Latent TB treatment a greater risk to older adults

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Older adults treated for an inactive tuberculosis infection may be at increased risk of suffering liver damage from the medication, a study published Monday suggests.

Canadian researchers found that among all Quebec residents treated for so-called latent tuberculosis (TB) over six years, those older than 65 were more likely to be hospitalized for liver damage.

Overall, 2.6 percent of the treated older adults were hospitalized, compared to 0.2 percent of those in the same age group who were not treated for latent TB, the authors report in the Canadian Medical Association Journal.

The findings, researchers say, suggest that doctors need to carefully weigh the pros and cons of treating latent TB in people older than 65.

TB is a serious, potentially fatal bacterial infection that primarily attacks the lungs. The bacteria, called Mycobacterium tuberculosis, are spread through the air from person to person.

In most people, the immune system is able to suppress the bacteria from growing and spreading; these individuals do not become sick and they cannot spread the infection to anyone else. The TB bacteria do, however, remain in the body in an inactive state—what doctors call a latent infection.

In some cases, latent TB can become active. At particular risk are people with significantly weakened immune systems—from HIV, for instance, or certain immune-suppressing drugs used to treat cancer or autoimmune disorders like rheumatoid arthritis and Crohn’s disease.

People at high risk of developing an active infection may be offered TB treatment, which usually means six to nine months of a drug called isoniazid.

Liver damage is a known side effect of the drug. But until now, no large studies had looked at how often latent TB treatment causes serious liver problems in the general population.

“The main goal of this study was to quantify the risk,” said lead researcher Dr. Benjamin A. Smith, of McGill University in Montreal. “We were able to get a real-world picture, so we can give meaningful information to patients.”

According to Smith, the findings suggest that with older adults, the risk of latent TB reactivation needs to be carefully weighed against the risk of liver damage from treatment.

“By definition, people with latent TB are well,” Smith said. “So you want to try to be sure that the benefits outweigh the risks before you treat.”

The picture can get complex, he noted. Along with the main risk factors for TB reactivation—like chemotherapy and HIV infection—there are some other conditions that can contribute. Diabetes and advanced kidney disease, for example, have effects on the immune system that could raise the odds of the TB bacteria becoming active.

Those conditions, which are quite common in the elderly, are relatively minor risk factors for TB reactivation, however.

“If you have someone who is 20 years old, you’re going to be much less concerned about liver damage. So you’re probably going to treat if they have diabetes, or any other risk factor,” Smith said. But with someone older than 65, he added, “it gets more complicated.”

The findings are based on government health records for Quebec’s 7.7 million residents. Between 1998 and 2003, a total of 9,145 residents were treated for latent TB. Smith and his colleagues matched each of those individuals with records from two people the same age and sex who were not treated for the infection.

Of all the people treated for latent TB, 45 ended up being hospitalized for liver damage. The diagnosis was typically non-infectious hepatitis—liver inflammation not caused by a viral infection.

Adults older than 65 accounted for 22 of those 45 hospitalizations.

Older adults treated for latent TB were, not surprisingly, in poorer overall health than the comparison group. But even when the researchers accounted for medical conditions like cancer, diabetes and kidney disease, those treated for latent TB were still six times more likely to be hospitalized for liver damage than untreated older adults.

There was also a slightly higher rate of hospitalizations among 36- to 65-year-olds treated for latent TB, compared with those of the same age who were uninfected. But when other health problems were considered, the treatment itself was not clearly linked to increased risk.

The bottom line, according to Smith, is that older people diagnosed with latent TB should talk with their doctors about all the potential risks of treating, or not treating, it. One option could be to treat, and do monthly liver-function tests to detect any signs of damage early.

“It always boils down to the risks versus benefits for any one individual,” Smith said.

An estimated one-third of the world’s population carries latent TB, with it being most common in places like Russia, India, China, sub-Saharan Africa and parts of South America. In the U.S., an estimated 10 million to 15 million people have latent TB.

In Canada and the U.S., latent cases are typically detected when a person thought to be at risk of active TB undergoes a skin or blood test for the infection. That may be done when the individual has been exposed to someone with known or suspected TB, has risk factors for progression to active TB or is from a country with a high prevalence of TB.

SOURCE: CMAJ, online January 10, 2011.

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