Extracorporeal Liver Support Systems Research Articles

Efficacy of therapeutic plasma exchange in pediatric cases of acute liver failure as an extracorporeal liver support system

BackgroundAcute liver failure in the pediatric population is often accompanied by deranged metabolism, severe encephalopathy and coagulopathy. A liver transplant is the most viable option for the management of such patients. Therapeutic plasma exchange (TPE) is helpful in improving the liver biochemistry profile, thereby, increasing their likelihood of undergoing a liver transplant MethodThe study was conducted over a period of 3 years (January 2018 to December 2021). Indications mainly consisted of ALF with hepatic encephalopathy, worsening liver parameters in spite of medical management, and candidacy for undergoing a liver transplant. Plasma exchange was performed daily or alternatively until the patient recovered, succumbed, or was stable enough to undergo a transplant. Biochemical parameters serum bilirubin, ALT, AST serum ammonia serum urea, serum creatinine were recorded before and after TPE sessions. ResultsThe study group comprised 14 patients of which a total of 28 TPE was performed. There were a total of 5 cases of cryptogenic ALF, 4 of Wilson disease, 2 cases each of infection-related ALF and autoimmune hepatitis, and a single case of drug-induced hepatitis. A total of 5 out of 14 patients underwent a liver transplant and amongst the 9 who did not undergo a transplant, 4 patients expired due to septic shock syndrome; the remaining 5 were discharged in a stable condition following TPE sessions. The disease-free survival was 78.9% and the transplant-free survival was 35.71%. ConclusionTPE plays a crucial role in improving the biochemistry profile of the liver in children with liver failure.

Two adolescent cases of early use of Molecular Adsorbent Recirculating System<sup>®</sup> for drug-induced fulminant hepatic failure

Fulminant hepatic failure (FHF) is a rare but fatal disease with a 40%-80% mortality, often requiring liver transplantation, which is hard to perform in children. A therapeutic intervention alternative to liver transplantation is an extracorporeal artificial liver support system. Molecular Adsorbent Recirculation Systems® (MARS) has emerged as a bridge therapy for adult FHF, whereas in pediatric FHF, there have been a small number of cases of implementing MARS. Recently, we witnessed the recovery of 2 teenagers with FHFs caused by acetaminophen and a diet aid. Both patients were treated uneventfully, with early use of MARS. These cases suggest that early use of MARS may be a promising therapeutic intervention in pediatric drug-induced FHF.

Extracorporeal liver support techniques: a comparison.

ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.

Extracorporeal liver support and liver transplantation for acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is defined by acute decompensation, organ failure and a high risk of short-term mortality. This condition is characterized by an overwhelming systemic inflammatory response. Despite treating the precipitating event, intensive monitoring and organ support, clinical deterioration can occur with very poor outcomes. During the last decades, several extracorporeal liver support systems have been developed to try to reduce ongoing liver injury and provide an improved environment for the liver to regenerate or as a bridging therapy until liver transplantation. Several clinical trials have been performed to evaluate the clinical efficacy of extracorporeal liver support systems, but no clear impact on survival has been proven. DIALIVE is a novel extracorporeal liver support device that has been built to specifically address the pathophysiological derangements responsible for the development of ACLF by replacing dysfunctional albumin and removing pathogen and damage-associated molecular patterns (PAMPs and DAMPs). In phase II clinical trial, DIALIVE appears to be safe, and it seems to be associated with a faster time to the resolution of ACLF compared with standard medical treatment. Even in patients with severe ACLF, liver transplantation saves lives and there is clear evidence of transplant benefit. Careful selection of patients is required to attain good results from liver transplantation, but many questions remain unanswered. In this review, we describe the current perspectives on the use of extracorporeal liver support and liver transplantation for ACLF patients.

Selection Liver Transplantation and Bridge Therapeutic Modalities in Acute Liver Failure

Introduction: Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. Therefore, different extracorporeal liver support systems have been developed to function as a bridge to transplantation or spontaneous survival. Conversely, the shortage of organs demands a rigorous selection process to determine whom should receive transplantation and several prognostic models have been proposed to identify the patients who would benefit the most from liver transplantation (LT). Objectives: A review of the main selection criteria used for LT in ALF is carried out, focusing mostly on the new proposed prognostic markers, and aiming to identify poor prognosis criteria associated with futility in LT. Extracorporeal liver support systems (ECLS) were also reviewed, including an analysis of their impact on the survival of patients with ALF. Methods: MEDLINE and PubMed databases were searched between 16th October 2021 and 5th December 2021. The inclusion criteria were: adult patients; patients with acute liver injury (ALI) or ALF; observational studies; clinical studies; case series; case-control studies; systematic reviews; meta-analysis. Discussion: King’s College criteria (KCC) have been widely used and despite good specificity, have low sensitivity. Several markers have been used to improve prognostic accuracy, but the results are not sufficiently clear. Patient age, ABO incompatibility, and poor-quality grafting were potential factors that could indicate potential futility in LT. ECLS have a positive influence in clinical and laboratory parameters; however, there is no clear evidence of improvement in survival. Conclusion: ALF is a heterogeneous syndrome, which brings into question of the studies carried out to evaluate prognostic criteria to select patients for LT. It also narrows down the studies performed to evaluate the impact of ECLS on survival.

Bio-Artificial Liver Support System: A Prospective Future Therapy

Whether acute or chronic, liver failure is a state of liver dysfunction that can progress to multiorgan failure. Mortality in liver failure patients is approximately 80–90% and is caused by detoxification failure, which triggers other immediate complications, such as encephalopathy, coagulopathy, jaundice, cholestasis, and acute kidney failure. The ideal treatment for liver failure is liver transplantation, but the long waiting period for the right donor match causes unavoidable deaths in most patients. Therefore, new therapies, such as tissue engineering, hepatocyte transplantation, and stem cells, are now being studied to anticipate the patient’s condition while waiting for liver transplantation. This literature review investigated the effectiveness of some bio-artificial liver support systems using review methods systematically from international publication sites, including PubMed, using keywords, such as bio-artificial liver, acute and chronic liver failure, extracorporeal liver support system (ECLS), MARS, single-pass albumin dialysis (SPAD). Artificial and bioartificial liver systems can show specific detoxification abilities and pathophysiological improvements in liver failure patients but cannot reach the ideal criteria for actual liver function. The liver support system must provide the metabolic and synthetic function as in the actual liver while reducing the pathophysiological changes in liver failure. Aspects of safety, cost efficiency, and practicality are also considered. Identifying the technology to produce high-quality hepatocytes on a big scale is essential as a medium to replace failing liver cells. An increase in detoxification capacity and therapeutic effectiveness must also focus on patient survival and the ability to perform liver transplantation.

The Use of Extracorporeal Liver Support Systems In Acute Decompensated Liver Failure

The aim of the study: to evaluate the efficacy of extracorporeal liver support systems in patients with acute liver failure of various etiologies.Material and methods. The study included 117 patients with acute liver failure of various etiologies. The main group consisted of 71 patients who received complex intensive therapy, including MARS-therapy and hemodiafiltration. The comparison group included 46 patients who received albumin dialysis (24 patients) and hemodiafiltration (22 patients) alone. The mean age of the patients was 34±5.6 years, the majority (56.4%) were men. Dynamic assessment of patients' severity was performed using Sequential Organ Failure Assessment (SOFA) and Model for End-Stage Liver Disease (MELD) scales.Results. A more significant reduction of SOFA and MELD scores was noted as early as by day 10 of intensive therapy in the main group with sequential use of extracorporeal liver detoxification methods — to 2.7±0.2 vs. 8.3±0.5 points (P=0.021) on SOFA and to 16.7±0.4 vs. 23.4±1.4 points (P=0.023) MELD scales. The use of a comprehensive approach to extracorporeal detoxification in acute decompensated liver failure increased the regression rate of multiple organ failure from 51.2 to 74.6% and reduced mortality from 47.8 to 25.4% (χ2=6.266; df=1; P=0.013). At the same time, the cumulative proportion of survivors depending on the type of complication within 30 days was 88.4% in the main group and 69.0% in the comparison group (χ2=4.164; df=1; P=0.042).Conclusion. A comprehensive approach to extracorporeal detoxification is highly effective, providing a more significant reduction of SOFA and MELD scores, increasing the proportion of regression of multiple organ dysfunction and reducing mortality.

The use of a single pass albumin dialysis for the management of liver failure

Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.

From activated charcoal to selective plasma exchange: A retrospective analysis of mushroom poisoning cases treated in the intensive care unit

Introduction: This study aims to evaluate presenting symptoms, clinical and laboratory findings, and treatment modalities of adult patients presenting with mushroom poisoning treated in the intensive care unit (ICU) with special consideration of extracorporeal liver support systems.
 Materials and methods: Records of patients with mushroom poisoning treated in the ICU between January 2007 and December 2014 were analyzed retrospectively.
 Results: Sixteen adult patients were treated in the ICU for mushroom poisoning during the designated study period. Presentation to the hospital was most common during October of each year. Average time from ingestion of mushrooms to first symptoms was 17.81 hours, and to ICU admission was 2.38 days. The most common symptoms were nausea, vomiting and diarrhea. The most common laboratory finding was elevation of liver transaminases. In cases with elevated liver transaminases, penicillin G, silibinin and N-acetyl cysteine were used. Extracorporeal support systems were used in 9 cases. Two cases underwent emergency liver transplantation.
 Conclusion: Liver transplantation is the most definitive and effective treatment in indicated cases of mushroom poisoning. Extracorporeal support systems should be considered in the early period both as a treatmet modality on their own or to save time until the definitive treatment is possible. The question of which extracorporeal detoxification technique to use is difficult to answer and controlled clinical trials which compare their efficacy are needed.

Impact of anion exchange adsorbents on regional citrate anticoagulation.

Introduction:Heparin and citrate are commonly used anticoagulants in membrane/adsorption based extracorporeal liver support systems. However, anion exchange resins employed for the removal of negatively charged target molecules including bilirubin may also deplete these anticoagulants due to their negative charge. The aim of this study was to evaluate the adsorption of citrate by anion exchange resins and the impact on extracorporeal Ca2+ concentrations.Methods:Liver support treatments were simulated in vitro. Citrate and Ca2+ concentrations were measured pre and post albumin filter as well as pre and post adsorbents. In addition, batch experiments were performed to quantify citrate adsorption.Results:Pre albumin filter target Ca2+ concentrations were reached well with only minor deviations. Citrate was adsorbed by anion exchange resins, resulting in a higher Ca2+ concentration downstream of the adsorbent cartridges during the first hour of treatment.Conclusions:The anion exchange resin depletes citrate, leading to an increased Ca2+ concentration in the extracorporeal circuit, which may cause an increased risk of clotting during the first hour of treatment. An increase of citrate infusion during the first hour of treatment should therefore be considered to compensate for the adsorption of citrate.

Comparison of selective plasma exchange and plasmadialfiltration with MARS and Prometheus systems in the treatment of liver failure

The mortality of patients with hepatic failure remains high. Often the patient's life can be saved only with extracorporeal liver support (ELS). ELS systems – MARS® и Prometheus® have proved their efficacy but their widespread use is constrained by their very high cost. Introduction in clinical practice of new affordable ELS systems is a topical issue. The objective: to compare clinical and laboratory effects of selective plasma exchange (SPE), plasmadialfiltration (PDF) with use of the selective membrane plasma separators EvaclioTM and MARS® and Prometheus® (FPSA) systems in the treatment of liver failure. Subjects and methods: 15 extracorporeal procedures of each type were performed in 52 patients with acute liver failure (14) and acute-on-chronic liver failure (38): MARS, FPSA, PDF, SPE with use of Evaclio ЕС-2C, and ЕС-3C, ЕС-4C. The clinical and laboratory parameters (total, direct and indirect bilirubin, total protein, albumin, creatinine, urea, etc.), severity of the condition according to MELD score were determined before and after the session and the next morning. Changes, side effects and complications of procedures were assessed and compared. Results. Reduction of concentration of direct bilirubin was comparable with FPSA, PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (38-42%), indirect bilirubin – with PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (29-34%). Low-molecular metabolites (urea, creatinine) were better removed with FPSA (35-44%) and PDF (40-42%). The reduction of their concentration with SPE was insignificant. The reduction of albumin level was the highest with FPSA (10.2%) and SPE on Evaclio ЕС-4C20 (14.3%). All investigated ELS methods did not exert a significant influence on the basic parameters of blood coagulation and quantity of blood cells. No side effects and complications were observed. Conclusion: Selective plasma exchange and plasmadiafiltration are generally comparable in clinical and laboratory effects in the treatment of liver failure with MARS and Prometheus system provided significantly lower costs.

Update on extracorporeal liver support.

Extracorporeal liver support (ELS) is a large unmet need in day-to-day hepatology practice. In an era of ever-improving outcomes with liver transplantation for very sick patients with either acute liver failure (ALF) or acute-on-chronic liver failure, the outcomes for similar patients who are ineligible for transplantation remains poor. Providing a bridge to recovery from these catastrophic conditions is the aim of ELS, and we aim to review the evidence to date of different ELS devices as well as look to the future of ELS device development. Studies on different ELS devices shave been relatively consistent in their inability to demonstrate a survival benefit; however, recent published evidence has suggested ways in which the three key pillars to ELS - the disease (patient selection), device (ELS system), and dose (intensity) - may be modified to attain a more positive outcome. New devices are grasping these concepts and demonstrating encouraging preclinical results. ELS devices to studied to date have not been able to significantly improve transplant-free survival. Newer ELS devices are currently in clinical trials and their results are awaited.

A bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers.

The bioartificial liver (BAL) device is an extracorporeal liver support system incorporating living hepatocytes. A major problem in BAL device development is to obtain a high number of functional cells. In this study, we focused on a genetically engineered mouse hepatoma cell line, Hepa/8F5, in which elevated liver functions are induced via overexpression of liver-enriched transcription factors activated by doxycycline (Dox) addition. We applied a three-dimensional culture technique using hollow fibers (HFs) to Hepa/8F5 cells. Hepa/8F5 cells responded to Dox addition by reducing their proliferative activity and performing liver-specific functions of ammonia removal and albumin secretion. The functional activities of cells depended on the timing of Dox addition. We also found that Hepa/8F5 cells in the HF culture were highly functional in a low rather than high cell density environment. We further fabricated an HF-type bioreactor with immobilized Hepa/8F5 cells as a BAL device. Although ammonia removal activity of this BAL device was lower than that of the small-scale HF bundle, albumin secretion activity was slightly higher. These results indicated that the BAL device with immobilized Hepa/8F5 cells was highly functional with potential to show curative effects in liver failure treatment.

Quantifying changes in innate immune function following liver transplantation for chronic liver disease

BackgroundLiver transplantation (LT) offers patients with cirrhosis long-term survival, however many die from sepsis whilst awaiting LT. The liver's role in innate immunity may be key to improving outcomes, but the immune effects of LT have not been quantified. MethodsInnate immune capacity was assessed by clearance of 99mTc-Albumin nanospheres in patients with chronic liver failure before and after LT. ResultsTwenty-eight patients with chronic liver disease on the LT waiting list entered the study during the twelve-month study period and nine patients underwent LT and completed the study protocol. One patient developed hepatic artery thrombosis in <7 days and was excluded from the study. Innate immune function was significantly impaired in patients with chronic liver disease on the LT waiting list and this was directly correlated with MELD score. LT normalised innate immune function by day 1 post LT with further improvement occurring by day 7 post LT. Donor liver weight was the only factor correlated with innate immune function at day 1 post LT but this effect was negated by day 7 post LT. ConclusionRecognising the immune effects of LT may facilitate treatment of cirrhosis and inform development of extracorporeal liver support systems.

Clinical effectiveness of MARS treatment - multidirectional analysis of positive clinical response to treatment.

Aim of the studyLiver failure is a life-threatening condition which often requires intensive care treatment. It is essential to quickly determine whether there are indications for extracorporeal liver support systems for the patient. The aims of the study were: to assess effectiveness of molecular adsorbent recirculating system (MARS) therapy based on selected clinical criteria, to analyze the moment of clinical response and to create a patient’s profile, who will benefit clinically from the treatment.Material and methodsThe analysis encompassed medical histories of 65 patients treated with MARS. Effectiveness of treatment was evaluated based on selected clinical parameters. Statistical analysis was performed based on medical data gathered.ResultsThere were 158 cycles of MARS performed, with effectiveness documented in 57 cycles (36.6%). The first MARS session was effective in 43.1% of patients. They also more often responded to the second cycle (63.6% vs. 15.4%). A significant part of the analysis was devoted to create a profile of the patient in whom positive response can be expected. A low MELD score and low baseline white blood cells (WBC) level are statistically significant factors in multivariate analysis of selected features of positive clinical response to treatment.ConclusionsMARS therapy is an effective form of treatment in a properly selected group of patients with liver failure. The first MARS session is the most effective one. It is also a good prognostic factor for further clinical response to treatment. Multifactorial analysis of positive clinical response to treatment enables to create a patient’s profile based on the lower baseline MELD score and WBC.

Emerging Role of Extracorporeal Support in Acute and Acute-on-Chronic Liver Failure: Recent Developments

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are life-threatening illnesses requiring intensive care admission and potentially liver transplantation. Artificial extracorporeal liver support (ECLS) systems remove water-soluble and albumin-bound toxins to maintain normal serum chemistry, prevent further hepatic/organ system damage, and create an environment for potential hepatic regeneration/recovery (ALF) or bridge to liver transplantation (ALF and ACLF). Use of artificial ECLS has been studied in both ALF and ACLF. Artificial ECLS systems have been found to be safe and have demonstrated the following benefits: improvement of biochemistries, hemodynamic status, and hepatic encephalopathy. Despite this, only one prospective randomized controlled trial examining the use of high-volume plasma exchange has demonstrated improvement in transplant-free survival. Bioartificial (cell-based) ECLS systems build on the technology of artificial systems, incorporating living hepatocytes in a bioactive platform to further mimic endogenous hepatic detoxification and synthetic functions. Currently, no bioartificial system has been found to confer a mortality benefit; however, these platforms offer the greatest potential for future development.

1. Development of bioengineered xenogeneic decellularized humanized liver for the development of extracorporeal liver for the treatment of acute liver failure

Background and Aims: Acute as well as chronic liver failures are major fatal problems, which lead up to 60–80% mortality every year. In acute condition, systemic inflammation and accumulation of toxic compounds (ammonia) in liver results in multi-organ failure which leads to hepatic encephalopathy. Liver transplantation is limited due to timely unavailability of enough donors, post-transplantation complications and high cost involvement. The present study demonstrates a promising strategy of using bioartificial extracorporeal liver support system prepared through decellularization and repopulation of xenogenic liver with human hepatic progenitor cells (hHPCs). Methods: Xenogenic liver was decellularized by perfusion method using retrograde change of detergents and other chemicals. Removal of nuclear components, retention of ECM and vascular integrity of whole decellularized liver was identified. DiD-labeled hHPCs were infused to identify the cells distribution and engraftment efficiency. Repopulation of hHPCs within the decellularized liver scaffold was determined by SEM analysis whereas the functional activity of repopulated cells was determined by ammonia detoxification experiment by urea quantification. Results: The decellularized liver vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. Repopulated hHPCs showed homogeneous distribution within the decellularized liver scaffold showing defined vascular tree with multiple branching and residual niches of proliferating cells. Ammonia detoxification showed the functional activity and future applicability of repopulated humanized liver scaffold as extra-corporeal natural organ support system. Conclusions: This study demonstrate an innovative technology for bioengineering humanized extra- corporeal liver system as better approach for ammonia detoxification as temporary support to the failing liver. The authors have none to declare.

Applying the Molecular Adsorbent Recirculating System (MARS) in the Treatment of Acute Liver Failure (ALF) Case Report

Abstract 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.

Acute liver failure

Acute liver failure (ALF) is a life threatening condition defined by the evidence of hepatic injury, jaundice, coagulopathy, and encephalopathy in a patient without preexisting cirrhosis and with an illness duration of &lt;26 weeks. The etiologies of ALF are heterogeneous: viral hepatitis being the most common in the East, whereas drug-induced, particularly acetaminophen, being the most common in the West. Over the past decades, the outcomes of ALF have been improving with early recognition and prompt initiation of etiology-specific therapy (especially N-acetylcysteine), complex intensive care protocols and urgent liver transplantation (LT). The most commonly used prognostic scoring systems include King’s College Criteria (more specific) and MELD (more sensitive). Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality in the early phase; hypertonic saline is suggested for patients with high-risk for developing intracranial hypertension (ICH) and when ICH develops, mannitol is recommended as first-line therapy. Bacterial and fungal infections are very common necessitating strict preventive measures, careful surveillance and prompt aggressive antimicrobial therapy. Acute kidney injury develops in 50-70% of patients; mostly reversible in survivors and temporary dialysis is required in about 30% of cases. Overall 1-year survival after LT has been reported to be lower in patients with ALF as compared to those with cirrhosis; however following the first year this trend has been to be reversed and ALF patients have a better long-term survival. Extracorporeal liver support system, such as albumin dialysis and plasmapheresis, may serve as a bridge to LT and may increase LT-free survival in select cases.&#x0D; Figure 1 CT brain ของผู้ป่วยเพศหญิง อายุ 22 ปี มีภาวะ ตับวายเฉียบพลันจากยา แรกรับมี encephalopathy grade III CT brain พบ mild cerebral edema with loss of sulci and gyri, blurring of grey - white junctions and mild narrowing of ventricles (A) 3 วันหลังเข้ารับการรักษา ในโรงพยาบาล ผู้ป่วยมีอาการแย่ลง encephalopathy grade IV, sluggish pupillary response to light both eyes: CT brain พบ progression of cerebral edema, loss of grey-white junctions and brain herniation (B)&#x0D;

Acute liver failure

Acute liver failure (ALF) is a life threatening condition defined by the evidence of hepatic injury, jaundice, coagulopathy, and encephalopathy in a patient without preexisting cirrhosis and with an illness duration of &lt;26 weeks. The etiologies of ALF are heterogeneous: viral hepatitis being the most common in the East, whereas drug-induced, particularly acetaminophen, being the most common in the West. Over the past decades, the outcomes of ALF have been improving with early recognition and prompt initiation of etiology-specific therapy (especially N-acetylcysteine), complex intensive care protocols and urgent liver transplantation (LT). The most commonly used prognostic scoring systems include King’s College Criteria (more specific) and MELD (more sensitive). Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality in the early phase; hypertonic saline is suggested for patients with high-risk for developing intracranial hypertension (ICH) and when ICH develops, mannitol is recommended as first-line therapy. Bacterial and fungal infections are very common necessitating strict preventive measures, careful surveillance and prompt aggressive antimicrobial therapy. Acute kidney injury develops in 50-70% of patients; mostly reversible in survivors and temporary dialysis is required in about 30% of cases. Overall 1-year survival after LT has been reported to be lower in patients with ALF as compared to those with cirrhosis; however following the first year this trend has been to be reversed and ALF patients have a better long-term survival. Extracorporeal liver support system, such as albumin dialysis and plasmapheresis, may serve as a bridge to LT and may increase LT-free survival in select cases.