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.

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.

Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs

AIM： To characterize and evaluate the therapeutic efficacy of bioartificial liver （BAL） as compared to that of continuous hemodiafiltration （CHDF） with plasma exchange （PE）, which is the current standard therapy for fulminant hepatic failure （FHF） in Japan. METHODS： Pigs with hepatic devascularization were divided into three groups： （1） a non-treatment group （NT; n = 4）; （2） a BAL treatment group （BAL; n = 4）, （3） a PE ＋ CHDF treatment group using 1.5 L of normal porcine plasma with CHDF （PE ＋ CHDF, n -- 4）. Our BAL system consisted of a hollow fiber module with 0.2 i^m pores and 1 × 10^10 of microcarrier-attached hepatocytes inoculated into the extra-fiber space. Each treatment was initiated 4 h after hepatic devascularization. RESULTS： The pigs in the BAL and the PE ＋ CHDF groups survived longer than those in the NT group. The elimination capacity of blood ammonia by both BAL and PE ＋ CHDF was significantly higher than that in NT. Aromatic amino acids （AAA） were selectively eliminated by BAL, whereas both AAA and branched chain amino acids, which are beneficial for life, were eliminated by PE ＋ CHDF. Electrolytes maintenance and acid-base balance were better in the CPE ＋ CHDF group than that in the BAL group. CONCLUSION： Our results suggest that PE ＋ CHDF eliminate all factors regardless of benefits, whereas BAL selectively metabolizes toxic factors such as AAA. However since PE ＋ CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE ＋ CHDF might be more effective for FHF.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-onchronic liver failure:a nationwide prospective multicenter study in China

BACKGROUND： Plasma exchange （PE）-centered artificial liver support system reduced the high mortality rate of hepa titis B virus （HBV）-related acute-on-chronic liver failure （ACLF）. But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.

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.

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

AIM： To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation （OLT）. METHODS： Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system （MARS） as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality （30 d） after OLT. RESULTS： In the 50 patients, the statistically significant improvement in the biochemical parameters was observed （pre-treatment and post-treatment）. Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was： 28 kept alive and 6 patients died. CONCLUSION： Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

Hybrid artificial liver support system for treatment of severe liver failure

AIM: To construct a novel hybrid artificial liver support system (HALSS) and to evaluate its efficacy in patients with severe liver failure.METHODS: Hepatocytes were isolated from suckling pig by the modified Seglen's method. Isolated hepatocytes were cultured in a spinner flask for 24 h to form spheroids before use and the functions of spheroids were detected. HALSS consisted of a plasma separator, a hemo-adsorba and a bioreactor with hepatocytes spheroids in its extra-fiber space.HALSS was applied to 10 patients with severe liver failure.The general condition and the biochemical indexes of the patients were studied just before and after the treatment.RESULTS: The number of cells per liver was about 2-4× 1010 (mean, 3.1 ± 1.5 × 1010). The cell viabilities were more than 95%. After 24 h of spheroid culture, most hepatocytes formed spheroids. The levels of albumin and urea in the medium of spheroid culture were higher than those in supernatant of petri dish culture (P = 0.0015 and 0.0001, respectively). The capacity of albumin production and urea synthesis remained stable for more than one wk and declined rapidly after two weeks in vitro. In HALSS group, the duration of HALSS treatment was 6-10 h each time. All patients tolerated the treatment well without any fatal adverse reaction. After HALSS treatment, the general condition, psychic state, encephalopathy and hepatic function of the patients were improved. The survival rate of the HALSS group, Plasmapheresis group and control group was 30% (3/10), 20% (2/10) and 0% (0/10), respectively (P = 0.024). Two weeks after treatment, Tbil and ALT decreased and the PTA level elevated in HALSS group and pasmapheresis group (Pvalue: 0.015 vs 0.020, 0.009vs 0.012 and 0.032 vs 0.041, respectively). But there was no significant change of blood albumin concentration before and after treatment in HAlSS group and Plasmapheresis group.CONCLUSION: The HALSS established by us is effective in supporting liver function of patients with severe liver failure.

Artificial liver support in pigs with acetaminophen-induced acute liver failure

AIM To establish a reversible porcine model of acute liver failure(ALF) and treat it with an artificial liver system. METHODS Sixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen(APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group(n = 11), in which a treatment procedure was performed, or a control group(n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed. RESULTS Twenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased(P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h(at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group(P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution.Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment(P < 0.05). CONCLUSION This model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system(ZHj-3) is safe and effective for the APAP-induced porcine ALF model.

Artificial liver support molecular adsorbents recirculating system therapy as a bridge to re-transplantation in two cases of long anhepatic duration

BACKGROUND: Molecular adsorbents recirculating sys- tem (MARS) liver support therapy is the development of albumin dialysis. This study was to assess the successful ap- plication of MARS artificial liver support therapy as a bridge to re-transplantation in two cases of long anhepatic duration. METHODS: MARS therapy was given after failure plasma- exchange ( PE) treatment, which resulted in circulatory de- rangement and acute renal dysfunction in a 36-year-old male patient. Finally his uncontrolled anhepatic condition led to a successful re-transplantation. In another 48-year- old man who was diagnosed as having primary nonfunction (PNF) during the liver transplantation, 10-hour MARS treatment contributed to smooth bridging of his anhepatic phase. RESULTS: The two anhepatic patients were bridged for 26 and 17 hours respectively to re-transplantation with MARS therapy. CONCLUSION: Our experience proves that MARS artifi- cial liver can be an effective support for long time bridging PNF until re-transplantation is available.

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.

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure

AIM: To evaluate the efficacy and safety of the TECA-I bioartificial liver support system (BALSS) in treating canines with acute liver failure (ALF). METHODS: Ten canines with ALF induced by 80% liver resection received BALSS treatment (BALSS group). Blood was perfused through a hollow fiber tube containing 1X10(10) porcine hepatocytes.Four canines with ALF were treated with BALSS without porcine hepatocytes (control group), and five canines with ALF received drug treatment (drug group). Each treatment lasted 6 hours. RESULTS: BALSS treatment yielded beneficial effects for partial liver resection induced ALF canines with survival and decreased plasma ammonia, ALT, AST and BIL. There was an obvious decrease in PT level and increase in PA level, and there were no changes in the count of lymphocytes, immunoglobulins (IgA, IgG and IgM) and complement (C3 and C4) levels after BALSS treatment. In contrast, for the canines with ALF in non-hepatocyte BALSS group (control group) and drug group, there were no significant changes in ammonia, ALT, AST, BIL, PT and PA levels. ALF canines in BALSS group, control group and drug group lived respectively an average time of 108.0h +/- 12.0h, 24.0h +/- 6.0h and 20.4h +/- 6.4h,and three canines with ALF survived in BALSS group. CONCLUSION: TECA-I BALSS is efficacious and safe for ALF canines induced by partial liver resection.

TECA hybrid artificial liver support system in treatment of acute liver failure

AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1-2) x 10(10) were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0 degrees C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between the plasma and porcine liver cells. Each treatment lasted 6.0-7.0 h. Physiological and biochemical parameters were measured before,during and after the treatment. RESULTS: The average of porcine liver cells was (1.0-3.0) x 10(10) obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85%-93% by trypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70%-85%. At the end of TECA-HALSS treatment, the levels of plasma NH(3), ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment.One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K(+), Na(+) and Cl(-)) were stable without thrombosis and bleeding in all the six patients. CONCLUSION: TECA-HALSS treatment could be a rapid, safe and efficacious method to provide temporary liver support for patients with ALF.

Liver transplantation and artificial liver support in fulminant hepatic failure

INTRODUCTIONFulminant hepatic failure(FHF)is a severe disease with devastating consequences;the incidence is high in China.Before the availability of liver transplantation,the mortality rate was more than 80%[1,2].The advent of liver transplantation revolutionized the outcome of FHF[3,4].However,many patients were unwilling to accept liver transplantation until very late,hence most of them died because of donor shortage and urgency of the disease[5-7],To overcome he problems,we performed orthotopic liver transplantation(OLT)in combination with artificial liver support(ALS) in the treatment of FHF in the past 2 years with satisfactory results.Our experience was reported below.

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.

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.

Treatment of hepatic failure with artificial liver support system

Objective To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. Methods 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). Results 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease.Conclusion ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.