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.

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.

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.

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.

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.

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.

Liver transplantation in China: problems and their solutions

BACKGROUND: The past decade has witnessed the rapid development of liver transplantation in China. The 1-year survival of liver transplant patients comes to 80% in many leading medical centers and the number of liver transplanta- tion is increasing. However, liver transplantation in China is facing several challenges including recipient with hepato- cellular carcinoma (HCC), recurrence of HCC and hepati- tis B, long-term postoperative care, the bridge to liver transplantation, and shortage of liver donor. This review was to understand the status of and problems in liver trans- plantation in China. DATA RESOURCES: An English-language literature search using MEDLINE (1990-2003) on liver transplantation and other related reports and review articles in Chinese from major transplant centers in China. RESULTS: HCC is one of the main indications for liver transplantation in China but different centers adopted dif- ferent criteria for selection of patients. Hepatitis B virus re- infection is a vital problem after liver transplantation in HBV-related patients. More and more attention was fo- cused on long-term postoperative care and donor shortage. Artificial liver support system has been applied in patients waiting for a graft in many centers. CONCLUSIONS: HCC remains to be one of the main indi- cations for liver transplantation in China; combined hepati- tis B immune globulin and lamivudine is considered effec- tive to prevent hepatitis B virus reinfection. Apart from long-term postoperative care for the improvement of the survival rate, early steroid withdrawal is feasible in liver transplantation. Living donor liver transplantation, split liv- er transplantation, and marginal donor transplantation can deal with donor shortage to some extent. Artificial liver as- sist system serves as a bridge to liver transplantation.

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.

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 liver transplantation for acute hepatic failure:asingle-center experience

BACKGROUND:Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate.The outcome of AHF varies with etiology,but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients.This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease.METHODS:A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center.We analyzed and compared the etiology,outcome,prognosis,and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group.RESULTS:AHF was due to viral hepatitis in 25 patients (52.1%;hepatitis B virus in 22),drug or toxic reactions in 14 (29.2%;acetaminophen in 6),Wilson disease in 4 (8.3%),unknown reasons in 3 (6.3%),and miscellaneous conditions in 2 (4.2%).In the LT group,36 patients (7 underwent living donor LT,and 29 cadaveric LT) had an average model for endstage liver disease score (MELD) of 35.7.Twenty-eight patients survived with good graft function after a follow-up of 27.3± 4.5 months.During the waiting time,6 patients were treated with ALSS and 2 of them died during hospitalization.The 30-day,12-month,and 18-month survival rates were 77.8%,72.2%,and 66.7%,respectively.In the N-LT group,12 patients had an average MELD score of 34.5.Four patients were treated with ALSS and all died during hospitalization.The 90-day and 1-year survival rates were only 16.7% and 8.3%,respectively.CONCLUSIONS:Hepatitis is the most prominent cause of AHF at our center.Most patients with AHF,who fulfill the Kings College Criteria for LT,did not survive longer without LT.ALSS did not improve the prognosis of AHF patients,but may extend the waiting time for a donor.Currently,LT is still the most effective way to improve the prognosis of AHF patients.

Acute liver failure:individualization of care and minimizing the need for liver transplantation

Acute liver failure(ALF)is a challenging condition that requires a rapid transfer and management in a specialized intensive care unit affiliated to a transplant center.The outcome depends mainly on patient’s age,etiology of ALF,severity of the neurological damage at time of presentation,systemic and brain hemodynamic status and the possibility of a rapid access to liver transplantation(LT).Nevertheless,in recent years,the global survival rate improved and the number of patients with ALF who do not require LT have significantly increased.Between 1998 and 2013,the gap of improvement was respectively 12%and 25%(1).

Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

The role of the high mobility group box 1 （HMGB-1） in acute hepatic failure and the effect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） levels were detected by the enzyme linked immunosorbent assay （ELISA）, the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system （P〈0.05）. It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

Therapeutic application of molecular adsorbents recirculating system in various pathogenic MODS/MOF patients

Multiple organ dysfunction syndrome (MODS) or multiple organ failure ( MOF)is a syndrome which is frequently related to shock and sepsis, and has been described as the mostcommon cause of death in the noncoronary critical care unit. The potential pathogenesis of theseptic and systemic inflammatory response syndrome (SIRS) response has been increasingly associatedwith the development and aggravation of MODS or MOF. And studies in this respect have alsodemonstrated that there is a higher risk of mortality associated with some specific organ systemswhen they are dysfunctional, thus leading to the failures of the liver, brain, lung, and kidney. Theliver interacts with many other organ systems, and liver dysfunction may act collectively in theproduction of organ system dysfunction, thus finally ending up with MODS. The management of patientswith MODS/MOF is predominantly supportive and some specific treatments are directed at treating theunderlying disorders. The molecular adsorbent recirculating system (MARS) is an albumin dialysissystem and it was shown to be efficient in removing both hydrosoluble substances and stronglyalbumin-bound substances, so that it improves not only the function of the liver but also that ofother organ systems, and it can be applied to treating the diseased liver as the cause of multipleorgan failure and actively combat deterioration in patients' liver function. This trial aims atevaluating the therapeutic effectiveness of MARS in 39 various pathogenic MODS patients in ourhospital and Beijing Ditan Hospital.