Hepatotoxicity Risk of Isoniazid in Patients with Autoimmune Rheumatic Diseases and Prior Liver Injury Due to Disease-Modifying Antirheumatic Drugs: A Single-Center Experience and Literature Review

<b>Background/Objectives</b>: Patients with rheumatic immune-mediated inflammatory diseases (R-IMID) require latent tuberculosis infection screening and, in case of positivity, chemoprophylaxis. Isoniazid INH remains the standard regimen, but hepatotoxicity is an underrecognized concern. To describe the characteristics of R-IMID patients developing hepatotoxicity during INH therapy and identify potential risk factors through clinical analysis and literature review. <b>Methods</b>: Retrospective study of 64 R-IMID who developed hepatotoxicity with INH. Mean age was 53.4 ± 10.5 years; 70.3% female. Diagnoses included spondyloarthritis/psoriatic arthritis (56.3%), rheumatoid arthritis (32.8%), systemic sclerosis (4.7%), connective tissue diseases (4.7%), and other IMIDs (3.2%). All patients showed ≥ 2 × upper limit of normality (ULN) liver enzyme elevation, 34.4% ≥ 3 ULN, 20.3% ≥ 4 ULN. Literature review (19 studies) revealed INH-related hepatotoxicity rates of 1-41%, exacerbated by concurrent methotrexate, sulfasalazine, TNF inhibitors, and prior drug-induced liver injury. <b>Results</b>: Hepatotoxicity was frequent when INH was combined with other hepatotoxic drugs, especially methotrexate. <b>Conclusions</b>: INH prophylaxis in R-IMID patients carries substantial hepatotoxic risk. Careful hepatic monitoring and individualized risk stratification are essential to prevent liver injury in immunosuppressed populations.