Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorASST Fatebenefratelli Sacco
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial population
Study participants will be adults being treated for TB or LTBI at the Department of Infectious Diseases at Luigi Sacco Hospital in Milan, a regional referral center for TB management. The population includes individuals treated both inpatient and outpatient settings, whose clinical, laboratory, imaging, microbiological, and treatment data were routinely collected as part of standard care. The study comprises two sources: a retrospective cohort of adults treated with isoniazid between 2020 and 2025 and a prospective cohort enrolled between 2026 and 2028. Together, these groups represent the real-world patient population managed at this center for the treatment of TB and LTBI.
Trial design
Design model
Cohort
Time perspective
Other
Treatments tested in this trial
Standard isoniazid-based TB/LTBI therapy
Other interventionIsoniazid administered as part of routine tuberculosis or latent tuberculosis infection treatment, according to standard clinical guidelines. The study observes real-world outcomes and does not assign or modify therapeutic regimens.
Treatment groups
220 Participants
are divided into 1 treatment groupGroup A: INH-treated Cohort1 intervention
Trial outcomes
Primary outcomes
1
Incidence of isoniazid-induced hepatotoxicity in adults treated for TB or LTBI
Proportion (%) of participants developing hepatotoxicity during treatment with isoniazid, defined according to international DILI criteria (ALT \>5× ULN and/or bilirubin \>3x ULN or ALT \>3× ULN and/or bilirubin \>2x ULN with symptoms). Unit of measure: Percentage of participants (%)
Time frame
From treatment initiation to end of TB/LTBI therapy (approximately 6 to 12 months).Secondary outcomes
1
Risk factors for isoniazid-induced hepatotoxicity
Identification of demographic, clinical, microbiological, and lifestyle factors associated with isoniazid-induced hepatotoxicity, including comorbidities (e.g., HIV infection and systemic diseases). Associations will be evaluated using multivariable regression models and reported as odds ratios with 95% confidence intervals. Unit of measure: Odds Ratio (OR)
Time frame
During isoniazid treatment and up to 12 months after treatment initiation.2
Time to biochemical recovery after hepatotoxicity
Time from the onset of isoniazid-induced hepatotoxicity to normalization of liver enzyme levels (ALT and bilirubin). Unit of measure: Time (days)
Time frame
Up to 6 months after hepatotoxicity onset3
TB or TBI treatment completion
Proportion of participants completing the planned TB or TBI treatment regimen despite the occurrence of hepatotoxicity. Unit of measure: Percentage of participants (%)
Time frame
At the end of TB/TBI therapy (approximately 6-12 months).4
Effect of corticosteroid therapy on biochemical recovery
Comparison of time to biochemical recovery between participants with hepatotoxicity treated with corticosteroids and those managed without corticosteroid therapy. Unit of measure: Time to recovery (days)
Time frame
Up to 12 months after hepatotoxicity onsetSponsors and contacts
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Source ClinicalTrials.gov
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