide for Tuberculosis Infection (SCRIPT) Study Investigators.

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

Tuberculosis is an infection that usually involves the lungs but can also affect other areas of the body. People can develop tuberculosis when exposed to someone with it, especially if the infected person is coughing. People exposed to tuberculosis do not always become sick. The tuberculosis bacteria can "hide out" in a person's body for many years—a situation called latent tuberculosis. Doctors can tell when patients have latent tuberculosis because they have positive tuberculosis skin tests but normal chest x-rays and no symptoms. Because latent tuberculosis can become active many years after exposure, doctors treat people with latent tuberculosis with antibiotics unless their age or medical history makes them at high risk for the side effects of treatment. The most common serious side effect of tuberculosis treatment is liver damage. Guidelines suggest three main treatment options for latent tuberculosis: 1) isoniazid for 6 to 9 months, 2) rifampin for 4 months, or 3) rifampin and pyrazinamide for 2 months. This last option is attractive because patients have to take drugs for only 2 months. Unfortunately, several reports of liver problems in people taking rifampin plus pyrazinamide have raised concerns about the safety of this treatment.

Why did the researchers do this particular study?

To find out whether liver damage is more common in patients treated with rifampin plus pyrazinamide for 2 months than in patients treated with isoniazid for 6 months.

Who was studied?

589 patients with latent tuberculosis who received treatment in one of three tuberculosis clinics in the United States.

How was the study done?

The researchers prescribed 2 months of rifampin plus pyrazinamide for all patients who presented to the clinics one week, isoniazid for patients who presented the next week, and so on until they had assigned treatment to 589 patients. They followed patients closely, checking blood tests of liver function.

What did the researchers find?

207 patients taking rifampin plus pyrazinamide and 204 patients taking isoniazid returned for follow-up. Of the 207 patients taking rifampin plus pyrazinamide, 54 developed some liver damage compared with 32 of the 204 patients taking isoniazid. Liver damage was severe in 16 patients taking rifampin plus pyrazinamide and in 2 patients taking isoniazid.

What were the limitations of the study?

This study could not identify patient characteristics that increase the risk for liver problems during therapy with rifampin plus pyrazinamide.

What are the implications of the study?

If patients and doctors choose to treat latent tuberculosis with 2 months of rifampin plus pyrazinamide, frequent laboratory tests of liver function should be done to screen for liver damage. If blood tests suggest liver damage, patients should stop taking the drugs.