• ALF
• ammonia
• artificial liver support
• hepatic encephalopathy
• on-line CHDF

Currently the treatment of choice for critical liver failure is liver transplantation. Liver failure is treated conservatively until a matching liver donor becomes available. The therapeutic plasma exchange (TPE) plays an important role as a bridge to transplantation by removing accumulated toxins from patient plasma, as well as restoring the coagulation profile.

This was a retrospective study on critically ill liver disease patients who underwent TPE from January 2012 to September 2015. The data were collected for the analyses of coagulation parameters, liver function tests, renal function tests, model for end-stage liver disease (MELD) scores, mortality, and hospital stay.

In the study duration, a total of 45 patients with critical liver disease underwent therapeutic plasma exchange. The TPE resulted in a statistically significant reduction in the bilirubin level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time (PT), international normalized ratio (INR), serum ferritin level and MELD scores. Higher MELD scores in both pre- and post-TPE were associated with higher mortality during the hospital stay.

The TPE is safe and well-tolerated, and it improves coagulation profile and liver function tests in critically ill liver disease patients, but the overall survival remains low.

• Acute liver failure
• MELD contributing
• Therapeutic plasma exchange

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.

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

It is thought that a good survival rate of patients with acute liver failure can be achieved by establishing an artificial liver support system that reliably compensates liver function until the liver regenerates or a patient undergoes transplantation. We introduced a new artificial liver support system, on-line hemodiafiltration, in patients with acute liver failure.

This case series study was conducted from May 2001 to October 2008 at the medical intensive care unit of a tertiary care academic medical center. Seventeen consecutive patients who admitted to our hospital presenting with acute liver failure were treated with artificial liver support including daily on-line hemodiafiltration and plasma exchange.

After 4.9 ± 0.7 (mean ± SD) on-line hemodiafiltration sessions, 16 of 17 (94.1%) patients completely recovered from hepatic encephalopathy and maintained consciousness for 16.4 ± 3.4 (7-55) days until discontinuation of artificial liver support (a total of 14.4 ± 2.6 [6-47] on-line hemodiafiltration sessions). Significant correlation was observed between the degree of encephalopathy and number of sessions of on-line HDF required for recovery of consciousness. Of the 16 patients who recovered consciousness, 7 fully recovered and returned to society with no cognitive sequelae, 3 died of complications of acute liver failure except brain edema, and the remaining 6 were candidates for liver transplantation; 2 of them received living-related liver transplantation but 4 died without transplantation after discontinuation of therapy.

On-line hemodiafiltration was effective in patients with acute liver failure, and consciousness was maintained for the duration of artificial liver support, even in those in whom it was considered that hepatic function was completely abolished.

• Actin Cytoskeleton/metabolism
• Albumins/metabolism
• Animals
• Bioreactors
• Cell Aggregation
• Cell Culture Techniques/instrumentation
• Cells, Cultured
• Hepatocytes/metabolism
• Hepatocytes/ultrastructure
• Kinetics
• Male
• Rats
• Rats, Inbred F344
• Rotation
• Spheroids, Cellular
• Stress, Mechanical

• Animals
• Disease Models, Animal
• Liver Failure/therapy
• Liver, Artificial
• Research Design

• Humans
• Liver Failure/therapy
• Liver Transplantation
• Liver, Artificial/trends

AIM: To evaluate whether treatment with the Prometheus^® system significantly affects cytokines, coagulation factors and other plasma proteins.

METHODS: We studied nine patients with acute-on-chronic liver failure and accompanying renal failure. Prometheus^® therapy was performed on 2 consecutive days for up to 6 h in all patients. Several biochemical parameters and blood counts were assessed at regular time points during Prometheus^® treatment.

RESULTS: We observed a significant decrease of both protein-bound (e.g. bile acids) and water-soluble (e.g. ammonia) substances after Prometheus^® therapy. Even though leukocytes increased during treatment (P < 0.01), we found no significant changes of C-reactive protein, interleukin-6, and tumor necrosis factor-α plasma levels (all P  > 0.5). Further, antithrombin 3, factor II and factor V plasma levels did not decrease during Prometheus^® therapy (all P  > 0.5), and the INR remained unchanged (P  = 0.4). Plasma levels of total protein, albumin, and fibrinogen were also not altered during Prometheus^® treatment (all P  > 0.5). Finally, platelet count did not change significantly during therapy (P = 0.6).

CONCLUSION: Despite significant removal of protein-bound and water-soluble substances, Prometheus^® therapy did not affect the level of cytokines, coagulation factors or other plasma proteins. Thus, the filters and adsorbers used in the system are highly effective and specific for water-soluble substances and toxins bound to the albumin fraction.

• Prometheus
• Albumin dialysis
• Extracorporeal system
• Tumor necrosis factor-α
• Interleukin-6
• Coagulation factors
• Fibrinogen

• Blood Coagulation Factors
• Blood Proteins/metabolism
• Equipment Design
• Humans
• Liver Failure/therapy
• Liver, Artificial
• Platelet Count
• Renal Dialysis