Perspective: preventive isoniazid therapy and the liver.

Area of Science:

• Public Health
• Infectious Disease Epidemiology
• Pharmacovigilance

Background:

• The preventive use of isoniazid (INH) for tuberculosis (TB) has been debated since 1975, with ongoing advocacy by official agencies despite conflicting cost-effectiveness and risk-benefit analyses.
• Previous studies on INH prophylaxis show a trend towards downplaying its hepatotoxicity and overlooking the decrease in TB incidence and mortality in regions without widespread INH adoption.

Observation:

• This review highlights three fatal cases of isoniazid-associated hepatitis, underscoring that this severe complication remains a significant concern with preventive INH use.
• The risk-benefit profile is unfavorable for compliant adults and older children with low TB risk, who are exposed to potentially fatal hepatitis.
• Conversely, INH therapy is challenging to administer effectively to high-risk populations such as individuals with alcohol or drug addiction.

Findings:

• Current widespread recommendations for preventive INH therapy are deemed unwise due to the disproportionate risk of fatal hepatitis.
• The study challenges the minimization of INH hepatotoxicity in risk-benefit assessments.
• There's a critical need to re-evaluate the declining TB rates in non-prophylaxis countries.

Implications:

• Health departments and medical practitioners should significantly limit the prescription of preventive INH therapy.
• A reassessment of current TB prevention strategies focusing on targeted, high-risk groups is warranted.
• The findings necessitate a more cautious approach to INH prophylaxis, prioritizing patient safety and addressing the actual burden of disease.