• Hepatolenticular Degeneration/surgery
• Hepatolenticular Degeneration/diagnosis
• Liver Transplantation/standards
• Liver Transplantation/adverse effects
• Liver Transplantation/methods
• Humans
• Copper
• End Stage Liver Disease/surgery
• End Stage Liver Disease/mortality
• End Stage Liver Disease/diagnosis
• Treatment Outcome
• Patient Selection
• Waiting Lists/mortality
• Liver Failure, Acute/surgery
• Liver Failure, Acute/diagnosis
• Liver Failure, Acute/etiology
• Liver Failure, Acute/mortality
• Liver Cirrhosis/surgery
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis

• cirrhosis
• aclf
• inflammation

• Humans
• Acute-On-Chronic Liver Failure/therapy
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Liver Transplantation
• Multiple Organ Failure/complications
• Syndrome
• Prognosis

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

• Pediatric hepatology
• bleeding
• emergency
• hepatoblastoma
• hyperammonaemia
• inborn errors of metabolism
• infantile cholestasis
• liver hemangioma
• liver trauma
• paediatric acute liver failure
• portal hypertension
• rupture
• variceal bleeding

• Albumin
• Ceruloplasmin
• Metallomics
• α2-macroglobulin

• Animals
• Cattle
• Chromatography, High Pressure Liquid
• Copper
• Female
• Humans
• Ligands
• Mass Spectrometry
• Zinc

• FSBSI FSC BST RAS № FNWZ-2019-0001 Ural Branch, Russian Academy of Sciences
• project No. 078 Russian Science Foundation

The aim of the study was to investigate the surgical timing, results, and advantages of living-donor liver transplantation in patients who underwent liver transplantation due to Wilson’s disease.

The study included Wilson’s patients who underwent liver transplantation and their live donors. Demographic information, preparations for surgery, liver transplant type, grafts used, results, and complications were examined.

Between 2006 and 2020, 29 liver transplants were performed for 27 Wilson’s patients in our clinic. The study included 11 female and 16 male patients, with a mean age of 20.8 ±11.1 years and a mean body mass index of 20.5 ±3.2 kg/m². The mean MELD score of the adult patients was 16.5 ±6.3, and the mean PELD score of the paediatric patients was 19.6 ±17.2. Five patients underwent transplantation due to acute liver failure, and 22 patients with low MELD score had liver transplants due to chronic liver disease. Three patients who were referred with acute liver failure died in the perioperative period; no mortality was observed in the 22 elective patients. The overall survival was calculated as 88.8%. The 1-, 3-, and 5-year survival were 100% among elective early transplanted patients.

Liver transplant is the most effective treatment for liver failure caused by Wilson’ s disease. When performed promptly, living-donor liver transplantation results in high survival rates in cases of both acute liver failure and chronic liver failure, and it no deterioration of the patient’s condition is evident.

• Wilson’s disease
• liver transplantation
• living donor liver transplantation

• artificial
• extracorporeal circulation
• liver
• transplant

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF.

To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.

Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device.

Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01).

The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

• Acute-on-chronic liver failure
• Acute liver failure
• Plasmapheresis
• Plasma exchange
• Liver failure

• Acute-On-Chronic Liver Failure/mortality
• Acute-On-Chronic Liver Failure/therapy
• Hospital Mortality
• Humans
• Liver Failure, Acute/mortality
• Liver Failure, Acute/therapy
• Plasma Exchange/methods
• Randomized Controlled Trials as Topic
• Survival Rate
• Time Factors
• Treatment Outcome

• Albumin dialysis
• Copper toxicity
• Dialysis
• Extracorporeal liver support
• Plasmapheresis
• Wilson disease

• fractionated plasma separation and adsorption
• sequential organ failure assessment
• single pass albumin dialysis

• ATP7B
• Wilson ATPase
• child
• cirrhosis
• copper
• fatty liver
• fulminant hepatic failure
• hepatolenticular degeneration

• Wilson disease
• acute liver failure
• end-stage liver disease
• liver transplant

• Wilson’s disease
• decoppering
• dimercaptopropansulfonate sodium
• fulminant hepatic failure
• therapeutic plasma exchange

Wilson’s disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.

• Wilson’s disease
• Wilson disease
• Chelating agents
• Penicillamine
• Zinc
• Copper
• Orphan disease
• Liver transplantation

Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash^® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF.

In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h.

All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed.

Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

• Contraindications
• Copper
• Indications
• Liver transplantation
• Wilson disease

• Acute Kidney Injury/mortality
• Acute Kidney Injury/therapy
• Adult
• Aged
• Albumins/administration & dosage
• Bilirubin/metabolism
• Creatinine/metabolism
• Dialysis/methods
• Female
• Glutathione Peroxidase/metabolism
• Humans
• Lactic Acid/metabolism
• Male
• Middle Aged
• Prions/metabolism
• Retrospective Studies
• Saccharomyces cerevisiae Proteins/metabolism
• Statistics, Nonparametric
• Young Adult
• gamma-Glutamyltransferase/metabolism