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Updated: Dec 30, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Dosing of Antimycotic Treatment in Sepsis-Induced Liver Dysfunction by Functional Liver Testing with LiMAx®
Carmen Kirchner1, Jasmin Sibai1, Elke Schwier2
1Department of General and Visceral Surgery, Thoracic Surgery and Proctology, Ruhr University Bochum, Klinikum Herford, Herford, Germany.
Background:
Sepsis-treatment is one of the major challenges in our time. Especially fungal infections play an important role in patient's morbidity and mortality. In patients with septic shock, liver function is often significantly impaired and therefore also hepatic drug metabolism is altered.
Case Presentation:
We report about a 56-year-old man suffering from invasive fungal infection with multiorgan failure, after complicated medical history due to symptomatic infrarenal aortic aneurysm. On the first postoperative day, a CT scan was undertaken due to massive back pain showing renal infarction on both sides. As qualitative and quantitative renal function was impaired, hemodialysis was started immediately. Subsequently, the patient developed a compartment syndrome of the left leg and underwent fasciotomy. On admission day 7, the patient presented with hematochezia leading to colonoscopy. During this procedure, an ischemic colitis was observed. As conservative treatment failed, the patient underwent Hartmann's procedure due to progredient ischemia followed by a worsening of the clinical status due to sepsis. The patient suffered from an invasive fungal infection with Candida spp. and Aspergillus spp. Systemic antifungal treatment was initiated. Although azoles are considered first-line treatment in these cases we chose the echinocandin caspofungin for its presumed lower impact on liver function compared to azoles like voriconazole or Amphothericin B. However, caspofungin is also metabolised in the liver and can cause hepatotoxic effects. Therefore we measured metabolic liver function capacity using LiMAx®and adapted the patient's dose of caspofungin to the evaluated liver function capacity to achieve an effective and liver-protective level of the active drug. After complicated medical history with 15 weeks of hospital stay, the patient was discharged in general good condition.
Conclusions:
To our knowledge, this is the first report that relates antimycotic drug dosing to a functional liver test. We provide a new approach for sepsis treatment considering liver function capacity to optimize dosage of hepatically metabolised drugs with potential hepatotoxic effects.
Insights
This case report introduces a novel approach to sepsis treatment by tailoring antifungal medication dosage to individual liver function. This method optimizes drug effectiveness while minimizing potential liver damage in critically ill patients.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Hepatology
Background:
- Sepsis, particularly fungal infections, poses a significant threat to patient survival.
- Impaired liver function in septic shock alters hepatic drug metabolism.
- Antifungal drug selection and dosing are critical challenges in sepsis management.
Observation:
- A 56-year-old male with invasive fungal infection and multiorgan failure presented with complications including renal infarction and ischemic colitis.
- The patient received systemic antifungal treatment with caspofungin, an echinocandin.
- Metabolic liver function was assessed using LiMAx® to guide caspofungin dosing.
Findings:
- Caspofungin dosing was adapted based on measured liver function capacity.
- This individualized approach aimed for effective and liver-protective drug levels.
- The patient was discharged in good condition after a prolonged hospital stay.
Implications:
- This is the first report linking antimycotic drug dosing to a functional liver test.
- A new strategy for sepsis treatment involves optimizing dosages of hepatically metabolized drugs based on liver function.
- This approach holds promise for improving outcomes in patients with impaired liver function and fungal sepsis.
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