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Recreational polypharmacy intoxication is a popular trend, particularly among adolescents and young adults. Acute liver failure is an uncommon complication of drug intoxication and has been described separately among patients intoxicated with ethanol, cocaine, and 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy). Many patients with acute liver failure will die without liver transplant, and management of drug-induced acute liver failure is complicated by the fact that polysubstance abuse may be a contraindication for liver transplant, even among young patients. Here we report a case of acute liver failure in an adolescent male secondary to recreational intoxication with ethanol, cocaine, and ecstasy. This patient was not a candidate for liver transplantation. We describe successful treatment using a molecular adsorbent recirculating system (MARS®) or "liver dialysis" and review the literature pertaining to management options for this type of patient.

Post hepatectomy liver failure (PHLF) comprises of a conundrum of symptoms and signs following major hepatic resections. The pathophysiology essentially revolves around disruption of the normal hepatocyte regeneration and disturbed liver homeostasis. Prompt identification of the pre-operative predictors of PHLF in the form of biochemical parameters and imaging features are of paramount importance for any hepatic surgeon and forms the cornerstone of its management. Treatment revolves around a goal-directed resuscitation of the systemic organ failure. Auxiliary support systems such as liver dialysis devices and stem cell therapy are still under investigational trials for treatment of the same. Orthotopic liver transplantation (OLT) is the last resort in most cases not responding to other measures., Highlights • Understanding the mechanics and pathophysiology of post hepatectomy liver failure and its implications in management. • Preventive strategies essential for all liver surgeons. • Overview of assessing clinical severity and management algorithm of PHLF.

Acute liver failure (ALF) is a rare but life-threatening illness with multiple organ failure. The short-term mortality rate exceeded 80 % despite modern approaches in treatment. Drugs, infections by hepatic viruses and toxins are the most common causes of ALF. Progressive jaundice, coagulation disorder and hepatic encephalopathy are dominated as a clinical signs of the illness. We present a case of a 36-year-old Caucasian woman hospitalized in ICU due to yellow discoloration of the skin and sclera, severe disseminated coagulopathy and hemodynamic instability. ALF is developed due to Hepatitis B Virus infection, resulting in hepatic toxicity as well as coma. General condition rapidly improved after applying of Molecular Adsorbent Recirculating System (MARS), an extracorporeal liver support system based on albumin dialysis. It is relatively expensive treatment that is used for the patient with hepatic encephalopathy grade 3 or 4 in our institution. In conclusion, an early administration of MARS significantly reveals subjective and objective clinical improvement in the case we presented.

Background Liver dialysis, molecular adsorbent recirculating system (MARS) particularly, has been used in liver failure to bridge to transplantation. We expanded the indication for MARS to patients with acute shock liver failure and cardiopulmonary failure on extracorporeal membrane oxygenation (ECMO), aiming to improve survival to wean from ECMO. Methods Retrospective chart analysis of patients on ECMO between 2010 and 2015 found 28 patients who met the criteria for acute liver failure, diagnosed by hyperbilirubinemia (total bilirubin ≥10 mg/dl) or by elevated transaminase (alanine transaminase >1,000 IU/liter). Of these patients, 14 underwent MARS treatment (Group M), and 14 were supported with optimal medical treatment without MARS (Group C). Patient characteristics, liver function, and survival were compared between groups. Results Demographics, clinical risk factors, and pre-ECMO laboratory data were identical between the groups. MARS was used continuously for 8 days ± 9 in Group M. Total bilirubin, alanine transaminase, and international normalized ratio were improved significantly in Group M. There were no MARS-related complications. Survival to wean from ECMO for Group M was 64% (9/14) vs 21% (3/14) for Group C ( p = 0.02). Mortality related to worsening liver dysfunction during ECMO was 40% (2/5 deaths) in Group M and 100% (11/11 deaths) in Group C ( p = 0.004). The 30-day survival after ECMO was 43% (6/14) in Group M and 14% (2/14) in Group C ( p = 0.09). Conclusions MARS therapy in patients on ECMO safely accelerated recovery of liver function and improved survival to wean from ECMO, without increasing complications.

Aims: To establish the safety and efficacy of regional citrate anticoagulation (RCA) for pediatric liver failure (LF) patients receiving extracorporeal liver support (ELS) with albumin-assisted dialysis. Methods: Retrospective review of pediatric LF patients receiving ELS from April 2014 to December 2016 at a tertiary children’s hospital pediatric intensive care unit. Demographic and ELS data collected by chart review. Citrate accumulation (CA) was defined as total calcium (mmol/L): ionized calcium (mmol/L) > 2.5 (tCa:iCa). Efficacy was assessed by treatment duration. Safety was assessed by adverse events: bleeding, hemodynamic instability, arrhythmias, unplanned treatment discontinuation. Results: Fifteen patients (median age 3 [interquartile range (IQR) 0.7–8.0]) received 108 ELS treatments (median 5 [IQR 4–7.5]). Sixty-eight episodes of CA were identified. Of those, 6 coincided with intervention and 1 coincided with ELS discontinuation. There were no deaths attributed to ELS or RCA. Conclusion: RCA provides safe and effective anticoagulation for pediatric LF patients requiring ELS.

For more than 10 years, children at our national center for pediatric liver transplantation (LT) have been treated with Molecular Adsorbent Recirculating System (MARS) liver dialysis as a bridging therapy to high-urgency LT. Treatment was reserved for 20 patients with the highest degrees of hepatic encephalopathy (HE; median grade?=?3.5). Death from neurological sequelae was considered imminent for these patients, and this was further reflected in significantly higher international normalized ratios and ammonia levels and worse prognostic liver indices (Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores and liver injury units) in comparison with 32 wait-listed patients who did not receive MARS dialysis. MARS therapy was generally well tolerated, with a reduction in thrombocytes and hemorrhaging as the most common side effects. HE improvement was documented in 30% of the treated patients, but progression to grade IV encephalopathy occurred in 45% of the patients despite the treatment. Serum ammonia, bilirubin, bile acid, and creatinine levels significantly decreased during treatment. Eighty percent of MARS-treated patients survived to undergo LT, and their survival was equivalent to that of non-MARS-treated patients with severe liver failure (69%, P?=?0.52). The heterogeneity between MARS-treated patients and non-MARS-treated patients in our cohort precluded a statistical evaluation of a benefit from MARS for patient survival. Our data demonstrate the safety of MARS even in the most severely ill patients awaiting LT, but strategies that promote the more rapid and widespread availability of high-quality donor organs remain of critical importance for improving patient survival in cases of severe acute liver failure.? 2015 American Association for the Study of Liver Diseases.

Background & Aims In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure. Methods Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n = 9); Acetaminophen plus Control Device (n = 7); and Control plus Control Device (n = 4). Device treatment was initiated two h after onset of irreversible acute liver failure. Results The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio = 0.33, p = 0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p = 0.046); 54% reduction in overall severity of endotoxaemia (p = 0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen. Conclusions The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients.

Review question/objective The purpose of this systematic review is to present the best available evidence for the use of disaccharides versus no treatment in the medical management of minimal hepatic encephalopathy. The objectives of this review are to identify effective medical management strategies for the prevention of minimal hepatic encephalopathy (MHE) and also minimize the adverse clinical manifestations of minimal hepatic encephalopathy. Inclusion criteria Types of participants Studies of adult patients, 18 years and older, with the diagnosis of minimal hepatic encephalopathy in both ambulatory and acute care hospital settings will be included in the review. Transplant patients and patients who have undergone transjugular intrahepatic portosystemic shunt (TIPS) will be excluded. Patients undergoing liver dialysis procedures will also be excluded as they may have other comorbidities that affect their overall treatment plan. Pregnant women will also be excluded in the search. Types of intervention(s) This review will consider studies that evaluate optimal medical management of minimal hepatic encephalopathy strategies. The interventions of interest will be the use of disaccharides to manage the patient with minimal hepatic encephalopathy. Types of outcomes This review will consider studies that include the following outcome measures: psychometric measures, health-related quality of life measures and motor skills. More specifically these include outcomes associated with general care strategies: nutrition, hydration and electrolyte status, as well as safety (due to neuro-cognitive indicators), and in acute illness will measure prevention of coma (lowered blood ammonia levels).

not available Northern International Medical College Journal Vol.10(1) Jul 2018: 324-325

Bei ca. 1 % der Deutschen liegt eine Leberzirrhose vor. Hierbei sollte zwischen der kompensierten und der dekompensierten Leberzirrhose mit einer deutlich schlechteren Prognose unterschieden werden. Als dekompensierte Leberzirrhose bezeichnet man das Auftreten von klinisch relevanten Komplikationen und Folgeerscheinungen der portalen hypertension (wie Aszites, Varizenblutung, hepatische Enzephalopathie und das hepatorenales Syndron) sowie des zunehmenden Leberversagens. Ein optimales intensiv-medizinisches Management ist bei Patienten mit einer dekompensierten Leberzirrhose von einer prognostisch auserordentlichen Bedeutung.

Background Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of “liver dialysis”. During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. Methods Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. Results The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. Conclusions This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.

Pediatric acute liver failure is a rare condition. One third of patients recover with standard medical therapy (SMT); the remaining children require liver transplantation (LTx). To bridge the time to LTx, extracorporeal liver support (ELS) is often needed. Several different ELS systems are available: plasma exchange (PE) in combination with hemodialysis (HD), single-pass albumin dialysis, molecular adsorbent recirculating system (MARS), and the Prometheus(R) Therapy System. In adults, ELS improves cholestasis, portal hypertension, hemodynamic instability, and hepatic encephalopathy; however, no consistent benefit on patient survival has been demonstrated. Of note, underlying diseases are heterogenous and differ substantially between adults and children.

Chronic dialysis patients frequently present with necrotic skin lesions. The differential diagnoses are broad and complex. The main focus of this paper is differentiating features of two diagnostic entities: Warfarin induced skin necrosis and calciphylaxis as early recognition and treatment may prevent the significant mortality. We discuss a case involving a hemodialysis patient, who developed necrotic skin lesions over her thighs and gluteal areas shortly after restarting warfarin for atrial fibrillation without heparin bridging therapy. Incisional biopsies and pathology report were consistent with warfarin induced skin necrosis. Significant improvement of the lesions following discontinuation of Warfarin was also confirming the diagnosis of Warfarin Induced Skin Necrosis.

In their article in Critical Care, Sponholz et al. [1] compared two devices: the molecular adsorbent recirculating system (MARS) and single pass albumin dialysis (SPAD). As Sponholz et al. claim, SPAD is not an effective method for achieving a significant decrease in the concentration of bile acids, creatinine or urea, because a single SPAD procedure induces a 7.62 % (median) reduction in the level of bile acids and an increase in the concentrations of creatinine and urea by respectively 5.04 % (median) and 4.69 % (median), compared with pre-dialysis levels [1]. In contrast, our as yet unpublished study demonstrates that SPAD can effectively reduce not only the level of bile acids but also the concentration of ammonia. Based on our study, the application of the SPAD method with a dialysate flow rate of 1000 ml/h for a total of around 10 h reduces the level of bile acids by 21.9 % (median) and ammonia by 16.25 % (median). A question arises as to the possible causes of such discrepancies. Since continuous venovenous haemodialysis was performed in both studies, the divergence cannot be attributed to the technique. In our view, this divergence is associated with several factors. One of these factors is the difference in dialysate flow rate. An albumin dialysate flow rate of 700 ml/h is highly insufficient. Taking into consideration the results obtained by Sponholz et al., an increase in the albumin dialysate flow rate to at least 1000 ml/h appears to be a necessary precondition to ensure effective elimination of bile acids. Also, the methodology adopted for the study is questionable. In our opinion, comparing the effectiveness of urea and creatinine elimination at radically different dialysate flow rates (SPAD 700 ml/h vs MARS 2000 ml/h) is unjustified and may lead to erroneous conclusions, which in fact occurred [1]. Differences in efficacy between the MARS and SPAD procedures reported in the article in question may also be related to inappropriately selected haemofilters in the extracorporeal blood purification systems under comparison. Furthermore, Sponholz et al. [1] pointed out metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anticoagulation. In our view, increasing the dialysate flow rate would significantly contribute to preventing the irregularities noted in the study. On the other hand, we believe that the risk of citrate overdose during liver dialysis, but also during continuous venovenous haemodialysis, is very low [2–4]. In our medical centre, we have been successfully performing continuous venovenous haemodialysis procedures with regional citrate anticoagulation in patients with severe liver dysfunction, sometimes for up to several weeks. We have never noted any symptoms of overdose apart from end-stage liver failure.

Summerskill-Walshe-Tygstrup syndrome is a rare benign chronic liver disease characterized by recurring cholestasis with jaundice and severe pruritus. Due to insufficient conservative treatment, liver dialysis by Prometheus® was applied to a 45-year-old female patient with resistant pruritus. Initially, other possible liver diseases were excluded and the patient was treated symptomatically since the diagnosis of Summerskill-Walshe-Tygstrup was stated in 1998. As conservative and endoscopic methods progressively failed to relieve the patient's suffering, Prometheus® liver dialysis was performed regularly since 2006 at 3-month intervals and successfully led to a decrease in the patient's symptoms. Cholestatic liver enzymes and also serum bile acids could be lowered significantly from an average of 22.5 ± 2.7 to 7.3 ± 1.7 μmol/l. Consequently, Prometheus® liver dialysis may be a beneficial option for patients with benign recurrent intrahepatic cholestasis suffering from therapy-resistant symptoms and may be used as well as other extracorporeal liver support devices which have already been reported to improve cholestatic pruritus. Copyright © 2012 S. Karger AG, Basel.

Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes.

Hepatic encephalopathy occurs as a complication of alcoholic liver disease may require methods of dialysis available in intensive care units. There is described the case of a 27-year-old patient with jaundice and hepatic encephalopathy with long history of alcohol dependence and substance abuse. The patient was successfully treated using liver dialysis method (Prometheus® system). Basing on this case it is possible to conclude that use of dialysis liver with Prometheus® may be beneficial in patients with severe course of alcoholic liver disease.

Obesity is a worldwide epidemic and public health crisis associated with severe comorbidity leading to end organ dysfunction and poorer transplant outcome. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplant is considered because of the survival benefit as compared to the wait-listed dialysis patients. In liver transplantation, the benefit of transplant as compared to remaining on the list is obvious because there is no viable liver dialysis at this time.Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed function or nonfunction of the organ.Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs.Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less invasive treatments for metabolic surgery evolve, we are likely to see more patients lose weight before transplant as we continue to strive for improved outcomes.

Patients with liver failure still present a high mortality. It can only be significantly improved by the rare resource of liver transplantation. Extracorporeal liver support devices have been developed to temporarily support liver detoxification. Artificial devices without hepatocytes ("liver dialysis" or "albumin dialysis") are already widely used in Europe. The two best-known systems, MARS and Prometheus, use a different technical approach to remove water-soluble as well as albumin-bound toxins from the blood. In MARS, toxins diffuse along a concentration gradient through an albumin-impermeable membrane into a secondary circuit that is pre-filled with an albumin solution. The albumin is continuously "recycled" inside the secondary circuit by different adsorber and low flux dialysis. In contrast, Prometheus includes an albumin-permeable filter allowing separation of the albumin fraction into the secondary circuit where the albumin-bound toxins are directly removed by two adsorbers. Thereafter, high flux dialysis is performed inside the primary circuit. For both extracorporeal systems, an improvement of hepatic encephalopathy and biochemical markers such as bilirubin is consistently reported. In-vivo comparisons of both systems showed significantly higher extraction capacities for protein-bound and water-soluble substances under Prometheus than under MARS treatment. Possible pathophysiological mechanisms could be a reduction of portal pressure or a removal of vasoactive cytokines. However, only few randomised controlled trials with low patient numbers and conflictive results regarding patient survival exist. Nevertheless, a Cochrane meta-analysis revealed a significant survival benefit for extracorporeal liver support devices in patients with acute-on-chronic liver failure. Other promising indications are severe refractory cholestatic pruritus, intoxication with protein-bound substances and graft dysfunction after liver transplantation. As large randomised controlled multi-center trials are currently underway, better evidence will be available soon to define the clinical role of extracorporeal liver support devices.

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.

Mortality from ingestion of the mushroom Amanita phalloides still remains as high as 8-10%. In critical patients, liver dialysis can bridge the patient to liver transplantation, which may be a lifesaving procedure. We report the use of 13C-methacetin breath test (13C-MBT) in monitoring hepatic function in a case of A. phalloides poisoning.A 33-year-old woman ate mushrooms that she had picked. After 8 h, she developed nausea and vomiting, abdominal cramps, and diarrhea, which lasted for another 24 h. On the third day, features of liver injury were seen. Pharmacologic therapy failed and she underwent liver dialysis on days 4 and 5. A 13C-MBT was used to evaluate hepatic functional reserve before the first and after the second dialysis. A liver transplantation on day 6 was successful.The breath test results showed that at 40 min after substrate ingestion the mean 13C-MBT cumulative oxidation percentage was 10.5 +/- 3.8% in healthy controls, whereas in our patient this parameter decreased from 0.09% on the fourth day to 0.02% on the fifth day.13C-MBT is a simple, non-invasive diagnostic tool which may be useful as a predictor of outcome and as a marker of the severity of liver damage.

In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient’s cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure.

Artificial extracorporeal liver support or 'liver dialysis' has been used in patients with severe liver failure with increasing frequency since the Molecular Adsorbents Recirculating System (MARS), a variant of albumin dialysis, was introduced in 1999. Nevertheless, liver dialysis must still be thought of as experimental because its contribution to improved patient survival has not been proven in large randomized trials. Prometheus is a novel device for fractionated plasma separation via an albumin-permeable filter that was developed to improve removal of albumin-bound toxins. Initial studies have proven clinical use of Prometheus to be feasible and safe. Head-to-head comparisons of Prometheus and MARS have shown treatment with the former to be more efficient with respect to removal of most albumin-bound and water-solved markers. As controlled studies with clinical end points are lacking, it is not known whether the observed greater detoxification capacity of Prometheus will translate into clinical benefit; two small studies indicate that there might be a beneficial effect in hepatic encephalopathy and pruritus. In a recent randomized comparison of MARS and Prometheus, however, hemodynamic improvement was observed in response to MARS, but not Prometheus, treatment. A large randomized controlled trial investigating the effect of Prometheus on survival--the HELIOS study--has been initiated. First results are expected in 2008 and will be crucial to establishing a role for Prometheus in the field of extracorporeal liver support.

Leptospirosis is a re-emerging infectious disease, which may lead to multiple organ failure (MOF)and death.We report the first case of severe leptospirosis complicated with acute renal and liver failure, successfully treated with albumin dialysis--molecular adsorbent recirculating system (MARS). Despite antibiotic therapy, optimum medical supportive treatment and timely initiated haemodialysis, the outcome was complicated by severe liver failure: hepatic encephalopathy grade III, hypoglycemia, prominent hyperbilirubinemia (TBIL 31.3 mg/dl, DBIL 28.6 mg/dl)and hepatic cytolysis (ALT 535 IU/l, AST 179 IU/l) and prolongation of the prothrombine time (68.4 sec). The patient underwent two sesions of albumin dialysis with the MARS procedure with complete recovery of hepatic and renal function.Albumin dialysis may confer a significant survival benefit on patients with leptospirosis-induced acute liver failure (ALF).

Background Left ventricular assist device (LVAD) implants bear the risk of driveline/device infections and technical failures. Methods We assessed clinical outcome in LVAD patients with device-related complications. Group 1 (n = 12) received device exchange (DEx) as destination therapy (DT), group 2 (n = 15) received DEx as a bridge to transplant (BTT), group 3 (n = 34) was allocated to receive high-urgency (HU) heart transplantation (HTx), and group 4 (n = 27) had device-related complications that could only be solved by HTx. Primary endpoint was 1-year overall survival. Results Age and Simplified Acute Physiology Score II differed significantly between groups and were highest in group 1, lowest in group 3. One-year survival in groups 1 to 4 was 66.7, 60.0, 82.4, and 70.4% (p = 0.30). Covariate-adjusted odds ratio of 1-year survival (reference: group 1) was for group 2 = 1.52 (95% confidence interval [CI]: 0.42–5.57), for group 3 = 1.13 (95% CI: 0.28–4.56), and for group 4 = 1.89 (95% CI: 0.51–7.04; p for trend 0.70). Clinical complications (need of mechanical ventilator support, extracorporeal circulatory membrane oxygenation (ECMO) implants, kidney/liver dialysis) were comparable between groups. Conclusion Data indicate similar 1-year clinical outcomes in LVAD patients with device-related complications receiving DEx or HTx.

Background: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. Methods: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n=2), acute on chronic liver failure (n=12), posthepatectomy liver failure (n=4), and posttransplantation allograft failure (n=4). Results: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P

Rationale: Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS™) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS™ liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. Results: A total of 13 patients were treated, and 40 sessions of MARS™ liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS™ was 8 days. Conclusions: MARS™ liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

Fulminant hepatic failure (FHF) carries a high mortality. We aimed to review the prognostic factors and explore the potential role of Liver Dialysis (LD). Fifty-two patients were reviewed. The etiologies were acetaminophen toxicity (33%), viral hepatitis (18%), autoimmune (10%), idiosyncratic drug reactions (8%), others (6%) and undetermined (25%). Patients with acetaminophen had a significantly higher survival compared to the non-acetaminophen group (p=0.04). Patients with grade 3 encephalopathy had a mortality of 68%, among 5 patients with grade IV encephalopathy, 2 survived and both had had treatment with LD. Chi-square with Fisher's exact test was used for statistical analysis. Our study confirmed that the diagnosis of non-acetaminophen induced FHF and reduced initial serum factor V level are associated with fatal outcome. Timely OLT significantly improved the survival. The role of LD in hepatic regeneration or as a bridge to OLT needs to be further studied with prospective control trials.

OBJECTIVES: Episodic (acute) type C hepatic encephalopathy (AHE) fails to respond to 5 days of medical therapy in 10-30% of patients and carries a 10-30% mortality rate. We prospectively studied extracorporeal liver support for AHE failing to respond to medical therapy to assess its safety and efficacy and the role of anticoagulation. METHODS: A series of patients with cirrhosis and AHE failing to respond to at least 24 h of medical therapy underwent a maximum of three 6-h charcoal-based hemodiabsorption (Liver Dialysis Unit) treatments. A standard anticoagulation protocol, with heparin dosing based on activated clotting time (ACT) determinations, heparin dose-response curve, and target ACT of 275-300 s, was developed. Therapy was terminated if patients met a predetermined clinical response, deteriorated, or underwent transplantation. RESULTS: Eighteen patients with grade 2-4 AHE despite 5.9 +/- 3.9 days of medical therapy underwent a mean of 1.6 treatments. In 2.6 +/- 1.9 days, 16 patients (88.9%) improved to less than grade 2 HE or achieved at least a 50% hepatic encephalopathy index (HEI) reduction. Median mental status (grade 2 vs 1, p < 0.05) and HEI (0.634 +/- 0.194 vs 0.363 +/- 0.263, p < 0.005) improved significantly. Survival was 94.4% and 72.2% at 5 and 30 days, respectively. Use of our developed anticoagulation protocol resulted in less platelet (14.2% +/- 2.8% vs 32.5% +/- 5.8%, p < 0.005) and fibrinogen consumption (12.1% +/- 3.5% vs 43.3% +/- 8.6%, p < 0.0005) and blood product use (6.2 +/- 1.8 vs 19.0 +/- 5.6 units, p < 0.05) compared with treatments according to manufacturer's guidelines. CONCLUSIONS: Charcoal-based hemodiabsorption treatments in which a standardized anticoagulation protocol is used is safe and effective treatment for AHE not responding to standard medical therapy.

Objective of this study was to determine 1-year survival, costs and cost-effectiveness of the artificial liver support system Molecular Adsorbent Recirculating System (MARS) in patients with acute-on-chronic liver failure (ACLF) and an underlying alcoholic liver disease. In a case-control study, 13 patients treated with MARS were compared to 23 controls of similar age, sex and severity of disease. Inpatient hospital costs data were extracted from patients' files and hospital's internal costing. Patients and treating GPs were contacted, thus determining resource use and survival 1-year after treatment. Mean 1-year survival time in MARS group was 261 days and 148 days in controls. Kaplan-Meier analysis shows advantages of MARS patients (Logrank: P=0.057). Direct medical costs per patient for initial hospital stay and 1-year follow-up from a payer's perspective were Euro 18,792 for MARS patients and Euro 9638 for controls. The costs per life-year gained are Euro 29,719 (time horizon 1 year). From a societal perspective, the numbers are higher (costs per life-year gained: Euro 79,075), mainly because of the fact that there is no regular reimbursement of MARS and therefore intervention costs were not calculated from payer's perspective. A trade-off between medical benefit and higher costs has to be made, but 1-year results suggest an acceptable cost-effectiveness of MARS. Prolonging the time horizon and including indirect costs, which will be done in future research, would probably improve cost-effectiveness.

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P < .05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Objectives: The short-term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here. Study design: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 µmol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis. Preliminary results: MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P

Tricyclic overdose can be a medical emergency, and therapy with intravenous bicarbonate is not always successful in preventing cardiac toxicity or coma. Mortality in patients developing these complications is from 1% to 15%. Extracorporeal detoxification with sorbents has been used in treatment of patients with very high drug levels and declining clinical condition. Ten patients with serious drug overdose caused by tricyclics failed to respond quickly to standard therapy and were in stage 3-4 encephalopathy. Nine of these patients were on respirator support, 5 had hypotension, and 6 had QRS widening. Average level was 1,423 microg/L at presentation. Enteral activated charcoal and intravenous (IV) bicarbonate were initiated in the emergency room. The patients were treated for 3 to 4 hours with the Liver Dialysis Unit, a hemodiabsorption device using a cellulosic plate dialyzer and sorbent suspension as dialysate. Inflow and outflow blood levels indicated that the hemodetoxifier removed modest amounts of the tricyclics, metabolites, and other consumed drugs. The clinical improvement of the patients was dramatic, with patients reaching stage 0 or 1 encephalopathy during the treatment. Ventilator support was removed at the end of treatment for 3 patients who had not already developed pneumonia, and for others was prolonged up to 48 hours because of pneumonia, rather than mental status. Average length of stay in the intensive care unit (ICU) was 4.8 days (range 1 to 7 days). None of the patients died despite their high risk for ventricular arrhythmias, seizures, and death. Clinical improvement may have been attributable to removal of free drug from the blood or to removal of drug metabolites.

Despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%-75% in several studies. In addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are often present. Analogous to artificial kidney treatment in patients with renal failure, an artificial liver assist device is needed not only to bridge patients with fulminant hepatic failure to liver transplantation or own liver regeneration, but also to improve the quality of life of patients with chronic liver insufficiency. Several modalities of artificial liver support are under investigation, like plasma exchange, haemodialysis, haemadsorption, albumin dialysis, liver cell transplantation, and the bioartificial liver. Artificial livers based on only supportive detoxification function do not show significant improvement of survival in controlled studies. Bioartificial liver support systems have also the potential to support hepatic synthetic functions. Bioreactors can be charged with freshly isolated or cryopreserved porcine hepatocytes, but also by human hepatoma cell lines. Several uncontrolled studies in humans show safety of such a treatment, even by using porcine cells. Transmission of porcine endogenous retrovirus to recipients has not been found. Furthermore, beneficial effects have been reported on symptoms of hepatic encephalopathy, on the height of intracranial pressure and on hemodynamic parameters. By using porcine cells immunological problems (e.g., serum sickness) can be expected during treatments longer than one week. However, "proof of the pudding" in the sense of improvement of survival is not yet available. The creation of a "liver dialysis unit" in the near future depends mainly on the development of well-differentiated immortalized human hepatocytes. Some progress in this field has already been obtained.

Extracorporeal detoxification has been proposed to treat patients with hepatic encephalopathy (HE) not responding to standard therapy. To investigate the biocompatibility of a cuprophane charcoal-based detoxification device, a prospective, randomized, controlled study was performed. Of 41 consecutive patients with cirrhosis and HE grade II or III who did not improve with conventional treatment, 20 patients (median age, 56 years; range, 33 to 71 years; 13 men) were randomly assigned to either ongoing conventional treatment or one additional 6-hour treatment with a sorbent suspension dialysis system. Main outcome parameters were physiological function and blood parameters of biocompatibility. In the 10 patients undergoing combined conventional and sorbent suspension dialysis treatment, blood pressure remained unchanged and body temperature and heart rate increased (P:0.01). Platelet count decreased (medians, from 75 to 26 g/L; P:0.001) and international normalized ratio increased after combined treatment (2.0 to 2.2; P:0.001). Three patients developed bleeding complications during treatment or shortly after. Treated patients showed increases in levels of plasma elastase (104 to 586 microg/L; P: = 0.001), tumor necrosis factor-alpha (5.4 to 7.5 pg/mL; P: = 0.04), and interleukin-6 (118 to 139 pg/mL; P: = 0.04), but not interferon-gamma and E-selectin. No changes were observed in the 10 patients treated conventionally. In conclusion, despite technical refinements compared with charcoal hemoperfusion, biocompatibility of sorbent suspension dialysis is still very limited. Clinical complications were apparently caused by blood-membrane interactions and disseminated intravascular coagulation. We suggest further developments in design and appropriate strategies of anticoagulation to improve the biocompatibility of artificial liver support.

Fulminant liver failure is an uncommon but life-threatening complication of severe dengue infection. Molecular adsorbent recirculating system (MARS), which reverses hepatic encephalopathy, is an emerging important element in the armamentarium of organ support in the intensive care unit in patients suffering from acute liver failure. We report an intensive care unit case of fulminant liver failure secondary to dengue hemorrhagic fever, which was supported with MARS. MARS led to rapid reversal of biochemical profile and encephalopathy, resulting in early extubation and intensive care unit discharge.

Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients.

Effects of n-butanol fraction of Gongronema latifolium leave extract on some liver function and histological parameters in CCl4-induced oxidative damage in Wistar albino rats were assessed. Fifty-four (54) Wistar albino rats were divided into treatment group and LD50 groups. Group A (normal control) was given feed and water, Group B (vehicle control) was injected with olive oil intraperitoneally, while the rest groups (C, D, E, F and G) were injected intraperitoneally with a single dose of CCl4 (148 mg/kg) as a 1:1 (v/v) solution in olive oil and all the animals were fasted for 36 hours. This was repeated once every week for a period of four (4) weeks. At the end of 28 days of treatment, liver marker enzymes studies showed that there was significant (p 0.05) difference of these liver marker enzymes and bilirubin levels between the normal control and induced treated groups. Antioxidant assay on the liver homogenate showed that there was significant (p 0.05) difference between the normal control and induced treated groups. These findings suggested that n-butanol fraction of methanolic leave extract of G. latifolium may have anti-hepatotoxic and antioxidative effects against CCl4-induced liver damage in rats.

Objectives: The recurrence of HCV post liver transplantation endangers patient and graft survival. The aim of this study is to analyze the risk factors for HCV recurrence, the effect of the recurrence and its management on the outcome of liver transplantation. Materials and methods: After exclusion of the 6 months mortality, dual HCV and HCC patients, about fifty five HCV related LDLT patients were enrolled in the study and were followed up from 6 to 60 months. Demographic, preoperative, intraoperative and postoperative data were studies. HCV recurrence was defined by elevated transaminases, positive serum HCV RNA and liver biopsy findings. Univariate and multivariate analysis were done on all data to detect the favoring factors of HCV recurrence. Results: HCV recurrence occurred in 21/55 of the patients and one of them developed cirrhosis on follow up. By univariate analysis; CMV infection, mean operative time (12.490 ± 1.8952), acute cellular rejection and pulse steroids treatment were predictors of HCV recurrence (P

Background: Surgical Hepatic resection has been considered as the first-line treatment which is most effective and radical treatment for hepatocellular carcinoma in cirrhotic liver. However, hepatic resection, in the presence of cirrhosis is associated with high risk of hemorrhage; thus, good clinical results can only be achieved by minimizing operative blood loss. The tremendous progress in microwave technology has recently attracted considerable attention. Here we describe the treatment outcomes achieved at our institution for intraoperative use of the microwave tissue precoagulation in hepatic resection as part of our strategy for the treatment of HCC. Methods: Twenty-six selected patients received elective hepatic resections using intraoperative microwave tissue precoagulation as their initial therapy for hepatocellular carcinoma in cirrhotic liver. The patients who were enrolled for our study were chosen according to the Barcelona criteria for HCC management. The safety, therapeutic effect and recurrence were prospectively evaluated and analyzed. Results: All the procedures were completed as planned. The median duration of the operation was 118 (range, 65-250) minutes with a median resection time of 45 (range 30-80) minutes. The median blood loss for resection was 165 (range, 100-750) mL. One patient required blood transfusion. The average time taken to coagulate the anticipated liver transection plane was less than 15 min. There was no operative mortality. The median postoperative hospital stay was 6 days. The median follow-up of patients was 14 months. At last follow up, recurrent tumors were noted in three (11.5%) of the patients (local in one and remote in two of the patients). Conclusion: Our initial results show that surgical microwave tissue precoagulation in liver resection for hepatocellular carcinoma in cirrhotic liver is safe and effective treatment. It achieves an acceptable recurrence rate. Longer follow-up is required to determine the long-term outcome of this new treatment modality.

Klebsiella pneumoniae liver abscess (KLA) is an emerging infectious liver disease in developed countries such as the United States. This is particularly common in the East Asians living in the United States who has other comorbid medical problems, especially diabetes mellitus. Metastatic infections involving non-contiguous areas originating from Klebsiella pneumoniae liver abscess have been documented as being the causal source for endophthalmitis, brain abscess, lung abscess, psoas abscess, splenic abscess and septic arthritis. The incidence of metastatic infection in the setting of KLA is higher than in liver abscesses of any other bacterial origin.

Objective: Image-guided microwave coagulation therapy as a minimally invasive technique has been widely used for the treatment of small HCC in patients who have high surgical risks. However, tumor residual after thermal albation is still the main reason of HCC recurrence. Laparoscopic resection of the tumor after thermal ablation will take advantage of reducing the risk of tumor residual without increasing the risk of hepatic failure. The aim of this study was to evaluate the feasibility and safety of this technique. Methods: From 2008 to 2010, 18 patients (15 men and 3 women; age range, 35-77 years) with HCC and associated severe liver cirrhosis underwent microwave coagulation therapy combined with laparoscopic liver resection. Inclusion criteria were solitary, peripheral or subcapsular HCC lesions localised to the left or anterior right segments; lesion size less than 4 cm; Child-Pugh grading class B or class C. Mortality, morbidity and recurrence rates were analyzed. Results: A total of 18 patients were included. There was no conversion to open operation. The mean operation time was 105 min (range, 70~155 min) and the mean blood loss during operation was 95 ml (range, 40~160 ml). No patient needed blood transfusion. The complications after operation included: pneumonia in 1 patient and mild transient jaundice in 2 patients (

Adrenal Insufficiency (AI), defined as deficient production or action of glucocorticoids resulting from either a structural damage of adrenal glands (primary adrenal insufficiency) or an impairment of the hypothalamic-pituitary axis (secondary adrenal disease), is being reported with increasing frequency in patients with liver disease, and some authors proposed the term “hepato-adrenal syndrome”. The prevalence of AI in patients with liver disease varies widely according to the study population: critically ill patients (33-92%), stable cirrhosis (31-60%), or decompensated cirrhosis, such as variceal bleeding (30-48%) and ascites (26-64%). However there is no current consensus about diagnostic criteria to define AI in patients with liver disease, and its prognostic relevance in stable cirrhosis is still unclear.

Background: Liver cirrhosis is a major cause of death in many developed countries. Binge drinking has been shown to increase the risk of liver cirrhosis. Objective: The aim of this study was to examine the aggregate-level relation between the alcohol consumption and liver cirrhosis mortality rates in Russia. Method: Age-standardized sex-specific male and female liver cirrhosis mortality data for the period 1970- 2005 and data on overall alcohol consumption were analyzed by means ARIMA (Autoregressive Integrated Moving Average) time series analysis. Results: Alcohol consumption was significantly associated with both male and female liver cirrhosis mortality rates: a 1 liter increase in overall alcohol consumption would result in a 7.0% increase in the male liver cirrhosis mortality rate and in 6.2% increase in the female mortality rate. The results of the analysis suggest that 61.4% of all male liver cirrhosis deaths and 56.4% female deaths in Russia could be attributed to alcohol. Conclusions: The outcomes of this study provide support for the hypothesis that alcohol is an important contributor to the liver cirrhosis mortality rate in Russian Federation. The findings from the present study have important implications in regards alcohol-related mortality prevention indicating that a restrictive alcohol policy can be considered as an effective measure of prevention in countries with higher rate of alcohol consumption.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a commonly used antibiotic that has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and one or more major organ involvement. Although rare, TMP-SMZ is a recognised cause of fulminant hepatic failure. We report a 17-year-old Chinese male adolescent who presented with fever, myalgia, generalised maculopapular rash and lymphadenopathy after taking TMP-SMZ for acne vulgaris. He subsequently developed hepatic encephalopathy and was worked up for urgent liver transplantation. He responded well to extracorporeal liver dialysis (originally intended as a bridging therapy) and subsequently recovered without the need for liver transplantation. This case report highlights the importance of early recognition of TMP-SMZ-induced DRESS syndrome and the need for early discontinuation of the drug in the affected patient. Extracorporeal liver dialysis and transplantation should be considered in the management of TMP-SMZ-induced fulminant hepatic failure.

Liver failure, especially in its acute form, is a medical emergency that quickly leads to failure of multiple other organs. Many of these end-organ failures can be supported temporarily by drugs or medical devices, but the support is invariably short-lived if liver function is not restored. In most instances, liver function can only be restored by transplantation, although patients with acute disease have the potential to recover by regeneration ("spontaneous recovery"). Unfortunately, spontaneous recovery from acute liver failure is uncommon, so the two most important aspects of patient management are highly skilled intensive care and early recognition of patients in need of liver transplantation. Even under these circumstances, the mortality of liver failure remains high because we have no easy way of replacing liver function on demand and donor organs are becoming increasingly difficult to obtain in time. The development of techniques for liver assist offer the possibility that patients with liver failure will become a simple management problem, analogous to the options available in the treatment of acute and chronic renal failure.