Liver failure often complicated by fatal invasive aspergillosis
November 26 2013
Of nearly 800 patients with acute-on-chronic liver failure (ACLF), around 5% developed invasive pulmonary aspergillosis (IPA) with almost 95% of those patients going on to die despite antifungal treatment. Reporting from Zhejiang University, Hangzhou in China, Jiajia Chen and colleagues note that most deaths were due to progression of IPA, the remainder due to progression of liver failure. Only two patients survived with antifungal treatment. Survival was only achieved in patients who were able to take antifungal drugs for more than 5 days.
A patient with ACLF, showing hallmark signs of acute-on-chronic liver failure with fluid retention in the abdomen (ascites), in addition to jaundice. (Uni. San Diego, US)
90% of the patients who developed IPA were also prescribed corticosteroids, and these patients had worse survival (p = <0.01). Age and hepatic encephalopathy were also significant for increased mortality (p = 0.021 and p = 0.001). Until recently there was no analysis of the risk factors for IPA in patients with ACLF, with most prior emphasis being on transplantation and chemotherapy patients.
A diagnosis of probable IPA was made on the basis of the appearance of pulmonary consolidation or infiltrate on the thoracic image, and rapid progression with antibiotic-resistant fever as well as a positive sputum culture for Aspergillus spp. All the patients had a fever, in contrast to other risk groups in which fever is uncommon or late. The authors argue that patients with ACLF who have symptoms of antibiotic-resistant pneumonia should be started on antifungal treatment immediately. In addition, those being treated with voriconazole should be monitored carefully for toxic effects to the liver and kidneys.
A graph showing the survival time in ACLF with IPA versus ACLF without IPA. (Chen et al., 2013)
The precise cause of the immunodeficiency in hepatic failure is not well studied.
Diagnostic and therapeutic options for patients with IPA are poor, especially in liver failure as biopsy is not realistic and antifungal therapy is often hepatotoxic. The performance of diagnostic biomarkers in liver failure is barely studied. Additional pharmacodynamic study of antifungal drugs is required and rapid turnaround therapeutic monitoring is also likely to improve outcome. For better survival, there must be prompt clinical recognition, urgent diagnostic confirmation and immediate antifungal therapy is essential.