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However, 3HP is associated with hepatotoxicity as well as systemic drug reactions (SDRs), characterized by rapid\u2010onset flu\u2010like symptoms, fever, myalgias, and rash, which may complicate therapy. We describe a healthy 26\u2010year\u2010old 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\u2009weeks. 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.<\/jats:p>","DOI":"10.1155\/crhe\/2508892","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T03:13:54Z","timestamp":1764040434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Case of Evolving Hepatotoxicity Following Systemic Drug Reaction to Isoniazid\u2013Rifapentine (3HP)"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9877-6031","authenticated-orcid":false,"given":"Niels","family":"Vizgan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Martinez-Kratz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"LaBudde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0738-3991","authenticated-orcid":false,"given":"Fredric","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"e_1_2_8_1_2","volume-title":"Treatment for Latent Tuberculosis Infection","author":"CDC","year":"2025"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6901a1"},{"key":"e_1_2_8_3_2","article-title":"ATS\/CDC\/IDSA Clinical Practice Guideline: Treatment of Drug-Susceptible Tuberculosis. 2025 Update","author":"Saukkonen J. 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