A Case of Evolving Hepatotoxicity Following Systemic Drug Reaction to Isoniazid-Rifapentine (3HP).

The 3-month, once-weekly regimen of isoniazid plus rifapentine (3HP) is widely used for latent tuberculosis infection (LTBI) because of its shorter duration and favorable adherence compared to isoniazid monotherapy. However, 3HP is associated with hepatotoxicity as well as systemic drug reactions (SDRs), characterized by rapid-onset flu-like symptoms, fever, myalgias, and rash, which may complicate therapy. We describe a healthy 26-year-old male diagnosed with latent tuberculosis who developed acute SDR symptoms accompanied by hepatotoxicity after his third dose of 3HP. The liver injury was initially cholestatic and evolved into a worsening hepatocellular pattern despite discontinuation of 3HP, with gradual normalization over 4 weeks. Autoimmune serologies were briefly positive but resolved spontaneously without intervention. This case illustrates the potential for SDRs with evolving liver injury during 3HP therapy and underscores the importance of early recognition of adverse effects and individualized management.