Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors

Isoniazid (INH) is an essential drug for the treatment of tuberculosis (TB) and latent tuberculosis infection (LTBI), but it can cause liver damage in a subset of patients. The onset of liver toxicity is often unpredictable and can lead to treatment interruptions, alternative regimens, or incomplete therapy. Despite the widespread use of INH, real-world data describing the incidence, clinical characteristics, and management strategies of INH-induced hepatotoxicity remain limited, especially in European clinical settings.

This single-center, observational study will analyze adults treated for TB or LTBI who received INH as part of their therapeutic regimen. It combines a retrospective cohort (2020-2025) and a prospective cohort (2026-2028), allowing for the evaluation of both historical and current clinical practices. Clinical information already collected during routine care, including demographics, comorbidities, microbiological and imaging findings, anti-TB treatment details, and serial laboratory data, will be used to characterize the development and course of hepatotoxicity.

The study aims to describe the presentation of hepatotoxicity, how it is managed in routine clinical practice, and how clinical decisions, such as modifying antituberculosis therapy or the use of corticosteroids, influence liver recovery and treatment completion. INH-induced hepatotoxicity will be defined using internationally accepted criteria for drug-induced liver injury. Management strategies, including the use of corticosteroids, will be analyzed to understand their impact on biochemical resolution, safety, and treatment outcomes.

Because this is an observational study, no experimental interventions will be administered. All treatments, tests, and clinical decisions will follow standard tuberculosis and LTBI care provided by Luigi Sacco Hospital. Data will be pseudonymized and collected via the electronic case reporting form. The study is expected to provide evidence that can help optimize treatment strategies and support future clinical trials focused on safer management of INH-related liver injury.

Inclusion criteria

• Adults aged ≥18 years.
• Patients diagnosed with TB or LTBI who received INH as part of their treatment regimen (either first-line or second-line therapy), regardless of combination with other anti-TB drugs.
• Normal baseline liver function tests (ALT, AST and bilirubin within reference range) and absence of clinical symptoms of liver dysfunction prior to initiation of anti-TB therapy.
• Signed informed consent.

Exclusion criteria

• Patients who did not receive isoniazid during their treatment course.
• Pre-existing liver dysfunction, including biliary origin, before anti-TB therapy.
• Pregnancy or lactation.
• Concomitant use of non-TB hepatotoxic drugs.
• Abnormal hepatic function on baseline laboratory testing.
• Known INH resistance at treatment initiation.
• Refusal to provide informed consent.