Plasma exchange does not improve overall survival in patients with acute liver failure in a real-world cohort.

Background & Aims: Therapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF.

Non-selective beta-blocker is associated with reduced mortality in critically ill patients with cirrhosis: A real-world study.

Background: Apart from direct portal pressure reduction, non-selective beta-blockers (NSBB) modulate inflammatory response, which could be beneficial in patients with acute decompensation (AD). We therefore aimed to evaluate the effect of NSBB on 28-day mortality and markers of systemic inflammation in a propensity score-matched (PSM) cohort of AD patients requiring intensive care unit (ICU) admission.

Methods: Patients were recruited from registry of AD patients requiring ICU admission.

Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor.

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO/FiO (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns.

Location and allocation: Inequity of access to liver transplantation for patients with severe acute-on-chronic liver failure in Europe.

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers.

Overt hepatic encephalopathy is an independent risk factor for de novo infection in cirrhotic patients with acute decompensation.

Background: The occurrence of overt hepatic encephalopathy (OHE) is associated with increased mortality. HE is commonly precipitated by infection, but whether HE predisposes to new infection is unclear. This study aimed to test if OHE predisposes to de novo infection during hospitalisation and its association with short-term mortality.

Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF.

Background And Aims: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.

Material And Methods: Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.

Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding.

Background & Aims: Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic shunt (TIPS) improves survival in patients with failure to control OGVB and ACLF.

Methods: Data on 174 consecutive eligible patients, with failure to control OGVB between 2005 and 2015, were collected from a prospectively maintained intensive care unit registry.

An Accurate Data Preparation Approach for the Prediction of Mortality in ACLF Patients using the CANONIC Dataset.

The incidence of chronic liver disease has increased in Europe and can lead to Acute on Chronic Liver Failure (ACLF) which is associated with high levels of mortality due to multisystem organ failure. The characteristics of the ACLF patients can change very rapidly within a short period of time. Continuous assessment of their recovery status is critical for clinicians to adjust and deliver effective treatment.

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single-Center, Clinical Experience in 105 Patients.

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large-volume transfusion. This retrospective, single-center study reviewed clinical use of PCC in patients with acute/chronic liver disease.

Prognostic Role of Ammonia in Patients With Cirrhosis.

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in patients with cirrhosis and acute decompensation is unknown. The aims of this study were to determine the relationship between ammonia levels and severity of HE and its association with organ dysfunction and short-term mortality. We identified 498 patients from two institutions as part of prospective observational studies in patients with cirrhosis.

Neurological Monitoring in Acute Liver Failure.

Cerebral oedema and Intracranial Hypertension (ICH) are serious complications of acute liver failure affecting approximately 30% of patients, resulting in neurological injury or death. Multiple pathogenetic mechanisms contribute to the pathogenesis of HE including circulating neurotoxins such as ammonia, systemic and neuro-inflammation, infection and cerebral hyperaemia due to loss of cerebral vascular autoregulation. Early recognition and diagnosis is often difficult as clinical signs of elevated Intracranial Pressure (ICP) are not uniformly present and maybe masked by other organ support.

Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure.

Background: Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis and is defined by organ failure and high rates of short-term mortality. Patients with ACLF are managed with multiorgan support in the intensive care unit (ICU). Currently, it is unclear when this supportive care becomes futile, particularly in patients who are not candidates for liver transplant.

Long-term outcome in patients with acute liver failure.

Background & Aims: Acute liver failure patients who meet poor prognostic criteria have high early mortality without emergency liver transplantation. A recent study however, reported that patients that survive spontaneously have a poorer outcome compared with patients undergoing transplantation. In this single centre study, we aimed to confirm or refute this observation.

A case study of likely wild-type cardiac transthyretin amyloidosis causing rapid deterioration.

We present the case of an 88-year-old gentleman who presented to hospital septic with bilateral leg cellulitis, pulmonary oedema and hypotension. He had no history of heart disease but had had bilateral carpal tunnel releases. His condition deteriorated with refractory hypotension in spite of fluid filling, inotropic and vasopressor support.