Model selection and curative effect judgment criteria for artificial liver in the treatment of liver failure / 中华肝脏病杂志

Artificial liver is one of the effective methods to treat liver failure. Patients with liver failure are critically ill and have great individualized differences. Therefore, the specific program for the treatment of liver failure with artificial liver should be individualized. The commonly used non-biological artificial liver models include simple plasmapheresis, double filtration plasmapheresis, plasma filtration with dialysis, double plasma molecular adsorption system, molecular absorbent recirculating system, hemodiafiltration, continuous venovenous hemodiafiltration, hybrid, etc. The curative effect should be properly judged from patient's symptoms, laboratory test indicators, survival rate and other aspects after artificial liver therapy.

Effect of artificial liver with double plasma molecular absorb system model on patients' platelets and corresponding treatment strategy / 北京大学学报(医学版)

OBJECTIVE@#To compare the effects of artificial liver treatment with double plasma molecular adsorption system(DPMAS) mode and traditional plasma exchange (PE) mode on platelets in patients, and to evaluate the clinical efficacy of recombinent human thrombopoietin (rhTPO) in the treatment of thrombocytopenia.@*METHODS@#A total of fifteen patients undergoing artificial liver with DPMAS model admitted to the Fifth Affiliated Hospital of Guangzhou Medical University from January 2018 to November 2020 were selected and included in the DPMAS group, and another 15 patients receiving PE were selected and included in the PE group. The improvement of clinical symptoms, such as fatigue, jaundice, oliguria, edema, etc. before and after artificial liver treatment was compared between the two groups, and the trend of blood routine (especially platelet), coagulation function and other indexes before and after treatment were compared between the two groups. The use of rhTPO and the number of platelets were recorded during treatment.@*RESULTS@#The improvement rate of clinical symptoms in DPMAS group was 86.67%, which was higher than that in PE group, but the difference was not statistically significant (P>0.05). There was no statistical significance in the outcome of the two groups within 90 days (P>0.05). There was no significant difference in white blood cell (WBC) and hemoglobin (HB) between the two groups after treatment (P>0.05). However, the level of platelet(PLT) in DPMAS group was significantly lower than that before treatment (P < 0.05), and was significantly lower than that in PE group (P < 0.05). After treatment, the international normalized ratio (INR) level in PE group was significantly improved (P < 0.05), but there was no significant difference in the INR level in DPMAS group (P>0.05). The patients in the DPMAS group received an average of (8.2±3.1) doses of rhTPO and (1.5±0.3) IU of platelet transfusions during hospitalization. In DMPAS group, platelets increased significantly after infusion of terbium.@*CONCLUSION@#Compared with PE mode, the artificial liver with DPMAS mode can reduce platelet levels in patients, but the application of rhTPO can stimulate platelet regeneration and increase platelet levels in the patients, thereby reducing the risk of bleeding due to platelet hypoplasia.

Prospects for the ex situ liver machine perfusion in Brazil / Perspectivas para a máquina de perfusão hepática ex situ no Brasil

ABSTRACT Brazil, like most countries in the world, experiences the expansion of extended criteria donors, mainly due to the aging of the population and the obesity epidemic. Concerns regarding the quality of these organs along with the vast territorial areas of the country compromise the utilization rate of livers from donors and aggravate the discrepancy between the number of liver transplants performed and the needed. Ex situ liver machine perfusion offers superior preservation for livers from extended criteria donors, limiting cold ischaemia time and offering the possibility of evaluation of their function before transplantation as well as the reconditioning of marginal organs. Objections such as the financial cost, difficulty in transporting the device between hospitals, and demand of trained professionals in the handling of the device must be pondered with the possibility of increasing the number of transplants and the utilisation rate of donor organs. The optimal use of this resource, through the careful selection of donors and the appropriate technical and scientific knowledge, can ensure an effective and successful implementation of this technology.

RESUMO O Brasil, como a grande parte dos países no mundo, convive com a expansão de doadores de órgãos de critério estendido, principalmente devido ao envelhecimento da população e à epidemia de obesidade. Dúvidas em relação à qualidade desses órgãos juntamente com as longas extensões territoriais do país comprometem a taxa de utilização de fígados de doadores e agravam a discrepância entre o número de transplantes hepáticos realizados e o necessário. A máquina de perfusão hepática oxigenada ex situ oferece preservação superior para fígados de doadores de critério estendido, limitando o tempo de isquemia fria e oferecendo a possibilidade de avaliação da função antes do transplante bem como o recondicionamento de órgãos de qualidade limítrofe. Objeções como o custo financeiro, dificuldade de transporte do dispositivo entre hospitais e a demanda de profissionais treinados para o manuseio devem ser apreciadas diante da possibilidade do aumento do número de transplantes e a maior taxa de utilização de órgãos de doadores. A otimização na utilização desse recurso, por meio da seleção cuidadosa de doadores, e o conhecimento técnico-científico adequado podem garantir a implementação eficaz e bem sucedida dessa tecnologia.

Guideline for diagnosis and treatment of liver failure / 中华肝脏病杂志

Liver failure is a familiar clinical severe liver disease syndrome with a very high mortality rate. Over the years, scholars from around the world have been exploring the definition, etiology, classification, types, diagnosis and treatment, and prognostic judgment of liver failure. Reflecting changes, that have transpired in recent years at home and abroad relevant to clinical evidence, this guideline updates the information previously published by the Chinese Society of Infectious Diseases, Chinese Medical Association, Liver Failure and Artificial Liver Group, Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Guidelines for Diagnosis and Treatment of Liver Failure (2012 Edition).

Three-dimensional (3D) printing of mouse primary hepatocytes to generate 3D hepatic structure

PURPOSE: The major problem in producing artificial livers is that primary hepatocytes cannot be cultured for many days. Recently, 3-dimensional (3D) printing technology draws attention and this technology regarded as a useful tool for current cell biology. By using the 3D bio-printing, these problems can be resolved. METHODS: To generate 3D bio-printed structures (25 mm × 25 mm), cells-alginate constructs were fabricated by 3D bio-printing system. Mouse primary hepatocytes were isolated from the livers of 6–8 weeks old mice by a 2-step collagenase method. Samples of 4 × 10⁷ hepatocytes with 80%–90% viability were printed with 3% alginate solution, and cultured with well-defined culture medium for primary hepatocytes. To confirm functional ability of hepatocytes cultured on 3D alginate scaffold, we conducted quantitative real-time polymerase chain reaction and immunofluorescence with hepatic marker genes. RESULTS: Isolated primary hepatocytes were printed with alginate. The 3D printed hepatocytes remained alive for 14 days. Gene expression levels of Albumin, HNF-4α and Foxa3 were gradually increased in the 3D structures. Immunofluorescence analysis showed that the primary hepatocytes produced hepatic-specific proteins over the same period of time. CONCLUSION: Our research indicates that 3D bio-printing technique can be used for long-term culture of primary hepatocytes. It can therefore be used for drug screening and as a potential method of producing artificial livers.

Effect of shift rotation culture on formation and activity of encapsulated hepatocytes aggregates / 浙江大学学报·医学版

To observe the effect of uniform and shift rotation culture on the formation and activity of the alginate-chitosan (AC) microencapsulated HepLL immortalized human hepatocytes and HepG2 cells aggregates.AC microcapsulated HepG2 and HepLL cells were randomly divided into two groups. Each group was divided into 3 subgroups according to uniform and shift rotation culture.The size and number of aggregates were observed and measured under laser confocal microscopy and inverted microscope dynamically. The amount of albumin synthesis was detected by ELISA, the clearance of ammonia was detected by colorimetry, and diazepam conversion function was detected by high performance liquid chromatography (HPLC).On day 6, 8, 10, 12, 14 and 16, the number and size of the aggregates, albumin synthesis, diazepam clearance and ammonium clearance increased significantly in shift rotation culture group than in uniform group (all<0.01). The albumin synthesis, diazepam clearance, and ammonium clearance in the microencapsulated HepLL groups were significantly higher than those of HepG2 cells at any time (all<0.01).Shift rotation culture can significantly promote the formation and increase the activity of AC microencapsulated HepLL and HepG2 aggregates, and HepLL cells may be more suitable for bioartificial liver than HepG2.

Successful salvage treatment of acute graft-versus-host disease after liver transplantation by withdrawal of immunosuppression: a case report

Acute graft-versus-host disease (GVHD) following liver transplantation is a rare but fatal complication. The correct diagnosis and management of GVHD after liver transplantation are still major challenges. Herein, we reported successful salvage treatment of acute GVHD by withdrawal of immunosuppression in a patient who presented with fever, skin rashes, and decreased blood cell counts after liver transplantation. This case highlights the need for awareness of drug-induced liver injury if liver function tests are elevated during treatment, especially in patients taking multiple potentially hepatotoxic drugs, such as broad-spectrum antibiotics. When occurs, an artificial liver support system is a useful tool to provide temporary support of liver function for the patient in the event of drug-induced liver injury.

Predictive value of pediatrics end-stage liver disease or model for end-stage liver disease score in the prognosis of pediatric acute liver failure treated with artificial liver support system / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the predictive value of pediatrics end-stage liver disease (PELD) or the model for end-stage liver disease (MELD) in the prognosis of pediatric acute liver failure (PALF) treated with artificial liver support system (ALSS).</p><p><b>METHOD</b>The clinical data of 47 children with acute liver failure seen from August 2008 to July 2013 treated in Children's Hospital, Fudan University were analyzed. Thirty children were treated with ALSS in addition to conventional comprehensive medical treatment (ALSS group). Seventeen children were treated with only conventional comprehensive medical treatment (control group). The main biochemical parameters and coagulation function parameters before and after treatment were compared in the ALSS group and the mortality rates were compared between the two groups. The patients were graded by PELD or MELD when they were hospitalized and the relationship of PELD or MELD scores and mortalities of child patients with the receiver operating characteristic curve (ROC) were analyzed.</p><p><b>RESULT</b>There were significant differences in total bilirubin (TB) ((302 ± 208) vs. (161 ± 129) µmol/L); alanine aminotransferase (ALT) ((161 ± 225) vs. (761 ± 834) U/L); aspartate aminotransferase ( AST) (66 (35, 123 ) vs. 447 (184, 1,129 ) U/L) ; international normalized ratio (INR) ((2.6 ± 1.6) vs. (5.1 ± 4.0)); prothrombin time activity percentage (PTA) ((42 ± 25)% vs. (22 ± 13)%); albumin( ALB) ((35 ± 5) vs. (33 ± 6) g/L) in the ALSS group after treatment. Through the ROC curve analysis, the best PELD/MELD threshold was 25 to predict the patients survival after ALSS therapy, with a sensitivity of 92. 3% , and a specificity of 94.1% at the cutoff point. The area under the ROC curve was 0. 912. The mortality of patients with PELD or MELD score below 25 in the ALSS group (1/13) was lower than the control group (3/4) (P = 0.022), and the mortality of patients with PELD or MELD score over 25 (16/17) was higher than that of the control group (10/13) (P = 0.290).</p><p><b>CONCLUSION</b>PELD or MELD score is a valid index in prognostic evaluation of ALSS therapy, which may provide an evidence for the therapeutic strategies of PALF. Patients with PELD or MELD score below 25 treated with ALSS obtained more benefit.</p>

Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells.

Hepatocyte Isolation, Culture, and Its Clinical Applications / 한양의대학술지

Hepatocytes, parenchymal cells of the liver, are specially differentiated cells to perform most of the body metabolisms. Many clinicians are interested in utilizing hepatocytes as cell therapeutics. A great number of investigators have been harvesting hepatocytes using two-step portal vein perfusion method, in which Ca2+-free EDTA-containing buffer and Ca2+-enriched collagenase solution are pumped into liver in sequence. Among various attempts for long-term culture of hepatocytes, collagen gel sandwich configuration is recognized to be the most effective technique. In the biomedical field, hepatocytes have been used in three methods of applications. First is hepatocyte transplantation for the treatment of acute, chronic liver failure and metabolic diseases. Donated livers not suitable for organ transplantation are rare, which is the major human hepatocyte source. This shortage of human hepatocyte source is expected to be resolved by virtue of rapid progressing stem cell technologies. The second application is biological components of bioartificial liver (BAL) system for acute liver failure patients. Due to the lack of functional activity of clinically studied BAL systems and difficulty of establishing a manufacturing system for ready-to-use, additional research activities are stagnated. The third utilization of hepatocytes is in vitro drug screening studies such as drug metabolism, transport, biliary excretion, and toxicity tests. If cell therapeutic treatments using hepatocytes are clinically valuable to some types of liver diseases, the demand for liver transplantation would be significantly diminished.

Sistemas de soporte hepático extracorpóreo: [revisión] / Extracorporeal liver support systems: [review]

Introducción. Los sistemas de soporte hepático extracorpóreo (SHE) surgen como una alternativa al trasplante hepático (TH), dado el incremento en la incidencia de falla hepática aguda (FHA), falla hepática crónica agudizada (FHCA), así como las restricciones en la oferta de órganos. Objetivo. Revisión de la literatura de los sistemas de soporte hepático extracorporeo. Metodología. Búsqueda de la literatura publicada entre julio de 1990 y noviembre de 2010 en las principales bases de datos médicas que incluyeron MEDLINE, SciELO y EMBASE, de artículos que analizaran tecnologías relacionadas con sistemas de soporte hepático en cuanto a sus especificaciones técnicas, sus usos y la evidencia respecto a su efectividad en pacientes con algún tipo de falla hepática que requirieran soporte.Resultados. Estos sistemas pueden dividirse en artificiales (hemofiltración, sistema MARS) y bioartificiales (como el Hepatassist™). Su fundamento consiste en reemplazar los procesos de destoxificación relacionados específicamente con el sistema de bilirrubinas, la eliminación de aminoácidos aromáticos, agentes inflamatorios y el manejo de los productos de degradación del sistema de la coagulación. Los recientes avances en bioingeniería y biogenética han hecho que estas tecnologías se acerquen cada vez más a una forma ideal, permitiendo que sean utilizados con relativo éxito en humanos. Los SHE, en su gran mayoría en desarrollo, pretenden no solo actuar como puente al TH, sino que, en casos puntuales, pueden llegar a ser la piedra angular del tratamiento mientras la FHA logra resolverse.

Background. Extracorporeal liver support systems (ELS) have emerged as an alternative to liver transplant (LT), given the growing incidence of acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and the limited organ supply. Objective. Review of literature about Extracorporeal Liver Support Systems. Methodology. A literature search was conducted on the main medical databases including MEDLINE, SciELO and EMBASE for papers published between July 1990 and November 2010 looking at technologies associated with liver support systems, their technical specifications, their use, and evidence regarding their effectiveness in patients with some forms of liver failure requiring support. Results. These systems may be divided into artificial (hemofiltration, MARS) and bioartificial (such as the Hepatassist™). They work by replacing detoxification processes associated specifically with bilirubins, aromatic aminoacids, and inflammatory agents, and the elimination of breakdown products of coagulation. Recent advances in bioengineering and biogenetics have brought these technologies closer to hetheideal, enabling their use in humans with a relative degree of success. ELS systems, most of them still under development, are designed not only to act as a bridge for LT but may also become the cornerstone of treatment in specific cases while the ALF resolves.

New evidence of porcine endogenous retrovirus transmission with new bio-artificial liver system: a experimental study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the potential transmissibility of porcine endogenous retrovirus (PERV) from a newly-developed porcine hepatocyte bioartificial liver (BAL) system prior to human clinical trial by using a live canine model.</p><p><b>METHODS</b>Five normal beagles were treated with the new BAL support system for six hours. Samples of plasma from the BAL system and whole blood from the beagles were collected at regular intervals over the six month study period. DNA and RNA were isolated from both the peripheral blood mononuclear cells (PBMCs) and plasma for evaluation by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR, respectively, to detect PERV and the Sus scrofa cytochrome B normalization standard. In addition, RT activity and the in vitro infectivity of the plasma were detected in HEK293 cells.</p><p><b>RESULTS</b>All five beagles remained in stable physical health throughout the treatment and survived until the end of the study. PERV RNA-positivity and RT activity were only detected in the plasma samples from the 3rd BAL treatment cycle. All other samples, including PBMCs and plasma, were negative for PERV RNA, PERV DNA, and RT activity. In addition, none of the sera samples showed in vitro infectivity.</p><p><b>CONCLUSION</b>Application of our BAL system does not lead to PERV transmission.</p>

Impact of heparin on coagulation index during the therapy of molecular adsorbent recirculating system in patients with liver failure / 中南大学学报(医学版)

OBJECTIVE@#To investigate the impact of coagulative parameters on different anticoagulation systems in molecular adsorbent recirculating system (MARS) in subjects with liver failure, and to evaluate the safety of different anticoagulation methods .@*METHODS@#A prospective experimental observation was designed. According to anticoagulation Methods , 174 MARS treatment sessions for 146 patients with liver failure and prothrombin time activity percentage (PTA) ≤ 40% were randomly divided into 2 groups: 92 MARS treatment sessions in the heparin-free group and 82 in the low-dose heparin group. Time points of 0, 0.5, 1, 2, 3, 4, 5 and 6 h were selected to observe the coagulation changes of prothrombin time (PT), PTA, thrombin time (TT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) dynamically. Adverse events such as line / filter coagulation, rupture and bleeding were also investigated and compared due to frequency and severity between the 2 groups.@*RESULTS@#There was no difference in PT, PTA, INR between the 2 groups, but significant differences were observed in APTT and TT and fibrinogen (Fbg). APTT and TT levels in the low-dose heparin group was increased rapidly after the first given dose of anticoagulant heparin and reached the peak within 30 min.The levels at each time point was statistically different between the 2 groups (P<0.05). A significant difference in the Fbg level was obtained between the 2 groups. In the low-dose heparin group it was stabilized and increased slightly at the end of the treatment. While in the heparin-free group it was decreased gradually and reached a ravine at the end of the treatment. A curve was observed after 2.5 h treatment between the 2 groups (P=0.001). There were 2 cases of severe bleeding after MARS was finished in the heparin group, and 1 was terminated because of degree III clotting in the heparin-free group.@*CONCLUSION@#Fibrinogen should be adsorbed while the blood touches the MARS circuit path and anticoagulants can prevent it. Comprehensive analysis of blood platelet count (BPC), fibrin degradation products (FDP), D-dimer and clinical symptoms is critical and required to determine the coagulation status to select an anticoagulation system before MARS. The use of low dose heparin in MARS improves the disorder of hypercoagulable state during the high coaguation period, while heparin-free during low coagulation period can effectively prevent the occurrence of bleeding and improve the mechanism of blood coagulation by reducing heparin-like substance in the blood.

Effects of non-bioartificial liver support system on Gc-globulin in patients with liver failure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure.</p><p><b>METHODS</b>81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment. The correlation between Gc globulin and IL-10, IL-4, IL-18, TNFa, endotoxin, NO, sVCAM-1and sICAM-1were analyzed by Pearson correlation analysis.</p><p><b>RESULTS</b>The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P less than 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P less than 0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFa, SVCAM-1, SICAM-1 and NO. In contrast, no correlation existed between Gc globulin and IL-10. The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.</p>

Clinical study on hybrid bioartificial liver supporting system for acute on chronic liver failure patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To construct an hybrid bioartificial liver supporting system, and observe its effectiveness and safety on patients with acute on chronic liver failure.</p><p><b>METHODS</b>Hybrid bioartificial liver supporting system (HBALSS) was constructed using bioreactor with HepG2 cells transfected with human augmenter of liver regeneration (hALR) gene. 12 acute on chronic liver failure patients were divided into 2 groups randomly. The treatment group was treated with the hybrid bioartificial liver support system. The group underwent plasma exchange was used as control.</p><p><b>RESULTS</b>In the treatment group, four patients recovered, one patient died of hepatic encephalopathy, one patient died of hepatorenal syndrome, one patient recovered, but died of gastrointestnal bleeding after 1 year. In control group, two patients recovered, one patient underwent orthotropic liver transplantation, and three patients died of liver failure.</p><p><b>CONCLUSION</b>The hybrid bioartificial liver supporting system with HepG2 cell line was established successfully and have certain safety and effectiveness on acute on chronic liver failure patients.</p>

Artificial Liver Devices and Bioartificial Liver Systems: Current Status / 대한이식학회지

Acute liver failure is a rapidly progressive disease of the liver associated with high morbidity and mortality without liver transplantation. Although good survival after transplantation can be achieved, due to the disparity between patients awaiting transplantation and available organs, many patients die due to progression of the disease while waiting for a liver graft. To reduce the high morbidity and mortality associated with acute liver failure, attempts have been made during the last several decades to develop a temporary liver support system, such as artificial and bioartificial livers. The artificial liver is a non-biological device mainly aimed at the removal of accumulated toxins during liver failure, and the bioartificial liver is a biological device that has bioreactors containing living hepatocytes which provide both biotransformation and synthetic liver functions. There are currently 3 artificial livers available in the market that have been actively used in the clinical field, and 11 bioartificial livers that have been developed and have undergone clinical trials. In this article, we will discuss about the 3 artificial liver devices and 5 bioartificial liver systems that are the most advanced and have been widely evaluated clinically. Also, the characteristics and the preclinical data of the first bioartificial liver system developed in Korea that is currently under clinical investigation, will be discussed.

The efficacy research of multi-layer flat-plate bioartificial liver on acute liver failure / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of newly developed multi-layer flat-plate bioartificial liver in treatment of canines with acute liver failure.</p><p><b>METHODS</b>Porcine hepatocytes and bone marrow mesenchymal stem cells were cocultured in newly developed multi-layer flat-plate bioreactor. Acute liver failure in canine models was induced by D-galactosamine administration.Sixteen canine models were divided into two groups: treatment group (n = 8) and control group (n = 8). Biochemical parameters were determined for 7 days after treatment and liver specimens were collected for histological analysis.</p><p><b>RESULTS</b>Hepatic encephalopathy and general conditions were significantly improved in the treatment group, but no changes in the control group. Alanine aminotransferase was significantly decreased from (1512 ± 183) U/L to (86 ± 25) U/L in the treatment group, aspartate aminotransferase was significantly decreased from (1472 ± 365) U/L to (46 ± 11) U/L, lactate dehydrogenase was significantly decreased from (463 ± 76) U/L to (312 ± 84) U/L, total bilirubin was significantly decreased from (28.8 ± 6.2) µmol/L to (12.5 ± 3.6) µmol/L, ammonia was significantly decreased from (56 ± 15) µmol/L to (34 ± 10) µmol/L, and prothrombin time were significantly decreased in the treatment group but increased in the control group, albumin was improved in the treatment group but decreased in the control group. There were 5 canines survived in the treatment group but only 3 in the control group. But there was no difference on survival rates between the two group (P = 0.294).</p><p><b>CONCLUSION</b>The application of newly developed multi-layer flat-plate bioartificial liver system was effective in the treatment of canines with acute liver failure.</p>

Construction and experimental study on off-line hybrid bioartificial liver supporting system with human liver cell line / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To construct an off-line hybrid bioartificial liver supporting system with human liver cell line, and study it's effect on the plasma from patients with liver failure.</p><p><b>METHODS</b>We established the bioreactor using Psu-2s (Fresenius) cultured with Hep G2 cell transfected with human augmenter of liver regeneration (hALR) gene, then constructed a hybrid bioartificial liver supporting system, at last using the bioartificial liver support system to purify the plasma treated 2 hours with serum bilirubin absorbent, separated from acute on chronic liver failure patients infected by hepatitis B virus.</p><p><b>RESULTS</b>Bioreactor was successful constructed. The cell viability in perigastrum of bioreactor is 85.2% and cell propagated rapidly. Before and after treating with bilirubin absorbent, serum total bilirubin was (176.19 +/- 54.14) micromol/L and (50.1 +/- 16.85) micromol/L respectively (P = 0.0002). While there were no significance difference in the level of albumin, urea and glucose. At the begin and end of treatment with bioartificial liver, serum total bilirubin was (50.10 +/- 16.85) micromol/L and (30.27 +/- 15.02) micromol/L respectively (P = 0.000), the urea and albumin increased, urea has significantly difference, but the change of albumin hasn't.</p><p><b>CONCLUSION</b>The off-line hybrid bioartificial liver supporting system with human liver cell line were builded successfully and have synthesis and metabolism functions for acute on chronic liver failure patients.</p>

Microgravity culture of hepatocytes on cellulose/gelatin macroporous microcarrier / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare macroporous microcarrier Cytopore 2 and Cultispher S for their effects in microgravity culture of CL-1 cells.</p><p><b>METHODS</b>CL-1 cells were cultured on Cytopore 2 and Cultispher S respectively in a rotational cell culture system (RCCS) in a volume of 50 ml. Dynamic morphological observation and cell counting and functional test were carried out during the cell culture.</p><p><b>RESULTS</b>The cells were capable of adhering to and proliferating on both of the microcarriers, reaching the growth peak on day 9 of cell culture with the maximum cell density of 4x10(6)/ml on cultispher S. Albumin was significantly higher in the supernatant of Cytopore 2 than in that of Cultispher S on days 10, 11, and 12 (P<0.05), and the urea level in the supernatant of cytopore 2 was also significantly higher on days 10 and 11 (P<0.05).</p><p><b>CONCLUSION</b>The cells cultured on Cytopore 2, though with a smaller cell number, display better functions than those cultured on Cultispher S under RCCS conditions.</p>

Artificial and bioartificial liver support systems for acute and acute-on-chronic liver failure: a meta-analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of artificial and bioartificial liver support systems for management of acute and acute-on-chronic liver failure.</p><p><b>METHODS</b>Articles documenting randomized clinical trials concerning any liver support systems vs standard conservative therapy, published between January, 1970 and June, 2008, were retrieved by database searching. Of the 1134 articles retrieved, 12 randomized trials involving 479 patients were included. The data were extracted and the trial quality was assessed by 2 independent reviewers. The primary outcome measure was all-cause mortality, and the results were combined on the risk ratio (RR) scale.</p><p><b>RESULTS</b>Of the 12 trials included, 10 assessed artificial liver support systems for acute or acute-on-chronic liver failure, and 2 assessed bioartificial systems for acute liver failure. Overall, the liver support systems had moderate effect on mortality compared with standard conservative therapy (RR=0.80; 95% CI 0.664-0.969, P=0.022). Meta-regression indicated that the effect of the support systems depended on the type of liver failure (P=0.00). In stratified meta-analyses, the support systems appeared to reduce the mortality by 43% in acute-on-chronic liver failure (RR=0.57; 95% CI 0.39-0.84, P=0.004), but not in acute liver failure (RR=0.899; 95% CI 0.72-1.12, P=0.361).</p><p><b>CONCLUSION</b>Artificial liver support systems reduce the mortality of acute-on-chronic liver failure as compared with standard conservative therapy, but have no significant effect on the mortality of acute liver failure. Bioartificial liver support systems lower the mortality rates in both acute and acute-on-chronic liver failure, and should be the future focus of development.</p>