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New protocol for treating invasive aspergillosis with voriconazole in liver failure patients

March 09 2018

Acute-on-chronic liver failure (ACLF) is a life-threatening condition that occurs when a patient with chronic liver disease decompensates, and is associated with multi-organ failure and high mortality. Among patients with ACLF, the prevalence of invasive pulmonary aspergillosis (IPA) is estimated to be 5–14%, with a short-term mortality of 73–100%. Treatment of this with the first-line antifungal voriconazole is unfortunately limited by its hepatotoxic properties.

Dr Jie Gao and colleagues recently published a study of patients at the Hepatology Unit of Nanfang Hospital (China). Of 101 patients who had been diagnosed with both ACLF and a lung infection, 39% were found to have probable or possible IPA. Mean time from ACLF diagnosis to development of probable IPA was 13 days, and three of those patients also had a concomitant bacterial lung infection.

The group used therapeutic drug monitoring to develop a treatment protocol for voriconazole, based on Chinese ACLF patients with moderate body weight (range 62–71 kg) and a CYP2C19 polymorphism for slow voriconazole metabolism. Oral voriconazole was given every 12 hours, with a loading dose (0.2g) and a maintenance dose (0.1g) optimised to produce trough concentrations of 1–5 μg/ml (for comparison the standard regimen is 0.4g and 0.2g respectively).

Take-home messages for clinicians:

  • IPA in an ACLF patient may manifest as a rise in temperature alongside a worsening of their overall condition – CRP, leukocyte count and procalcitonin may not change.
  • Patients receiving high doses of corticosteroids are at greater risk of IPA, and patients with a CLIF-SOFA lung score of 2 had a worse prognosis.
  • The suggested dosage of oral voriconazole is lower than that for patients with no liver disease or with Child-Pugh A/B liver cirrhosis, due to drug interactions with the cytochrome P450 system enzymes. Oral voriconazole should be given every 12 hours, with a loading dose of 0.2g and a maintenance dose of 0.1g.

Read the full paper: Gao et al (2018) Improving survival of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis. Br J Clin Pharmacol.