The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early.

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Hepatic encephalopathy (HE) is a common feature of acute-on-chronic liver failure (ACLF). Although ammonia, inflammation, and cerebral oxygenation are associated with HE in acute liver failure, their roles in ACLF are unknown. The aim of this prospective, longitudinal study was to determine the role of these pathophysiological variables in ACLF patients with and without HE. We studied 101 patients with ACLF admitted to the intensive care unit. Severity of ACLF and HE, arterial ammonia, jugular venous oxygen saturation (JVO 2 ), white blood cell count (WCC), and Creactive protein were measured at days 0, 1, 3, and 7. Patients were followed until death or hospital discharge. Mortality was high (51 patients, 50.5%), especially in patients with HE of whom 35 of 53 (66.0%) died regardless of ACLF severity. At baseline, increased WCC and abnormal JVO 2 (high or low) were independent predictors of death. Further deterioration in inflammation, JVO 2 , and ammonia were also predictive of mortality. JVO 2 deviation and hyperammonemia were associated with the presence and severity of HE; improvement in these parameters was associated with a reduction in HE grade. No direct interaction was observed between these variables in regards to mortality or HE. In conclusion, this study describes potential mechanisms of HE in ACLF indicating that ammonia and abnormal cerebral oxygenation are important. The results suggest that ammonia, JVO 2 , and WCC are important prognostic biomarkers and therapeutic targets. The relative roles of these pathophysiological factors in the pathogenesis of HE in ACLF or guiding therapy to improve survival requires future study. Liver Transplantation 22 732-742 2016 AASLD.Received November 21, 2015; accepted February 20, 2016. Acute-on-chronic liver failure (ACLF) is characterized by acute deterioration of cirrhosis resulting in organ failures in association with systemic inflammation and high mortality.(1-3) Hepatic encephalopathy (HE) in patients with cirrhosis often requires hospitalization, particularly the clinically manifest or "overt" form.(4) In hospitalized patients with cirrhosis with HE, Cordoba et al. (4) showed the presence of ACLF defined their in-hospital and 1-year mortality and that HE in ACLF was associated with a marked systemic inflammatory response. Because ACLF itself is associated with high mortality rates, systemic inflammation, and organ failures, it is not clear which pathophysiological factors associated with HE are relevant to patients with ACLF and superimposed HE.Data from experimental models of ACLF suggest hyperammonemia, inflammation, astrocyte swelling, altered cerebral blood flow (CBF), and cerebral edema are potential contributory mechanisms for HE development. (5,6)