# 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

## TL;DR

This study highlights the liver damage risk of isoniazid in patients with autoimmune rheumatic diseases, especially when combined with other liver-harming drugs.

## Contribution

The study identifies specific risk factors for isoniazid-induced hepatotoxicity in immunosuppressed rheumatic disease patients.

## Key findings

- Hepatotoxicity occurred in 64 R-IMID patients on isoniazid, with 20.3% showing ≥4× upper limit of normal liver enzymes.
- Combining isoniazid with methotrexate or other hepatotoxic drugs significantly increased liver injury risk.
- Literature review showed INH-related hepatotoxicity rates ranging from 1–41% in rheumatic disease patients.

## Abstract

Background/Objectives: 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. Methods: 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. Results: Hepatotoxicity was frequent when INH was combined with other hepatotoxic drugs, especially methotrexate. Conclusions: 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.