Publications

BACKGROUND

The frequency of isoniazid hepatotoxicity is low in children receiving isoniazid therapy for latent tuberculosis infection. However, isoniazid hepatotoxicity may cause liver failure and death. We evaluated children who developed isoniazid hepatotoxicity to determine demographic and clinical characteristics.

METHODS

A retrospective review was performed of medical records of 1582 patients aged <18 years who were evaluated for isoniazid therapy at a public health department and clinic in California.

RESULTS

There were 13 patients who had latent tuberculosis infection and who developed isoniazid hepatotoxicity (0.8% of all 1582 patients who started isoniazid; 1.1% of 1235 patients who completed the 9-month isoniazid therapy). There were 8 girls (62%) and 9 Hispanic children (69%) who had hepatotoxicity. Sex, age, and race were not independently associated with the development of isoniazid hepatotoxicity. Symptoms and signs of hepatotoxicity were present in 11 of the 13 patients, and 2 other patients had alanine aminotransferase >5 times the upper limit of normal and no signs of hepatotoxicity. The most common symptoms included abdominal pain, anorexia, vomiting, and nausea. Most patients developed hepatotoxicity within 6 months of starting isoniazid, but 3 patients developed hepatotoxicity ≥6 months after starting isoniazid. After stopping isoniazid, the alanine aminotransferase levels decreased to normal in all patients.

CONCLUSIONS

In children who have latent tuberculosis infection, isoniazid hepatotoxicity has low frequency and typically is reversible when isoniazid is stopped. Evidence of late drug-induced liver injury indicates the importance of monitoring symptoms and serum transaminases throughout isoniazid therapy.

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.