A Cohort Study Of Posaconazole Prevent Invasive Pulmonary Aspergillosis Infection In Patients With Liver Failure

Objective: Liver failure is an advanced stage in the development of various chronic liver diseases with severe disease and high morbidity and mortality.These patients are immunocompromised,especially those with a history of glucocorticoids(GCs),and are susceptible to invasive pulmonary aspergillosis(IPA)infection,which greatly increases the difficulty of treatment and morbidity and mortality.Therefore,prevention of invasive aspergillosis is particularly important,and posaconazole has been recommended in several guidelines as the first choice for the prevention of fungal infections in hematological malignancies.This study will investigate the efficacy and safety of posaconazole in the prevention of invasive pulmonary Aspergillus infections in patients with liver failure treated with glucocorticoids,and provide ideas for better clinical management of these patients.Methods:This is an observational study,and patients with liver failure treated with glucocorticoids who were hospitalized in the Infection Department of the Third Hospital of Hebei Medical University from February 2015 to February 2022 were selected as study subjects.Patients who were in the early to middle stage of liver failure and treated with methylprednisolone sodium succinate according to the Guidelines for the Diagnosis and Treatment of Liver Failure(2018 edition)were included according to the inclusion criteria and divided into two groups according to the treatment regimen: 1.prophylaxis group with posaconazole suspension(200 mg/three times daily);2.prophylaxis group without posaconazole.Patients in both groups were matched two-by-two according to age,gender and baseline MELD score.Statistical analysis was performed using SPSS 26.0 software to compare the rate of invasive Aspergillus infection between the two groups.Independent risk factors affecting Aspergillus infection were screened by performing univariate analysis of possible risk factors for Aspergillus infection and logistic regression analysis of those that were statistically significant;survival statistics were analyzed using Kaplan-Meier survival curves,and survival comparisons between groups were made using P≤0.05 was considered to be a statistically significant difference.Results:A total of 108 patients were enrolled in this study,including 36 patients in the treatment group and 72 patients in the control group,based on two matching for age,gender and baseline MELD score.(1)There was no statistical difference between the two groups in terms of basic clinical information and risk factors affecting invasive Aspergillus infection(P > 0.05);(2)21 cases of invasive Aspergillus infection occurred during hospitalization,with an overall infection rate of 19.4%(1.8% in the treatment group and 17.6% in the control group),and the difference in the incidence of IPA between the two groups was statistically significant(x2 = 6.65,P = 0.01);(3)21cases of invasive pulmonary Aspergillus infection In the treatment group,there were 2 confirmed cases of IPA and 0 clinically diagnosed cases of IPA;in the control group,there were 5 confirmed cases of IPA and 14 clinically diagnosed cases of IPA,and the difference in the diagnostic classification of IPA between the two groups was statistically significant(x2=4.421,P=0.035);(4)The time of IPA in the two groups,the median time of infection in the treatment group was 18 days,and that in the control group was 18 days.(4)The median time to IPA in the two groups was 18 days in the treatment group and 11 days in the control group,and there was a statistically significant difference in the time to infection with invasive Aspergillus in the two groups(Z=-2.191,P=0.028);(5)The results of the logistic multifactor analysis suggested that CRP and glucocorticoid hormone application >7 days were independent risk factors for the complication of IPA in patients with liver failure treated with glucocorticoids;(6)There was a statistically significant difference between the two groups in terms of neutrophil(6)There was no statistical difference between the two groups in terms of adverse effects such as neutropenia,thrombocytopenia,gastrointestinal bleeding,nausea and vomiting,visual disturbance and discontinuation of medication(all P > 0.05);(7)Cumulatively,20 cases(18.51%)died and88 cases(81.48%)survived.Of the 21 patients with IPA,11(52.38%)died and 10(47.62%)survived;of the 87 patients without IPA,9(10.34%)died cumulatively and 78(89.66%)survived.The difference was statistically significant(x2=21.314,p<0.001).Conclusion:CRP and glucocorticoid administration >7 days were independent risk factors for the development of invasive pulmonary aspergillosis in patients with liver failure treated with glucocorticoids;posaconazole suspension 200mg(5ml)orally 3 times daily was effective in reducing the incidence of IPA infection in patients with liver failure treated with glucocorticoids,thereby improving survival without increasing adverse drug effects.