• acute‐on‐chronic liver failure
• liver support systems
• liver transplantation

• Humans
• Acute-On-Chronic Liver Failure/therapy
• Acute-On-Chronic Liver Failure/surgery
• Liver Transplantation
• Liver, Artificial

• Cirrhosis
• Hepatopulmonary syndrome
• Hepatorenal syndrome
• Transjugular intrahepatic portosystemic shunt

• Multiple organ dysfunction syndrome (MODS)
• Organ crosstalk
• Organ failure
• Sepsis

• Humans
• Plasma Exchange
• Renal Dialysis
• Albumins/therapeutic use
• Acute-On-Chronic Liver Failure/therapy
• Liver Failure, Acute/therapy
• Liver Failure/therapy
• Treatment Outcome

• immunomodulation
• liver failure
• leukocytes
• cytokines

• Humans
• Acute-On-Chronic Liver Failure/therapy
• End Stage Liver Disease/complications
• End Stage Liver Disease/therapy
• Immunomodulation
• Multiple Organ Failure/etiology
• Multiple Organ Failure/therapy
• Prognosis

• P30 DK081943 NIDDK NIH HHS
• UM1 TR004404 NCATS NIH HHS

• Acute-on-chronic liver failure
• Artificial liver support system
• Hepatitis B
• Immunophenotype
• Mass cytometry

• Humans
• Acute-On-Chronic Liver Failure/therapy
• Acute-On-Chronic Liver Failure/complications
• Hepatitis B virus
• CD8-Positive T-Lymphocytes
• Liver, Artificial/adverse effects
• Hepatitis B
• Prognosis
• Hepatitis B, Chronic/therapy

• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• 2018ZX10101-001 National Science and Technology Major Project
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation
• LQ17H030002 Youth Fund Project of Zhejiang Provincial Natural Science Foundation

• NETs
• ROS
• chemotaxis
• cirrhosis
• neutrophils
• phagocytosis

• acute kidney injury
• bile cast nephropathy
• case report
• extracorporeal liver support
• molecular adsorbent recirculating system

• Acute kidney injury
• Biomarkers
• Hepatorenal syndrome
• Liver cirrhosis
• Terlipressin

• Humans
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/therapy
• Hepatorenal Syndrome/etiology
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/drug therapy
• Liver Transplantation
• Vasoconstrictor Agents/therapeutic use
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/etiology
• Acute Kidney Injury/therapy

• Acute liver failure (ALF)
• acute-on-chronic liver failure (ACLF)
• albumin dialysis
• apheresis and detoxification techniques
• extracorporeal liver support
• renal-replacement therapy

• Humans
• Ammonia
• Critical Illness
• Prospective Studies
• Retrospective Studies
• Renal Dialysis
• Liver Failure
• Albumins
• Bilirubin

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20^th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

• Liver failure
• Transplantation
• Blood purification
• Liver replacement therapy
• Artificial extracorporeal systems
• Transplant-free survival

• Acute liver failure
• Acute on chronic liver failure
• Albumin dialysis
• Artificial liver support
• Molecular Adsorbent Recirculating System™
• Plasma exchange

• acute kidney injury
• albumin dialysis
• extracorporeal membrane oxygenation
• extracorporeal organ support
• hemodialysis
• hemofiltration

• Cardiovascular; EXTRIP; hemodialysis; hemoperfusion; calcium channel blocker; overdose

• BioLogic-DT
• ELAD
• Liver support therapy
• MARS
• Network meta-analysis
• Overall survival
• Plasma exchange
• Prometheus
• SUCRA
• Transplant-free survival

• Albumin dialysis
• CytoSorb®
• Extracorporeal liver support
• Hemoperfusion
• MARS®

• Acute liver failure
• Albumin dialysis
• Artificial liver support
• Liver failure
• MARS
• Molecular adsorbent recirculating system

Since December 2019, the novel coronavirus (SARS-CoV-2) emerged in Wuhan and rapidly spread throughout the world. There are nearly 3 951 905 confirmed cases of novel coronary pneumonia and more than 275 067 deaths worldwide, [JHU data-09/05/2020, https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6]. A great number of patients contracted SARS-Cov-2 pneumonia (COVID-19). SARS-CoV-2 invades human target cells through receptor angiotensin-converting enzyme II (ACE2), which are expressed in the lung, kidney, and ileum and mediate inflammatory responses and immune activities. High plasma levels of proinflammatory cytokines were detected in the infected patients. These factors may predispose transplant patients to high risk of poor outcomes. Therefore, transplant patients might be affected by this coronavirus infection and protection of allografts should receive special attention during this outbreak. In the present study we attempt to delineate the transplant-related biology of SARS-CoV-2 infection.

Liver surgery is one of the most complex surgical interventions with high risk and potential for complications. Posthepatectomy liver failure (PHLF) is a serious complication of liver surgery that occurs in about 10% of patients undergoing major liver surgery. It is the main source of morbidity and mortality. Appropriate surgical techniques and intensive care management are important in preventing PHLF. Early start of the liver support systems is very important for the PHLF patient to recover, survive, or be ready for a liver transplant. Nonbiological and biological liver support systems should be used in PHLF to prepare for treatment or organ transplantation. The definition of the state, underlying pathophysiology and treatment strategies will be reviewed here.

• Liver surgery
• Posthepatectomy Liver Failure
• Prevention
• Treatment

Calcium channel blockers are highly protein-bound medications frequently used in the management of hypertension. Overdose results in severe hypotension and is the fourth most common cause of toxicity-related deaths in the United States. Management is mostly supportive, with currently no standard role for targeted drug removal. The protein-bound nature of these medications presents the option of utilizing albumin dialysis for their removal and for the reversal of associated shock.

We present two cases of life-threatening intentional amlodipine overdoses successfully treated with albumin dialysis. Both patients experienced profound distributive shock in the setting of preserved cardiac contractility that was refractory to maximal vasoactive agent support.

After initiation of albumin dialysis, the patients showed rapid hemodynamic improvement and were able to be weaned off vasopressor support.

These cases demonstrate the safety and efficacy of albumin dialysis in the management of near-fatal calcium channel blocker overdoses related to amlodipine and offer an additional therapeutic option apart from conventional supportive care. Importantly, these cases were not associated with impaired cardiac contractility, thereby making venoarterial extracorporeal membrane oxygenation a less preferable option. Furthermore, this therapeutic benefit of albumin dialysis can potentially be extended to the management of toxicity related to other highly protein-bound drugs and toxins.

• albumin dialysis
• amlodipine
• calcium channel blocker
• continuous renal replacement therapy
• toxicology
• vasoplegia

• Acute-on-chronic liver failure
• Immunotherapy
• Pathogenesis
• Predictors

• Acute-On-Chronic Liver Failure/immunology
• Acute-On-Chronic Liver Failure/therapy
• Albumins/therapeutic use
• Cytokines/blood
• Disease Susceptibility/immunology
• Glucocorticoids/therapeutic use
• Granulocyte Colony-Stimulating Factor/therapeutic use
• Humans
• Immunotherapy
• Infections/immunology
• Inflammation/blood
• Inflammation/etiology
• Liver, Artificial
• Monocytes

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

• Acute kidney injury
• Acute-on-chronic liver failure
• Chronic liver disease
• Hepatorenal syndrome
• Plasma perfusion and bilirubin adsorption and double plasma molecular absorption system
• Fractionated plasma separation and adsorption
• Molecular adsorbent recycling system
• Single-pass albumin dialysis

• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/etiology
• Acute Kidney Injury/therapy
• Acute-On-Chronic Liver Failure/complications
• Acute-On-Chronic Liver Failure/immunology
• Acute-On-Chronic Liver Failure/pathology
• Creatinine/blood
• Extracorporeal Circulation/instrumentation
• Extracorporeal Circulation/methods
• Granulocyte Colony-Stimulating Factor/therapeutic use
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/etiology
• Hepatorenal Syndrome/therapy
• Humans
• Kidney/blood supply
• Kidney/immunology
• Kidney/pathology
• Liver/immunology
• Liver/pathology
• Liver Cirrhosis/complications
• Liver Cirrhosis/immunology
• Liver Cirrhosis/pathology
• Liver Transplantation
• Liver, Artificial
• Prognosis
• Severity of Illness Index
• Treatment Outcome
• Vasoconstrictor Agents/therapeutic use

Cirrhosis is a leading cause of morbidity and mortality throughout the world. Significant complications include variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, and infection. When these complications are severe, admission to the intensive care unit (ICU) is often required for organ support and management. Intensive care therapy can also serve as a bridge to liver transplantation. Along with decompensation of cirrhosis, the concept of acute-on-chronic liver failure (ACLF) has emerged. This involves an acute precipitating event, such as the development of infection in a patient with cirrhosis, which leads to acute deterioration of hepatic function and extrahepatic organ failure. Extrahepatic complications often include renal, cardiovascular, and respiratory failures. Patients with significant extrahepatic and hepatic failures need ICU admission for organ support. Again, in patients who are deemed suitable liver transplant candidates, intensive care management may allow bridging to liver transplantation. However, patients with a Chronic Liver Failure Consortium ACLF score greater than 70 at 48 to 72 hours post-ICU admission do not seem to benefit from ongoing intensive support and a palliative approach may be more appropriate.

• Acute liver failure
• Acute on chronic liver failure
• Albumin dialysis
• Artificial liver support
• FPSA
• MARS
• Prometheus
• SPAD

• Acute liver failure
• Acute-on-chronic liver failure
• Albumin dialysis
• Extracorporeal liver assist device
• Extracorporeal liver support
• Liver transplantation

Acute-on-chronic hepatitis B liver failure (ACHBLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with cirrhosis, so little is known about the alterations of protein glycopatterns in serum with its development. We aimed to identify the alterations of serum glycopatterns in ACHBLF and probe the possibility of them as novel potential biomarkers for diagnosis of ACHBLF. As a result, there were 18 lectins (e.g., WFA, GSL-II, and PNA) to give significantly alterations of serum glycopatterns in ACHBLF compared with healthy controls (HC) (all p ≤ 0.0386). Meanwhile, among these lectins, there were 12 lectins (e.g., WFA, GAL-II, and EEL) also exhibited significantly alterations of serum glycopatterns in ACHBLF compared with HBV-infected chronic hepatitis (cHB) (all p ≤ 0.0252). The receiver-operating characteristic (ROC) curve analysis indicated there were 5 lectins (PHA-E + L, BS-I, ECA, ACA, and BPL) had the greatest discriminatory power for distinguishing ACHBLF and HC or cHB, respectively (all p ≤ 0.00136). We provided a new basic insight into serum glycopatterns in ACHBLF and investigated the correlation of alterations in serum glycopatterns as novel potential biomarkers for diagnosis of ACHBLF.

• C-reactive protein
• acute-on-chronic liver failure
• artificial liver support system
• double plasma molecular absorption system
• interleukin-6
• procalcitonin
• therapeutic plasma exchange

• anthelmintics parasitology
• hemodialysis renal urinary tract
• small animal critical care
• toxicology
• treatment intoxication

Currently, most acute liver diseases are treated through liver transplantation.

• Acute-on-chronic liver failure
• Decision curve analysis
• Hepatitis B virus
• Logistic regression model
• Model for end-stage liver disease

• Acute-On-Chronic Liver Failure/blood
• Acute-On-Chronic Liver Failure/therapy
• Adult
• Aged
• Clinical Decision-Making/methods
• Female
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/therapy
• Humans
• Liver, Artificial
• Logistic Models
• Male
• Middle Aged
• Models, Statistical
• Regression Analysis
• Retrospective Studies
• Unnecessary Procedures
• Young Adult

• National Natural Science Foundation of China (NSFC)
• Department of Science and Technology, Jiangsu Province, China
• Department of Health, Jiangsu Province, China
• Nantong Science and Technology Bureau, Jiangsu Province, China
• Natural Science Foundation of Jiangsu Province, China

The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.

Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4 % albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.

Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median −68 μmol/L, interquartile range [IQR] −107.5 to −33.5, p = 0.001; SPAD: −59 μmol/L, −84.5 to +36.5, p = 0.001). However, bile acids (MARS: −39 μmol/L, −105.6 to −8.3, p < 0.001; SPAD: −9 μmol/L, −36.9 to +11.4, p = 0.131), creatinine (MARS: −24 μmol/L, −46.5 to −8.0, p < 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L, p = 0.314) and urea (MARS: −0.9 mmol/L, −1.93 to −0.10, p = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10 %, −0.8 to +20.9 %, p < 0.001; SPAD: +7 %, −7.5 to +15.5 %, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.

Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.

German Clinical Trials Register (www.drks.de) DRKS00000371. Registered 8 April 2010.

The online version of this article (doi:10.1186/s13054-015-1159-3) contains supplementary material, which is available to authorized users.

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

• Inflammation
• Hepatic encephalopathy
• Pathogenesis
• Treatment

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/drug therapy
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/metabolism
• Humans
• Inflammation Mediators/antagonists & inhibitors
• Inflammation Mediators/metabolism
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Signal Transduction/drug effects
• Treatment Outcome

• Cirrhosis
• MELD
• Portal Hypertension
• Sepsis
• Survival Scores

• Albumin dialysis
• Cytokine removal
• Extracorporeal organ support
• Liver support

• Acetaminophen
• Acute liver failure
• Albumin
• Endotoxin
• Extracorporeal liver assist device
• Toll-like receptor 4
• UCL-LDD

• Acute liver failure
• Artificial liver system
• Cytokines
• D-Galactosamine
• Liver regeneration

• ACLF
• MERTK
• chronic liver disease
• cirrhosis
• glucocorticoids
• immune dysfunction
• immunomodulation
• infection
• liver failure
• plasma exchange

• Absorption
• Charcoal/chemistry
• Cresols/blood
• Cresols/isolation & purification
• Equipment Design
• Equipment Failure Analysis
• Hemofiltration/instrumentation
• Humans
• Indican/blood
• Indican/isolation & purification
• Interleukin-6/blood
• Interleukin-6/isolation & purification
• Materials Testing
• Membranes, Artificial
• Pilot Projects
• Renal Dialysis/instrumentation
• Sulfuric Acid Esters/blood
• Sulfuric Acid Esters/isolation & purification
• Uremia/blood
• Uremia/prevention & control

• II-LA-1111-20003 Department of Health

• acute-on-chronic hepatitis B liver failure
• interleukin-6
• model for end-stage liver disease
• real-time reverse-transcriptase polymerase chain reaction
• tumour necrosis factor-α
• tumour necrosis factor-α-induced protein-8 like-2

• Albumin dialysis
• Cytokine removal
• Extracorporeal liver support
• Molecular Adsorbents Recirculating System
• Super-large pore membrane

• acute liver failure
• artificial liver support
• drug-induced liver injury
• plasma exchange