*Purpose: One of the most common precipitants of acute on chronic liver failure (ACLF) in cirrhotic patients is sepsis. We aimed to evaluate the relationship between infection and the development of organ failure/important clinical outcomes in ACLF patients admitted to ICU.

*Methods: Retrospective cohort analysis of all cirrhotic patients admitted to intensive care units (ICU) at Northwestern Memorial Hospital between 1/2010-12/2017. All patients required ICU admission for a least 48 hours. Primary outcome was overall survival and secondary outcomes included transplant-free survival and receipt of liver transplant (LT).

*Results: Of 703 patients admitted to ICU (62% (n=433) male), 506 (72%) were alive at hospital discharge with 15% (n=104) receiving LT. The most common etiology of cirrhosis was alcohol (n=238, 34%). During ICU stay, vasopressors were used in 41%, renal replacement therapy (RRT) in 34%, and mechanical ventilation (MV) in 71% of patients. On Day 1 of ICU admission, 99 (14%) had ACLF Grade 1, 157 (23%) had ACLF-2, and 271 (39%) had ACLF-3. Mean CLIF_ACLF score was 56 (11) on ICU Day 1, 53(11) on Day 3 and 55 (10) on Day 7. Overall 198 (28%) patients were colonized with VRE, 35 (5%) with MRSA and 24 (3%) with ESBL. Most common infections were bacterial pneumonia (n=241, 34%) and bacteremia (n=201,29%). Compared with ACLF patients who survived to hospital discharge (n=506), non-survivors (n=197) were more likely to require vasopressors (61% vs. 32%), RRT (53% vs. 26%), and MV (91% vs. 63%; p<0.001 for all). ACLF non-survivors had higher CLIF_C ACLF scores on ICU Day 1 (61 vs. 54), Day 3 (60 vs. 50) and Day 7 (59 vs. 53; p<0.001 for all). ACLF non-survivors were more likely to have septic shock (56% vs. 23%), bacterial pneumonia (44% vs. 30%) and bacteremia (38% vs. 25%; p<0.002 for all). Rates of colonization for VRE (32% vs. 27%), MRSA (3% vs.6%), or ESBL (3% vs. 4%) were similar between non-survivors and survivors (p>0.2 for all). Patients with ACLF Grade 3 (n=271) were more likely to have bacterial pneumonia (54% vs. 22%) and bacteremia (40% vs. 21%; p<0.001 for both) than those with lower ACLF Grades (n=426). Despite this, ACLF Grade 3 patients were more likely to receive LT (n=69, 26%) than patients with lower ACLF Grades (n=35, 8%, p<0.001).

*Conclusions: Sepsis/bacteremia is associated with worse outcomes in ACLF patients. Increased organ failures/higher burden of illness did not preclude ACLF patients from receiving LT in this cohort.

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