Abstract
BACKGROUND AND AIMS: Limited data exist on the role of systemic inflammation and gut barrier dysfunction in acute variceal bleed (AVB). We studied inflammatory markers and changes in the intestinal barrier in patients with AVB and assessed if these can be used to identify a higher risk subgroup with regard to outcomes. METHODS: In this prospective observational study, patients with cirrhosis and AVB presenting at a tertiary care center were stratified by whether or not they developed acute decompensation (AD) over 6 weeks follow-up. Utility of systemic inflammatory markers (interleukin-6 [IL-6], C-reactive protein), endotoxinemia (serum IgM/IgG anti-endotoxin antibodies), and duodenal epithelial tight junction proteins (TJPs) by immunohistochemistry (IHC) for tight-junction proteins (claudin-2,-4, zonula occludens-1(ZO-1), junctional adhesion molecule (JAM)) was assessed to predict the outcomes. These parameters were compared with a pre-existing cohort of patients with cirrhosis and no recent variceal bleed and with those without cirrhosis (dyspepsia with no endoscopic pathology). A nomogram was developed from multivariate model to predict 6-wk AD in patients with AVB. RESULTS: Patients with AVB(n = 66) (age:46.4 ± 11.7 years; etiology: alcohol/NASH/HBV/HCV [48.5%/12.1%/12.1%/7.6%]) were included. Twenty-four (36.3%) patients developed 6-wk AD. Patients with 6-wk AD had higher serum IL-6 (median: 156.14 pg/ml [IQR: 136.12-170.52] vs 58.28 pg/ml [31.70-110.67]; P < 0.001) and Child score (median: 9 [6.75-10.25] vs 7 [6-9]; P = 0.042) at baseline. Serum endotoxinemia and duodenal epithelial TJP were similar. A nomogram combining CTP and IL-6 was generated that predicted 6-wk AD with optimism-corrected c-statistic of 0.87. Comparison with non-bleeder cirrhosis (n = 52) (7.57 [5.48-9.87]) and dyspepsia controls (n = 53) (5.72 [4.40-6.45]; P < 0.001) also identified significant elevation of serum IL-6, not entirely explainable by derangements in TJP and bacterial translocation markers. CONCLUSION: 6-wk AD rates in patients with cirrhosis and AVB can be predicted using combination of Child score and serum IL-6.