The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010. © 2010 Wiley‐Liss, Inc.     

红细胞分布宽度在慢加急性肝衰竭患者预后预测中的应用

目的 旨在探讨红细胞分布宽度（RDW）在慢加急性肝衰竭（ACLF）患者预测预后中的应用。方法 选取乙型肝炎病毒（HBV）相关性ACLF患者78例,根据预后分为生存及死亡组,检测患者外周血RDW水平及其他相关临床指标。结果 ACLF死亡患者外周血RDW水平高于生存患者（t=-3.568,P=0.004）。RDW与白细胞计数（WBC）、中性粒细胞绝对值/淋巴细胞绝对值（NLR）、总胆红素（TBIL）、终末期肝脏病评分（MELD）存在相关性（P值均<0.05）。受试者工作特征曲线（ROC）分析显示：RDW预测ACLF死亡率的ROC曲线下面积（AUC）为0.64,Cut off值为17.15%,灵敏度和特异度分别为54.2%和67.9%。多因素回归分析显示：RDW、NLR、国际标准化比值（INR）是ACLF患者短期死亡率的独立危险因素（OR值=1.444、1.305、1.891,P值均<0.05）,生存分析显示：RDW≥17.15%患者生存率低于RDW＜17.15%患者（P<0.05）。结论 外周血RDW是临床预测ACLF患者短期预后的简单、有效的指标。     

Quality of life following emergency liver transplantation for acute liver failure

INTRODUCTION: Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health-related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. PATIENTS AND METHODS: Data were collected using between-method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF-36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non-parametric t-tests. RESULTS: Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF-36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. CONCLUSION: Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.     

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections(BIs)trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus(HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016.The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4%were community-acquired,46.4%were healthcare-associated,and 40.2%belonged to nosocomial BIs.Pneumonia(40.7%),spontaneous bacterial peritonitis(SBP)(34.5%),and bloodstream infection(BSI)(13.4%)were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend(P=0.021).Sixty-one strains of bacteria,including 83.6%Gramnegative bacteria and 29.5%multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli(44.3%)and Klebsiella pneumoniae(23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend(ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P<0.001).The independent predictors of the 28-d outcomes of patients with HBV-ACLF were COSSH-ACLF score(hazard ratio[HR]=1.371),acute kidney injury(HR=2.187),BSI(HR=2.339),prothrombin activity(HR=0.967),and invasive catheterization(HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.     

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan–Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.     

Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome

BACKGROUND:

Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS).

METHODS:

Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO₂/FiO₂), hepatic function, platelet count, and blood coagulation were determined.

RESULTS:

Significant improvement was observed in HR, MAP, PaO₂/FiO₂, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more significantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were significantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1% (18/31), viral survival rate 36.4% (4/11), and non-viral survival rate 70% (14/20).

CONCLUSION:

Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.KEY WORDS: Severe acute liver failure, Artificial liver, Plasma exchange, Hemoperfusion, Continuous veno-venous hemodiafiltration     

Hyponatremia influences the outcome of patients with acute-on-chronic liver failure: an analysis of the CANONIC study

Introduction

Hyponatremia is a marker of poor prognosis in patients with cirrhosis. This analysis aimed to assess if hyponatremia also has prognostic value in patients with acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality.

Methods

We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,341 consecutive patients admitted to 29 European centers with acute decompensation of cirrhosis (including ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infections, or any combination of these), both with and without associated ACLF (301 and 1,040 respectively).

Results

Of the 301 patients with ACLF, 24.3% had hyponatremia at inclusion compared to 12.3% of 1,040 patients without ACLF (P <0.001). Model for end-stage liver disease, Child-Pugh and chronic liver failure-SOFA scores were significantly higher in patients with ACLF and hyponatremia compared to those without hyponatremia. The presence of hyponatremia (at inclusion or during hospitalization) was a predictive factor of survival both in patients with and without ACLF. The presence of hyponatremia and ACLF was found to have an independent effect on 90-day survival after adjusting for the potential confounders. Hyponatremia in non-ACLF patients nearly doubled the risk (hazard ratio (HR) 1.81 (1.33 to 2.47)) of dying at 90 days. However, when considering patients with both factors (ACLF and hyponatremia) the relative risk of dying at 90 days was significantly higher (HR 6.85 (3.85 to 12.19) than for patients without both factors. Patients with hyponatremia and ACLF had a three-month transplant-free survival of only 35.8% compared to 58.7% in those with ACLF without hyponatremia (P <0.001).

Conclusions

The presence of hyponatremia is an independent predictive factor of survival in patients with ACLF. In cirrhosis, outcome of patients with ACLF is dependent on its association with hyponatremia.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0700-0) contains supplementary material, which is available to authorized users.     

Survival Benefit of Obese Patients With Pulmonary Embolism

ObjectiveTo investigate the impact of obesity and underweight on adverse in-hospital outcomes in pulmonary embolism (PE).Patients and MethodsPatients diagnosed as having PE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification code I26 in the German nationwide inpatient database were stratified for obesity, underweight, and normal weight/overweight (reference group) and compared regarding adverse in-hospital outcomes.ResultsFrom January 1, 2011, through December 31, 2014, 345,831 inpatients (53.3% females) 18 years and older were included in this analysis; 8.6% were obese and 0.5% were underweight. Obese patients were younger (67.0 vs 73.0 years), were more frequently female (60.2% vs 52.7%), had a lower cancer rate (13.6% vs 20.5%), and were more often treated with systemic thrombolysis (6.4% vs 4.3%) and surgical embolectomy (0.3% vs 0.1%) vs the reference group (P<.001 for all). Overall, 51,226 patients (14.8%) died during in-hospital stay. Obese patients had lower mortality (10.9% vs 15.2%; P<.001) vs the reference group and a reduced odds ratio (OR) for in-hospital mortality (OR, 0.74; 95% CI, 0.71-0.77; P<.001) independent of age, sex, comorbidities, and reperfusion therapies. This survival benefit of obese patients was more pronounced in obesity classes I (OR, 0.56; 95% CI, 0.52-0.60; P<.001) and II (OR, 0.63; 95% CI 0.58-0.69; P<.001). Underweight patients had higher prevalence of cancer and higher mortality rates (OR, 1.15; 95% CI, 1.00-1.31; P=.04).ConclusionObesity is associated with decreased in-hospital mortality rates in patients with PE. Although obese patients were more often treated with reperfusion therapies, the survival benefit of obese patients occurred independently of age, sex, comorbidities, and reperfusion treatment.     

Analysis of ECOG performance status in head and neck squamous cell carcinoma patients: association with sociodemographical and clinical factors, and overall survival

Purpose

In the present study, we analyzed sociodemographical and clinical factors, and the Eastern Cooperative Oncology Group performance status (ECOG-PS) scale in head and neck squamous cell carcinoma (HNSCC) patients. We evaluated the impact of a range of variables on overall survival.

Methods

We investigated a sample of HNSCC patients (n?=?671), using sociodemographical and clinical information, and survival data collected from a review of epidemiological, clinical, and treatment reports. Statistical associations were analyzed by bivariate and multivariate statistical tests. Statistical significance was set at p?<?0.05.

Results

Of patients 85.4% recorded good ECOG-PS scores. Poor ECOG-PS scores were associated with the covariates indicative of dysphagia [odd ratios (OR)?=?2.660, CI 95%?=?1.661–4.260, p?=?0.000] and large-size malignant disease (T3–T4; OR?=?5.337, CI 95%?=?2.251–12.652, p?=?0.000). Overall survival analysis revealed that ECOG-PS scores (OR?=?1.879, CI 95%?=?1.162–3.038, p?=?0.010), tumor size (OR?=?1.665, CI 95%?=?1.035–2.680, p?=?0.036), and the presence of cervical metastasis (OR?=?3.145, CI 95%?=?2.008–4.926, p?=?0.000) were independent predictors.

Conclusion

Evaluation of physical consumption in head and neck cancer patients at diagnosis may indicate a more aggressive type of malignant disease. Thus, the ECOG-PS scale may help to identify HNSCC patients in need of rapid referral, who may benefit from specific therapeutic and rehabilitative interventions.     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.     

Acute Pulmonary Embolism During Pregnancy and Puerperium: National Trends and In-Hospital Outcomes

ObjectiveTo investigate the trend and outcomes of acute pulmonary embolism (PE) during pregnancy and puerperium using a large national database.Patients and MethodsThe National Inpatient Sample was queried to identify pregnancy-related hospitalizations in the United States from January 1, 2007, through September 30, 2015. Temporal trends in the rates of acute PE and in-hospital mortality rates were extracted.ResultsAmong 37,524,314 hospitalizations, 6,333 patients (0.02%) had acute PE. The prevalence of comorbidities and risk factors such as hypertension, obesity, and smoking increased, but rates of acute PE did not change significantly (18.01 in 2007 vs 19.36 in 2015, per 100,000 hospitalizations, P_trends=.21). Advanced therapies were used in a small number of women (systemic thrombolysis: 2.4%, surgical pulmonary embolectomy: 0.5%, and inferior vena cava filter in 8.3%). Rates of in-hospital mortality were almost 200-fold higher among those who had acute PE (29.3 vs 0.13, per 1000 pregnancy-related, P<.001). The rate of in-hospital mortality did not change among women with acute PE (2.6% in 2007 vs 2.5% in 2015, P_trends=.74).ConclusionIn this contemporary analysis of pregnancy-related hospitalizations, acute PE was uncommon, but rates have not decreased over the past decade. Acute PE during pregnancy and puerperium was associated with high maternal mortality, and the rates of in-hospital mortality have not improved. Future studies to improve prevention and management of acute PE during pregnancy and puerperium are warranted.     

Heart failure education in the emergency department markedly reduces readmissions in un- and under-insured patients

Background

Heart failure (HF) readmissions are a longstanding national healthcare issue for both hospitals and patients. Our purpose was to evaluate the efficacy of a structured, educational intervention targeted towards un- and under-insured emergency department (ED) HF patients.

Treatment Outcomes and Health Care Resource Utilization in Patients With Newly Diagnosed Multiple Myeloma Receiving Lenalidomide-only Maintenance,Any Maintenance,or No Maintenance: Results from the Connect MM Registry

Purpose

Maintenance therapy after autologous stem cell transplantation (ASCT) improves clinical outcomes in multiple myeloma (MM), but the effect of continued treatment with lenalidomide-only maintenance, or any maintenance, on health care resource utilization (HCRU) is largely unknown.

Relationship Between Etiology of Cirrhosis and Survival Among Patients Hospitalized in Intensive Care Units

ObjectiveTo determine short-term outcomes of patients with alcohol-associated cirrhosis (ALC) admitted to the intensive care unit (ICU) compared with other etiologies of liver disease. In addition, we investigate whether quick sequential organ failure assessment accurately predicts presence of sepsis and in-hospital mortality in critically ill patients with various etiologies of cirrhosis.MethodsA retrospective cohort of 1174 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Outcomes of interest included survival rates within the ICU, post-ICU in-hospital, or at 30 days post-ICU discharge.ResultsFive hundred seventy-eight patients were found to have ALC with 596 in the non-ALC group. There was no significant difference in ICU mortality rates in ALC versus non-ALC cohorts (10.2% vs 11.7%, P=.40). However, patients with ALC had significantly higher post-ICU in-hospital death (10.0% vs 6.5%, P=.04) as well as higher mortality at 30-day post-ICU discharge (18.7% vs 11.2%, P<.001). Sustained alcohol abstinence did not offer survival advantage over nonabstinence. The predictive power for quick sequential organ failure assessment for sepsis and in-hospital mortality for patients with cirrhosis was limited.ConclusionCritically ill patients with ALC have decreased survival after ICU discharge compared with patients with other etiologies of cirrhosis, independent of alcohol abstinence.     

Low hemoglobin levels are associated with direct antiglobulin test positivity in patients with acute-on-chronic liver failure

BackgroundMultiple factors contribute to anemia in patients with Hepatitis B virus (HBV)related acute-on-chronic liver failure (ACLF); however, the mechanism is unclear. The purpose of this study was to evaluate the clinical significance of the direct antiglobulin test (DAT) in patients with HBV related ACLF.MethodsDAT was used to detect immunoglobulins and/or complement proteins on the surface of erythrocytes.ResultsWe recruited 78 HBV-associated ACLF patients, 30 chronic hepatitis B(CHB)patients and 40 healthy people between October 2015 and May 2016. In HBV related ACLF patients, the hemoglobin concentration, number of erythrocytes, and hematocrit value were significantly lower, while the erythrocyte distribution width was significantly higher, compared to patients with CHB and healthy controls (HCs) (P < 0.001). The rates of DAT positivity in HBV related ACLF patients, CHB patients, and HCs were 62.8 %, 13.3 %, and 0%, respectively. DAT-positive ACLF patients exhibited lower Hb levels, older average age, as well as higher total bilirubin, alanine aminotransferase, and complement component 3 levels compared to DAT-negative patients.ConclusionsHBV related ACLF patients showed significant alterations in erythrocyte parameters, possibly reflecting disease development and severity. The high presence of erythrocyte autoantibodies suggested that immunologic clearance of erythrocytes contributed to multifactorial anemia in HBV related ACLF patients.     

Acute liver failure: A review for emergency physicians

Introduction

Acute liver failure (ALF) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization.

The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-l-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH₃ levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.     

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

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

BMSC上清对治疗大鼠急性肝衰竭的临床研究分析

目的：探讨骨髓间充质干细胞（BMSC）上清治疗大鼠急性肝衰竭（ALF）的疗效,为其临床应用提供理论依据。方法采用全骨髓贴壁筛选法培养SD大鼠BMSC并收集其上清。腹腔注射D-氨基半乳糖胺（D-gal）建立大鼠ALF模型;将造模成功的大鼠随机分为治疗组和对照组,分别将等体积的BMSC上清及0.9%氯化钠注射液（NS）腹腔注射治疗3d,比较两组动物的肝功能、肝组织病理改变和7d生存率。结果（1）7d存活率分别为：BMSC上清治疗组70%,对照组20%,有显著差异（P＜0.05）。（2）BMSC上清治疗组的ALT、AST、TBIL明显降低,而对照组肝功能损害无明显改变,二者比较有显著性差异（P〈0.01）。（3）BMSC上清治疗组肝脏病理组织学损害明显改善。结论 BMSC上清腹腔注射治疗可明显改善ALF大鼠的肝功能及肝脏组织学损害,提高ALF大鼠的存活率,为ALF的治疗提供了新的途径。