Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system

BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells

There is currently a pressing need for alternative the-rapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver(BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells(h PSCs). In this mini-review, we summarize previous clinical trials with different BAL systems, and discuss advantages of and potential obstacles to utilizing h PSC-derived hepatic cells in clinical-scale BAL systems.

Establishment of a risk assessment score for deep vein thrombosis after artificial liver support system treatment

BACKGROUND The artificial liver support system(ALSS)is an effective treatment method for liver failure,but it requires deep venous intubation and long-term indwelling catheterization.However,the coagulation mechanism disorder of basic liver failure diseases,and deep venous thrombosis(DVT)often occur.AIM To evaluate the risk factors for DVT following use of an ALSS and establish a risk assessment score.METHODS This study was divided into three stages.In the first stage,the risk factors for DVT were screened and the patient data were collected,including ALSS treatment information;biochemical indices;coagulation and hematology indices;complications;procoagulant use therapy status;and a total of 24 indicators.In the second stage,a risk assessment score for DVT after ALSS treatment was developed.In the third stage,the DVT risk assessment score was validated.RESULTS A total of 232 patients with liver failure treated with ALSS were enrolled in the first stage,including 12 with lower limb DVT.Logistic regression analysis showed that age[odds ratio(OR),1.734;P=0.01],successful catheterization time(OR,1.667;P=0.005),activity status(strict bed rest)(OR,3.049;P=0.005),and D-dimer level(≥500 ng/mL)(OR,5.532;P<0.001)were independent risk factors for DVT.We then established a scoring system for risk factors.In the validation group,a total of 213 patients with liver failure were treated with ALSS,including 14 with lower limb DVT.When the cutoff value of risk assessment was 3,the specificity and sensitivity of the risk assessment score were 88.9%and 85.7%,respectively.CONCLUSION A simple risk assessment scoring system was established for DVT patients with liver failure treated with ALSS and was verified to have good sensitivity and specificity.

Nursing of Artificial Liver Support System in the Treatment of Severe

Objective:Research on nursing method of artificial liver support system applied in severe hepatitis patients.Methods:Selected 50 severe hepatitis patients in our hospital during the period of January 2018 and January 2019,observed and analyzed the clinical intervention effect of all treated by artificial liver support system cooperating with related nursing methods.Results:After the treatment,the clinical symptoms and abdominal distension of the patients were relieved,whose spirit took a turn for the better and the jaundice subsided.Among these patients,68%got improved enough to be released,26.00%gave up for financial concerns and 6.00%died.Before and after treatment,the patients’PT and INR,APTT,TT improved obviously,and the difference were quite a lot(P<0.05),while ALT and ALB showed few without any statistical significance(P>0.05).Conclusion:During the treatment and intervention of severe hepatitis patients with artificial liver support system,effective nursing interventions are needed,mainly including completely preoperative,intraoperative and postoperative care so as to ensure the treatment effect and promote the recovery of intervention,which has remarkable significance to clinical development.

Application Status and Prospect of Bio-artificial Liver

Liver failure which can be caused by viral hepatitis,alcohol,drugs,metabolic diseases,autoimmune processes or other fac tors is the end stage of chronic liver disease.Although liver transplantation is currently considered to be the primary treatment measures of chronic liver disease.Due to donor shortages,surgical complications and immune rejection,cell therapy has been extensively studied.?Hepa tocyte transplantation and artificial liver have evolved into a simpler alternative to liver failure treatment.Artificial liver can be used as Liver replacement therapy in patients who were waiting for the liver transplantation with chronic liver disease.The ideal biological artificial liver must have the liver material metabolism,detoxification,synthesis and secretion and other functions.Nowadays bio-artificial liver has carried out a large number of clinical trials and get some progress.?This article is now discuss the status of bio-artificial liver and its re placement therapy prospects.

Nursing Care of 10 Patients with Vasovagal Reflex Caused by Artificial Liver Support System Treatment

This study outlines the essential nursing strategies employed in the care of 10 patients experiencing vascular vagal reflex, managed with artificial liver support systems. It highlights a holistic nursing approach tailored to the distinct clinical manifestations of these patients. Key interventions included early detection of psychological issues prior to initiating treatment, the implementation of comprehensive health education, meticulous monitoring of vital signs throughout the therapy, prompt emergency interventions when needed, adherence to prescribed medication protocols, and careful post-treatment observations including venous catheter management. Following rigorous treatment and dedicated nursing care, 7 patients demonstrated significant improvement and were subsequently discharged.

Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure

Background and Aims:Nonbiological artificial liver(NBAL)is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF).This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio(CER)of comprehensive medical treatment,plasma exchange(PE),and double plasma molecular adsorption system(DPMAS)plus half-dose PE(DPMAS+PE)in patients with HBV-ACLF.Methods:A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment,PE,or DPMAS+PE and were prospectively evaluated.Patients were divided into four subgroups based on the pretreatment prothrombin activity(PTA):Group I(PTA>40%),group II(PTA 30–40%),group III(PTA 20–30%),and group IV(PTA<20%).The main outcome measures were 28 day effectiveness;90 day liver transplantation-free survival;change of biochemical parameters;and CER.Results:DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure.Clearance of serum total bilirubin(TBIL),AST,and creatinine(Cr)were significantly higher in the DPMAS+PE group than in the PE group.For subjects with group I liver failure,DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness.Conclusions:Compared with comprehensive medical treatment and PE alone,DPMAS with halfdose sequential PE treatment more effectively improved TBIL,AST,and Cr in HBV-ACLF patients,improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure,and was more cost effective.DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.

A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models

The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants.Herein,a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres(KPMs,bilirubin adsorbents)was connected with the principle machine of wearable artificial liver(approximately 9 kg)to treat hyperbilirubinemia beagles for the first time.With the initial normal dose of heparin,the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation.The removal efficiency of the double-deck column for total bilirubin(TBIL)was 31.4%.Interestingly,the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%.The“anticoagulant+column”realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump;however,the proposed principle machine of wearable artificial liver and“anticoagulant+column”cannot completely replace the bio-liver now.The intelligence of the device and the versatility of the adsorbent need to be improved;moreover,advanced experimental techniques need to be developed to validate the survival rates in animals.Overall,this study is a meaningful trial for the development of wearable artificial livers in the future.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.

Combined use of non-biological artif icial 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 artif icial 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:Signifi cant 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 signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.01). Prothrombin time(PT) and albumin were signifi cantly 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 signifi cantly higher in the patients with non-viral liver failure than in those with viral liver failure.

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

AIM To establish a simplified, reproducible D-galactosamineinduced cynomolgus monkey model of acute liver failure having an appropriate treatment window. METHODS Sixteen cynomolgus monkeys were randomly dividedinto four groups(A, B, C and D) after intracranial pressure(ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05(24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded. RESULTS Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBi L, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor(TNF)-α, interleukin(IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups(P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.CONCLUSION We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.

Efficacy of plasma exchange in adjuvant treatment of chronic and acute liver failure

Objective:To study and evaluate the clini1cal effect of plasma exchange in the adjuvant treatment of chronic and acute liver failure.Methods:Totally 60 patients with chronic and acute liver failure in our department were divided into two groups.The control group received comprehensive treatment and the plasma exchange group received plasma exchange.The changes of total bilirubin(TBIL),PT percentage activity(PTA),alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB),interleukin-6(IL-6),procalcitonin(PCT)and C-reactive protein(CRP)were measured after treatment,and were assessed in terms of the degree of relief of clinical symptoms.Results:TBIL,ALB,Alt,AST,IL-6,PCT and CRP in the two groups decreased and PTA increased compared with those before treatment,but the curative effect of the treatment group was better than that of the control group(P<0.05).The total effective rate of the treatment group was 80.0%,which was higher than 46.6%of the treatment group(P<0.05).Conclusion:Plasma exchange can help to improve the liver function,remove a large number of inflammatory factors,promote the recovery of liver function and improve the prognosis of patients with chronic and acute liver failure.

Major liver resections,perioperative issues and posthepatectomy liver failure:A comprehensive update for the anesthesiologist

Significant advances in surgical techniques and relevant medium-and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections.To support these outstanding results and to reduce perioperative complications,anesthesiologists must address and master key perioperative issues(preoperative assessment,proactive intraoperative anesthesia strategies,and implementation of the Enhanced Recovery After Surgery approach).Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate.Among postoperative complications,posthepatectomy liver failure(PHLF)occurs in different grades of severity(A-C)and frequency(9%-30%),and it is the main cause of 90-d postoperative mortality.PHLF,recently redefined with pragmatic clinical criteria and perioperative scores,can be predicted,prevented,or anticipated.This review highlights:(1)The systemic consequences of surgical manipulations anesthesiologistsmust respond to or prevent,to positively impact PHLF(a proactive approach);and(2)the maximal intensivetreatment of PHLF,including artificial options,mainly based,so far,on Acute Liver Failure treatment(s),to buytime waiting for the recovery of the native liver or,when appropriate and in very selected cases,toward livertransplant.Such a clinical context requires a strong commitment to surgeons,anesthesiologists,and intensivists towork together,for a fruitful collaboration in a mandatory clinical continuum.

基于压印细胞片组装的仿生肝小叶

Liver-tissue engineering has proven valuable in treating liver diseases,but the construction of liver tissues with high fidelity remains challenging.Here,we present a novel three-dimensional(3D)-imprinted cell-sheet strategy for the synchronous construction of biomimetic hepatic microtissues with high accuracy in terms of cell type,density,and distribution.To achieve this,the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics dataset.The data and biomimetic hepatic micro-tissues with hexagonal hollow cross-sections indicate that cell information was successfully generated using a homemade 3D-imprinted device for layer-by-layer imprinting and assembling the hepatic cell sheets.By infiltrating vascular endothelial cells into the hollow section of the assembly,biomimetic hepatic microtissues with vascularized channels for nutrient diffusion and drug perfusion can be obtained.We demonstrate that the resultant vascularized biomimetic hepatic micro-tissues can not only be integrated into a microfluidic drug-screening liver-on-a-chip but also assembled into an enlarged physiological structure to promote liver regeneration.We believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.