Preventive effects of antifungal drugs in patients with acute-on-chronic liver failure treated with glucocorticoid

Objective To explore the efficacy of glucocorticoid (GC) therapy on hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and the effectiveness and safety of voriconazole (VCZ) in preventing pulmonary Aspergillus infection in HBV-ACLF patients treated with GC. Methods Two hundred and thirty-two patients with HBV-ACLF were enrolled from January 2016 to December 2018 in the First Affiliated Hospital of Nanchang University. They were divided into non-GC group (104 cases), GC group (74 cases), and GC+ VCZ group (54 cases). The observation period was four months. The baseline liver function, the incidence of pulmonary Aspergillus infection, the survival rate during observation period, and the incidence of complications were compared among the three groups. The adverse reactions of VCZ were observed to identify the best dose for prevention. Quantitative data were analyzed by analysis of variance or rank sum test. Count data were analyzed by chi-square test or Fisher exact test. Results The baseline liver functions were not significantly different among the three groups (all P>0.05). The incidence of pulmonary Aspergillus infection in the GC group (22.97%(17/74)) was both higher than that in the non-GC group (5.77%(6/104)) and GC+ VCZ group (1.85%(1/54)), the differences were both statistically signifrcant (χ2=11.373 and 9.843, respectively, both P<0.01). The overall mortality rate of HBV-ACLF patients with pulmonary Aspergillus infection was 79.2%(19/24). The survival rate in non-GC group (37.5%(39/104)) showed no statistical difference with that in GC group (39.19%(29/74), χ2=0.052, P=0.819). The survival rate of GC+ VCZ group (66.67%(36/54)) was significantly higher than that in GC group and non-GC group (χ2 =12.126 and 9.431, respectively, both P<0.01). The blood concentrations of VCZ were randomly measured in 16 patients from the GC+ VCZ group, and the range was 0.82-5.38 mg/L, with no evident adverse reactions. Conclusions The GC treatment is effective in HBV-ACLF patients in early stage. The VCZ treatment effectively reduces the incidence of pulmonary Aspergillus infection in HBV-ACLF patients receiving GC treatment and increases the survival rate. Oral VCZ (200 mg/d) treatment has a stable blood concentration in HBV-ACLF patients, with rare adverse reactions and good safety. Key words: Hepatitis B virus; Glucocorticoid; Acute-on-chronic liver failure; Voriconazole