Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors (INH-DILI)

ASST Fatebenefratelli Sacco

Status: Begins enrollment in 1 month

Conditions: Tuberculosis Infection; Tuberculosis Infection, Latent

Treatments: Other: Standard isoniazid-based TB/LTBI therapy

Study type: Observational

Funder types: Other

Identifiers

NCT07472348

INH-DILI-2025

Details and patient eligibility

About

The objective of this observational study is to determine how frequently isoniazid (INH) causes liver injury (hepatotoxicity) in adults treated for tuberculosis (TB) or latent tuberculosis infection (LTBI) and to understand which factors increase this risk. The study also aims to describe how hepatotoxicity is managed in real-world clinical practice and whether treatments such as corticosteroids can improve liver function tests.

The main questions this study aims to answer are:

• How frequently does INH-induced hepatotoxicity occur in adults treated for TB or LTBI?
• What demographic, clinical, microbiological, or lifestyle factors increase the risk of developing hepatotoxicity?
• How do different management strategies, including treatment modification or the use of corticosteroids, affect liver recovery and completion of TB/LTBI therapy? This study does not involve experimental treatments. Researchers will analyze information already collected during routine clinical care, both retrospectively (from 2020 to 2025) and prospectively (2026-2028). There is no comparison group, but participants may have different clinical profiles or treatments, which will be compared to understand risk factors and outcomes.

Participants will:

• Receive standard treatment for tuberculosis or LTBI, including isoniazid, as prescribed by their treating physicians.
• Undergo routine assessments, such as blood tests, microbiology, imaging, and clinic visits, as part of their regular care.
• Their clinical data will be recorded in the study database to analyze liver function trends, treatment changes, and outcomes.

The study will contribute to improving understanding of INH-induced hepatotoxicity and supporting safer and more effective treatment strategies for tuberculosis and LTBI.

Full description

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

220 participants in 1 patient group

INH-treated Cohort

Description:

Adults (≥18 years) diagnosed with tuberculosis (TB) or latent TB infection (LTBI) who received isoniazid as part of their standard treatment regimen. This cohort includes both retrospective participants (treated between 2020-2025) and prospective participants (2026-2028). No experimental interventions are administered; all treatments follow routine clinical care.

Treatment:

Other: Standard isoniazid-based TB/LTBI therapy