Study On The Side Effects Prevention And Safety Of Voriconazole In Glucocorticoid Application Of HBV-Related Acute-on-Chronic Liver Failure

Objective:To explore the efficacy and safety of voriconazole in the prevention of pulmonary aspergillosis infection in HBV-related ACLFglucocorticoid applications.Method:Retrospective analysis of patients with HBV-related ACLF who were hospitalized in the Department of Infectious Diseases,the First Affiliated Hospital of Nanchang University from January 2016 to December 2018.According to different treatment options,they were divided into three groups: unused glucocorticoid group:104 cases;used glucocorticoid group : 74 cases;group of glucocorticoid combined with voriconazole tablets(200mg / d): 54 cases;three groups of baseline data for statistical pairing analysis no difference.The survival rate of three groups of patients,the incidence of pulmonary aspergillosis infection,the incidence of complications were compared,and the adverse reactions of voriconazole tablets and the blood concentration of voriconazole in some patients were observed to explore the optimal dose of voriconazole.Results:1.The survival rate of the glucocorticoid combined with voriconazole tablet group was significantly higher than that of the unused glucocorticoid group(36/54 vs39/104)(P<0.01).The survival rate of the glucocorticoid combined with voriconazole tablet group was also higher than that of the used glucocorticoid group(36/ 54 vs29/74)(P = 0.002);the survival rate of the used glucocorticoid group was slightly higher than that of the unused glucocorticoid group,but there was no statistical difference(29/74 vs 39/104)(P = 0.819).2.the incidence of pulmonary Aspergillus infection in the glucocorticoid group was significantly higher than that in the unused glucocorticoid group(17/74 vs 6/104)(P=0.001);the incidence of pulmonary Aspergillus infection in the glucocorticoid group was also significantly higher than that in the glucocorticoid combined withvoriconazole tablet group(17/74 vs 1/54)(P=0.002);the incidence of pulmonary Aspergillus infection in the glucocorticoid combined with voriconazole tablet group was lower than that in the unused glucocorticoid group(1/54 vs 6/104)(P=0.467),but no statistical difference.3.Comparison of the incidence of complications in three groups:(1)spontaneous bacterial peritonitis: glucocorticoid combined with voriconazole tablet group(24/54)< used glucocorticoid group(35/74)< unused glucocorticoid group(65/104);(2)hepatic encephalopathy: glucocorticoid combined with voriconazole tablet group(16/54)< unused glucocorticoid group(35/104)< used glucocorticoid group(36/74);(3)hepatorenal syndrome: glucocorticoid combined with voriconazole tablet group(3/54)< unused glucocorticoid group(14/104)< used glucocorticoid group(11/74);(4)upper gastrointestinal bleeding: glucocorticoid combined with voriconazole tablet group(1/54)<used glucocorticoid group(3/74)< unused glucocorticoid group(13/104).4.The blood concentration of voriconazole in some patients with randomized glucocorticoid combined with voriconazole tablet group fluctuated at 0.82-5.38 mg/L(reference value 1-5.5 mg/L).All patients who received oral voriconazole tablets(200mg/d)showed no obvious adverse reactions.Conclusion:Oral administration of voriconazole tablets 200mg/qd can effectively prevent the probability of glucocorticoid treatment of HBV-associated ACLF patients with pulmonary Aspergillus infection,thereby improving the survival rate,without increasing complications,and the blood concentration is stable,and adverse reactions are rare.