There was a wealth of excellent content related to Acute on Chronic Liver Failure (ACLF) at this year’s AASLD Liver Meeting, ranging from basic inquiry into mechanisms to clinical trials to large data analyses. 

There were interesting insights from the laboratory related to the pathogenesis of ACLF. Dr. Yasmina Chouik presented the association of circulating micro-RNA with infection and mortality in patients with ACLF.  This proved to be a valuable additional factor in predicting bacterial infection, nosocomial infections, and survival over 6 months, independent of MELD score. Dr. Ingrid Zhang described the unique nature of mitochondrial and leukocyte dysfunction, suggesting a particular relevance distinguishing ACLF.

Specific measures which may aid in the long-term prevention of ACLF remain uncertain.  A group from the University of Pennsylvania led by Drs. Nadim Mahmud and David Kaplan presented analysis of a large cohort suggesting that patients on statins were less likely to develop ACLF.  Extensive analytical measures were used to adjust for propensity to receive statin therapy and there did appear to be association with dose and duration of therapy, potentially related to reduced liver inflammation, anti-fibrinolytic properties, or reduced hepatic endothelial dysfunction; however caution is still required in interpretation of these retrospective data.

Active treatments remain an area of keen interest, with new data presented showing antibiotic prophylaxis with norfloxacin may reduce the incidence of bacterial infection (18% vs 32% with placebo) over 1 month among hospitalized patients with ACLF.  This was predominantly reduction in urinary tract infection and spontaneous bacterial peritonitis. This resulted in numerically greater 1-month survival, as well as lower risk of hepatic encephalopathy; however these differences did not reach statistical significance in this study, presented by Dr. Anand Kulkarni.

Fungal infections remain a common, morbid, and underappreciated complication of patients with ACLF.  An open-label RCT showed that patients admitted to the ICU with ACLF with early treatment prior to a definitive diagnosis of fungal infection had lower mortality, with a number needed to treat of only 3 to prevent 1 death.  Extrapolation is challenging from this relatively small cohort with somewhat heterogeneous indications for treatment, but it is an interesting result that merits further attention and underscores the opportunity for better supportive management of patients with ACLF. This study was presented by Dr. Arun Valsan.

Management of ACLF in the ICU is a topic of high clinical interest, reflected by discussion in the joint ACLF and Pediatric Liver Disorders Special Interest Group presentation on ICU care of ACLF and "Too Sick for Transplant?"  There were also updates on outcomes of ACLF ICU admissions from a multicenter European group presented by Dr. Thierry Artzner. He showed that outcomes with transplant for grade 3 ACLF in the ICU were not associated with overall center transplant volume, but specifically with volume of patients listed and transplanted with ACLF Grade III. In a second presentation, he showed that within-center posttransplant outcomes improved for these patients over time. Together, these suggest the value of a center’s experience in management and selection of liver transplant candidates among a very sick population (ACLF-3).

Interest in and exposure of ACLF as an area of study will continue to grow and I anticipate more exciting discussion at next year's meeting and look forward to actionable findings in the near future to help identify, protect, and treat patients with this highly morbid condition.