Su1515 Role of Probiotics in Hepatic Encephalopathy: An Updated Meta-Analysis of Randomized Trials

Hepatic encephalopathy (HE) is a component of acute-on-chronic liver failure (ACLF).However its competing impact with ACLF on in-hospital mortality is unclear.Aim: 1. Define the contribution of HE with/without ACLF on in-hospital mortality in NACSELD (North American Consortium for Study of End-stage Liver Disease) 2. Define regional variations in HE outcomes.Methods: Cirrhotic inpatients were enrolled and followed till discharge/inhospital death.Pts were divided by West-Haven criteria (0, 1-2 and 3-4) for HE severity during admission.ACLF was defined as ‡2 of: 3-4 HE, ventilation, dialysis or shock.Survival was compared between the five gps (no HE/no ACLF, 1-2 HE/no ACLF, 1-2 HE/ACLF and 3-4 HE/no ACLF, 3-4HE/ACLF) & by region using unadjusted/adjusted (for demographics, co-morbidities, MELD, non-HE organ failures) regression models.NACSELD regions are Gp 1(NE US), Gp 2 (SE US), Gp 3 (SW US) &Gp 4 (Canada).Results: 1522 pts (age 57, MELD 17, 45% alcoholic, 57% prior HE, 38% on rifaximin, 40% infections) were included.During the hospitalization, 517 had HE (372 1-2, 145 grade 3-4) &104 developed ACLF (Table ).HE survival: Grade 3-4 vs. Grade 1-2 & no-HE pts had higher MELD (22 vs 18/ 18, p<0.0001),ACLF (46% vs. 10/4% p<0.001), diabetes (43% vs 40%/33%, p=0.03) and in-hospital mortality (27% vs. 5%/4%,p<0.0001).In-hospital mortality with grade 3-4 HE was significant(OR 3.3,p<0.0001)independent of MELD, WBC and non-HE organ failures.HE/ACLF interaction: Both HE+ACLF gps had higher admission MELD/WBC , greater % SIRS/infections, & the highest unadjusted in-hospital mortality (Table ).The HE gps regardless of ACLF were similar on cirrhosis details.Unadjusted ORs for in-hospital mortality was higher for ACLF+HE groups vs. no-ACLF/HE gps (3-4HE/ACLF vs 3-4HE/noACLF OR 11.3, 1-2HE/ACLF vs 1-2HE/noACLF OR 10.3, all p<0.001) & in those with higher HE grade+ACLF (3-4HE/ACLF vs 1-2HE/ACLF OR 3.3 p=0.01, 3-4HE/noACLF vs 1-2HE/no-ACLF OR 3.0 p=0.04).However, when adjusted for individual organ failures, age, WBC, infections & SIRS on regression, only HE grade remained significant (grade 3-4 HE/ACLFvs 1-2HE/ACLF OR 4.0 p=0.04).Regional comparison: 533 were in Gp 1, 374 in gp 2, 375 in gp 3 and 281 pts in gp 4. Demographics, MELD score, %SIRS/prior HE, & infections/ ACLF were similar between regions.Rifaximin use was lowest (6% gp 4 vs. 50%, 39% & 44% in gps 1-3, p<0.0001), while admission creatinine (2.3 vs. 1.4,1.3,1.5 p=0.003) & in-hospital mortality were highest (10% gp 4 vs. 6%, 5%,5% in gps 1-3, p=0.05) in Gp4.The high gp 4 mortality was significant on regression (adjusted OR gp 4 compared to gp 1:5.6, vs gp 2 OR:6.3, vs gp 3:7.1, p<0.0001).Conclusions: HE is a significant determinant of in-hospital mortality with or without the presence of ACLF.There is considerable regional variation within North America with HE-related in-hospital mortality.