Clinical Features Of Bacterascites And The Metagenomic Next-generation Sequence Application For Optimizing Diagnosis Of Ascites Infection In Cirrhotic Patients

Background:Ascites infections are frequent in patients with cirrhosis.According to current guidelines,two forms of ascites infections can be identified:spontaneous bacterial peritonitis(SBP)and bacterascites.SBP is the classical form of ascites infection.It has been investigated widely,in terms of treatment(antibiotics and albumin)and frequent clinical consequences.Few studies of bacterascites have been reported;therefore,knowledge of the clinical characteristics and management guidelines of bacterascites are limited.The positive rate of ascites culture is low.Currently,the empirical antibiotics treatment of ascites infection in cirrhotic patients based on the ascites neutrophil cell counts which were greater than 250/?l).The key step to prevent the complications of ascites infection is early diagnosis.Metagenomic next-generation sequencing(mNGS)for pan-pathogen(bacteria,virus,fungi)detection was identified as the next culture-independent game changer and the result is available within 48 hours.The clinical application of mNGS is mainly for unidentified central nervous system infection and pneumonia.So far,there is still a lack of relevant clinical studies on clinical application of mNGS method in optimizing the diagnosis of ascites infection in cirrhosis patients.Aim:(1)To assess the clinical features and outcomes of bacterascites in cirrhotic patients.(2)To evaluate the clinical application and clinical significance of mNGS method in the diagnosis of ascites infection in cirrhotic patientsMethod:(1)The first included 418 patients with ascites-positive cultures at 11 hospitals during 2012-2018.Clinical characteristics and outcomes were recorded.The second included 208 patients with sterile ascites from a prospective cohort(NCT02457637).Clinical features and outcomes of cirrhotic patients with or without bacterascites were investigated.(2)Cirrhotic patients with ascites were prospectively included from August 2019 to February 2020.The ascites and paired plasma samples were detected by mNGS.The clinical effect of the pathogen by mNGS detection was evaluated and the clinical characteristics and prognosis between mNGS-positive group and mNGS-negative group were further compared.Result:Bacterascites was diagnosed in 254/418(60.8%)patients,and culture-positive spontaneous bacterial peritonitis(SBP)in 164/418(39.2%)patients.Gram-positive bacteria were more prevalent in bacterascites patients than in culture-positive SBP patients(59.1%vs.22.0%;p<0.001).For patients with acute-on-chronic liver failure(ACLF,n=102)in bacterascites and culture-positive SBP groups,the 28-day transplant-free mortality(41.3%vs.65.5%;p=0.015)and the prevalence of in-hospital acute kidney injury(AKI)(84.8%vs 75%;p=0.224).For patients without ACLF in the bacterascites(n=208)and culture-positive SBP groups(n=108),the 28-day transplant-free mortalities were 13%vs.13.9%(p=0.822),the probabilities of progression to ACLF within 28 days were 10.1%vs 14.8%(p=0.216)and the prevalences of in-hospital AKI were 14.4%vs.30.6%(p=0.001).Bacterascites patients had higher 28-day mortality than those patients with sterile ascites,after propensity score matching(18.4%vs.8.6%;p=0.010)In this proof-of-concept study,84 cirrhotic patients with ascites were included prospectively.Of the 36 cirrhotic patients with ascites mNGS-positive,5 were culture-negative SBP,1 was culture-positive SBP,4 were bacterascites and 26 were sterile ascites.A total of 71 infections were identified in 36 patients and the percentages of Gram-positive bacteria,Gram-negative bacteria,virus,and fungi were 39.4%,33.8%,16.9%and 9.9%,respectively.The occurrences of fever and AKI in patients with ascites mNGS-positive were higher than those with ascites mNGS-negative(38.9%vs.10.4%,p=0.002;33.3%vs.14.6%,p=0.042).Of the 5 culture-negative SBP,the antimicrobial agents were adjusted according to ascites mNGS result in one case because of the empirical antibiotics treatment was ineffective.The remaining 4 cases were identified pathogens in ascites by mNGS detection.Of the 4 cases with bacterascites,2 were received early antibiotics treatment and 2 were identified rare infections by mNGS detection(vibrio cholerae and cryptococcus neoformans).Of the 26 cases with sterile ascites,3(11.5%)cases progressed to SBP within 30 days,1 case with gastrointestinal bleeding received antibiotics treatment according to ascites mNGS result and the ascites mNGS-positive result affected the management and treatment in 9(34.6%)cases.Conclusion:(1)Bacterascites patients had non-negligible poor clinical outcomes,including in-hospital AKI,progression to ACLF,and 28-day mortality.Future studies are warranted to expedite the diagnosis of bacterascites and optimize antibiotic treatment.(2)Ascites mNGS can improve the diagnosis of ascites infection in cirrhotic patients and help to provide the pathogen evidence,including bacteria,virus and fungi.The ascites mNGS had clinical effect in guiding the adjustment of antimicrobial agents,as well as early identifying rare infections.