Methods
The electronic health records of all children with liver disease and high SAAG ascites who had been subjected to abdominal paracentesis from January 2007 to January 2012 were analyzed.
Patients were classified on the basis of the ascitic fluid examination as ascitic fluid infection present (AFI) or not present (No-AFI). AFI was classified as spontaneous bacterial peritonitis (SBP, neutrophils ≥250 cells/mm3 and positive ascitic fluid bacterial culture), culture negative neutrocytic ascites (CNNA, neutrophil count ≥250 cells/ mm3 and negative ascitic fluid culture) and monomicrobial non-neutrocytic bacterascites (MNBA, neutrophils <250 cells/ mm3 and positive ascitic fluid culture) (2).
All children with new onset ascites, patients with ascites who were admitted to the hospital and those who developed signs/symptoms of AFI were subjected to diagnostic paracentesis with full aseptic precautions (3). Bedside inoculation of ascitic fluid in aerobic and anaerobic blood culture bottles was done.
The nature of liver disease was classified as AVH, ALF, CLD or EHPVO as per standard criteria. CLD was diagnosed by clinical, biochemical, ultrasonographic (nodular liver with portosystemic collaterals) and endoscopic (presence of ≥ grade II esophageal varices) findings with or without liver histology. Etiology of CLD was determined as per standard criteria (17), and those with no known etiology were labeled as cryptogenic. AVH was diagnosed on the basis of clinical symptoms, raised transaminases and positive viral serology for hepatitis A virus (IgM anti-HAV), hepatitis E (IgM anti-HEV) or hepatitis B virus (HBsAg and IgM anti-HBc) and complete recovery on follow-up. ALF and EHPVO were defined as per the Pediatric Acute Liver Failure Study Group and Asia Pacific Association for Study of Liver criteria respectively (18, 19).
The clinical manifestations, including features of AFI and presence of complications such as hepatic encephalopathy (HE), gastrointestinal bleeding (GIB), and acute kidney injury (AKI), were recorded. Presence of infection at other sites like pneumonia (clinical features and chest imaging), urinary tract infection (UTI: presence of pyuria and ≥ 100,000 colonies per mL of a single uropathogenic organism) or bacteremia (positive blood culture) was noted. Severity of HE was graded as per standard definition (20). AKI was diagnosed in the presence of decreased urine output (<1mL/kg/hr) and elevated serum creatinine above the age-specific normal range.
The liver function tests including international normalized ratio [INR] and creatinine were recorded. Child-Pugh (CP), Pediatric end-stage liver disease (PELD, age <12 years) and Model for End-Stage Liver Disease (MELD, ≥12years old) scores were calculated for CLD patients (21).
Patients with an ascitic fluid neutrophil count of ≥250 cells/mm3 with or without positive culture were given intravenous cefotaxime (100 mg/kg/day, BD doses, 5 days) which was modified later as per culture sensitivity and clinical response (3). As patients with CNNA and SBP are treated similarly, they have been clubbed together for analysis (3). Standard medical therapy was given as per the clinical status of the patient and etiology of liver disease. CLD patients admitted with gastrointestinal bleeding were given antibiotics for 7 days as per standard recommendation (3). Norfloxacin prophylaxis (5mg/kg/day) was given to SBP/ CNNA patients at discharge until resolution of ascites (3). Patient outcome after discharge, duration of follow- up and recurrence of ascitic fluid infection was noted.
The study was approved by the Institutional Ethics Committee, SGPGIMS and conforms to the ethical guidelines of the 1975 Helsinki Declaration.
Statistical Analysis
SPSS version 17.0 was used for analysis (SPSS, Chicago, IL). Mann-Whitney U test was used for continuous variables and Chi square/Fisher exact test was used for categorical variables.
Univariate analysis was done to identify factors predicting poor outcome in CLD children with AFI and those with a p value of <0.1 were then subjected to multivariate analysis by the stepwise forward regression method. Survival rates were compared using Kaplan-Meier method with log rank (Mantel-Cox) comparison of cumulative survival. A p value of <0.05 was considered significant.