| ObjectiveTo analyze the clinical characteristics,risk factors,treatment and outcome of patients with chronic and acute liver failure complicated with invasive pulmonary aspergillosis,so as to provide references and suggestions for early clinical detection and early treatment of such patients.MethodsIn this study,708 patients who were admitted to the Infection Department of Henan Provincial People’s Hospital and diagnosed with liver failure(according to the Guideline for Diagnosis and Treatment of Liver Failure(2018)standard)from January 2019 to December 2020 were retrospectively analyzed.According to the patients’ medical history,onset characteristics and progression speed of the disease,and according to the Guidelines for Diagnosis and Treatment of Liver Failure(2018),the patients were divided into three groups: acute/subacute liver failure,acute-on-chronic liver failure and chronic liver failure.The general clinical data of the patients were collected,and according to the diagnostic criteria for invasive aspergillosis agreed in EORTC/MSG,the patients with liver failure combined with invasive pulmonary aspergillosis were collected,and the incidence rate of IPA in patients with liver failure in each group was analyzed.Patients with acute on chronic liver failure were divided into IPA-combined group and IPA-free group according to whether IPA was combined.The data of gender,age,etiology,complications,use and time of antibacterial drugs and steroids,invasive examination or treatment,diabetes mellitus,and admission to ICU of the two groups were compared,and the independent risk factors of patients with IPA combined infection were analyzed.The clinical symptoms,imaging characteristics,laboratory test characteristics and fungal evidence,application of antifungal drugs and other data of patients with acute on chronic liver failure combined with IPA were collected,and the common clinical symptoms,imaging manifestations,laboratory data changes,fungal evidence of patients with acute on chronic liver failure combined with IPA were analyzed.According to the outcomes of patients with ALF combined with IPA,they were divided into an improvement group who gave up treatment or a death group.The sex and age of the patients,whether or not to receive antifungal treatment,drugs and time of antifungal treatment,combined complications,artificial liver treatment and neutropenia were compared,to explore the influencing factors of different outcomes of patients,and to analyze the incidence and mortality of ALF combined with invasive pulmonary aspergillosis,as well as the changes in previous reports,so as to provide reference and suggestions for the clinical treatment of patients with ALF combined with IPA.Statistical analysis was performed on the above data using SPSS21.0 software.Measurement data were expressed as mean standard deviation((?)s),and inter-group comparison was examined by independent sample t test or non-parametric test.Enumeration data were expressed as rates,and inter-group comparisons were performed using mx2 test or Fisher’s exact probability method.Multivariate Logistic regression was used to analyze the risk factors for acute on chronic liver failure complicated with IPA.P <0.05 indicated that the difference was statistically significant.Results1.A total of 708 patients with liver failure were included,including 94 patients with acute / subacute liver failure,490 patients with chronic and subacute liver failure and 124 patients with chronic liver failure.There were 525 males(74.2%)in patients with liver failure,with an average age of 51.94 years.Of the 708 patients with liver failure,410 patients were improved and discharged(57.9%),277 patients gave up treatment(39.1%),and 21 patients died in hospital(3.0%).After follow-up,patients who gave up treatment died one after another in a short period of time,and the total mortality rate of patients with liver failure was42.1%.Among the patients with acute / subacute liver failure,56 patients were improved and discharged(59.6%),32 patients gave up treatment(34.0%),6 patients died(6.4%),and the mortality rate was 40.4%.Among the patients with chronic and acute(subacute)liver failure,252 patients were improved and discharged(51.4%),223 patients gave up treatment(45.5%),15 patients died(3.1%),and the mortality rate was 48.6%.Among the patients with chronic liver failure,102 patients were improved and discharged(82.3%),22 patients gave up treatment(17.7%),and there were no hospital deaths.There were differences in mortality among acute / subacute liver failure,slow plus acute(subacute)liver failure and chronic liver failure,and the mortality of patients with slow plus acute(subacute)liver failure was the highest.Of all the 708 cases of liver failure,102 were suspected or clinically diagnosed as IPA,with an incidence of 14.4%.Eight patients with acute / subacute liver failure were complicated with IPA,with an incidence of 8.5%.Among the patients with chronic and acute liver failure,88 patients were complicated with IPA,with an incidence of 18.0%.Six patients with chronic liver failure were complicated with IPA,with an incidence of 4.8%.There was a statistical difference in the incidence among the three groups,and the incidence of IPA was the highest in chronic plus acute liver failure.2.Among the 490 patients with chronic plus acute liver failure,88 were suspected or clinically diagnosed as IPA,including 72 males and 16 females,with an average age of 51.18 years.Among them,39 were admitted to ICU treatment(44.3%),and the average stay in ICU treatment was 10.46 days.Among the patients with chronic and acute liver failure complicated with IPA,74 were complicated with ascites(84.0%),52 with hepatic encephalopathy(59.0%),42 with abdominal infection(47.7%),27 with hepatorenal syndrome(30.6%),18 with gastrointestinal bleeding(20.4%)and 1 with hepatopulmonary syndrome(1.1%).There were 16 patients with diabetes(18.1%).All patients were treated with antibiotics.Among them,32.9% of patients used less than 3 kinds of antibiotics,38.6% of patients used 4-5 kinds of antibiotics,28.4% of patients used more than 5 kinds of antibiotics,and the average time of using antibiotics was 24.97 days.Ten patients were treated with steroids(11.3%),of which 7 patients used steroids for more than 7 days(7.9%).80 patients received deep venous catheterization(90.9%),33 patients received thoracic,abdominal or biliary drainage(37.5%),and 76 patients received invasive procedures such as artificial liver(86.3%).The above data are analyzed by chi-square test or independent sample t-test.Patients with chronic and acute liver failure complicated with IPA and without IPA were admitted to ICU(0.013),days of ICU treatment(0.003),ascites(0.035),hepatic encephalopathy(0.005),hepatorenal syndrome(0.002),abdominal infection(0.018),use of antibiotics(0.000),treatment time of antibiotics(0.000),deep vein catheterization(0.002).There were significant differences between the two groups in drainage(Purge 0.012)and artificial liver therapy(Pure 0.003).Multivariate Logistic regression analysis showed that hepatorenal syndrome,abdominal infection and deep venous catheterization were independent risk factors associated with IPA.3.Of the 88 patients with chronic and acute liver failure complicated with IPA,40(45.45%)had no mycological evidence and were suspected to be IPA.The other 48 patients(54.55%)met both clinical features and mycological evidence and were clinically diagnosed as IPA.The shortest time from clinical symptoms to clinical diagnosis or suspected onset of IPA in patients with chronic and acute liver failure complicated with IPA is 1 week,the longest is 7.5 months,the median is 1 month,and the mode is 1 month.The most common clinical symptoms in patients with chronic and acute liver failure complicated with IPA were fever(62.5%),followed by cough,expectoration(50%),dyspnea(6.4%)and chest pain(3.8%).The main imaging findings were nodules(70.4%),followed by unilateral or bilateral lung field infiltration(29.5%),halo sign(28.4%)and cavity(20.7%).Among the 88 patients with chronic and acute liver failure complicated with IPA,46 patients had GM test greater than 1(52.2%),and 10 patients had Aspergillus flavus or Aspergillus fumigatus(11.3%)in coughed sputum.One week after the symptoms of liver failure,clinicians should be alert to the occurrence of IPA,and should be more vigilant in one month,monitor the patients’ symptoms,signs,GM test and improve the imaging examination.There were significant differences in WBC,N,N%,CRP,TBil and prealbumin between chronic and acute liver failure patients before and after IPA.It is suggested that WBC,N,N%,CRP,TBil increased and prealbumin decreased in patients with chronic and acute liver failure complicated with IPA.4.Of the 88 patients with chronic and acute liver failure complicated with IPA,26 were discharged with continuous antifungal therapy after improvement(29.6%),61 gave up treatment(69.3%),and 1 died(1.1%).Of the 88 IPA patients,86 received antifungal therapy(97.7%)after suspected diagnosis or clinical diagnosis.79 of the patients who received antifungal therapy were treated with voriconazole only(89.8%).Among the patients with chronic and acute liver failure complicated with IPA,26 patients improved,including 21 males and 5 females with an average age of 49.58 years,and 62 patients who gave up treatment or died,including 51 males and 11 females with an average age of 51.86 years.24 patients(92.3%)in the improvement group received antifungal therapy for more than one month.Among the patients in the abandoned treatment group,31(50.0%)received antifungal therapy for less than 7 days.There were significant differences between the two groups in the time of antifungal therapy(Pure 0.000),with other complications(0.011),before IPA(TBil 0.000),with IPA(PTA 0.002),TBil(0.000).The improved patients had fewer other complications before IPA,lower TBil,lower liver function deterioration and longer time of antifungal therapy after IPA.Patients who gave up or died before IPA had more complications,higher TBil,poorer basic liver function,significantly worse liver function after IPA,and shorter time of antifungal therapy.The changes of PTA and TBil were compared between the improved group and the abandoned treatment group at 1 week and 2 weeks after receiving antifungal therapy.In the improvement group,there was significant difference in TBil at 1 week and 2 weeks after treatment(P < 0.05).There was no significant difference in PTA and TBil between 1 week and 2 weeks in the abandoned group.One week after treatment,there was a significant difference in TBil between the improvement group and the abandonment group,and there were significant differences in PTA(0.017)and TBil(0.000)between the improvement group and the abandonment group 2 weeks after treatment.The basic condition of the liver of the improved patients was better,and the TBil decreased significantly after 1-2 weeks of antifungal treatment.The basic liver function of the patients who gave up or died was poor,and PTA and TBil did not improve significantly after 1-2 weeks of antifungal treatment.Conclusion1.Among the 708 patients with liver failure,patients with chronic and acute(subacute)liver failure accounted for the most,the mortality was the highest,and the incidence of IPA was the highest.The mortality of patients with chronic plus acute(subacute)liver failure complicated with IPA was significantly increased.2.Hepatorenal syndrome,abdominal infection and deep venous catheterization are independent risk factors associated with IPA.3.One week after the symptoms of liver failure,clinicians should be alert to the occurrence of IPA,be more careful in 1 month,timely monitor the patients’ symptoms,signs,laboratory examination,GM test,and carry out imaging examination if necessary.When patients with chronic and acute(subacute)liver failure develop symptoms such as fever,cough and hemoptysis.The GM test should be monitored when the symptoms of liver failure are aggravated,the infection index is significantly higher than before,and the liver function deteriorates obviously,and the imaging examination and sputum culture should be improved.When GM test is positive,imaging nodules with halo sign or cavity,or lung field infiltration and sputum culture positive,IPA should be highly suspected,diagnosed as soon as possible and antifungal treatment should be carried out immediately.4.When patients with chronic and acute liver failure complicated with IPA appear: poor basic liver function;many complications;liver function deteriorates significantly after IPA;liver function still does not improve significantly after 1-2 weeks of antifungal treatment,which may indicate a poor prognosis. |
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