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

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World Journal of Gastroenterology 2006年第46期12卷 7503-7507页

作者： Yasushi Kawazoe Susumu Eguchi Nozomu Sugiyama Yukio Kamohara Hikaru Fujioka Takashi Kanematsu Department of Transplantation and Digestive Surgery Nagasaki University Graduate School of Biomedical Sciences 1-7-1 Sakamoto Nagasaki 852-8501 Japan

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.

关键词： Bioartificial liver artificial liver Continuous hemodiafiltration Hepatocytes Acute liver failure,Continuous plasma exchange

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

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World Journal of Gastroenterology 2006年第31期12卷 5055-5059页

作者： Jin-Zhong Yuan Qi-Fa Ye Ling-Ling Zhao Ying-Zi Ming Hong Sun Shai-Hong Zhu Zu-Fa Huang Min-Min Wang Blood Purification Center Xiangya Transplantation Institute Third Xiangya Hospital of Central South University Changsha 410013 Hunan Province China

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.

关键词： liver transplantation artificial liver Sequential Organ Failure Assessment Risk factors analysis

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基于压印细胞片组装的仿生肝小叶

Science Bulletin 2024年第10期69卷 1448-1457页

作者：王经琳黄丹青陈涵旭赵远锦 Department of Hepatobiliary Surgery Hepatobiliary InstituteNanjing Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210008China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

liver-tissue engineering has proven valuable in treating liver diseases,but the construction of liver tissues with high fidelity remains ***,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 *** achieve this,the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics *** 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 *** 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 *** 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 *** believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.

关键词： Biomimetic Hepatic lobules Cell sheets 3D imprinting Tissue engineering artificial liver

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

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World Journal of Gastroenterology 2017年第11期23卷 1974-1979页

作者： Ryoichi Sakiyama Brandon J Blau Toshio Miki Department of Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033United States

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.

关键词： artificial liver Clinical trial Hepatocytes Pluripotent stem cells Bioreactors

Molecular adsorbent recycling system in treat-ing patients with acute liver failure: a bridge to liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2004年第4期3卷 508-510页

作者： Yi-Tao Ding, Qing-Xiang Xu, Yu-Dong Qiu and Yi-Jun Yang Nanjing, China Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Medical College of Nanjing University Hepatobiliary In- stitute of Nanjing University Hepatobiliary Surgery Institute of Nanjing, Nanjing 210000, China Department of Hepatobiliary Surgery Affiliated Drum Tower Hospital of Medical College of Nanjing University Hepatobiliary Institute of Nanjing University Hepatobiliary Surgery Institute of Nanjing Nanjing 210000 China. dingyitao@***

BACKGROUND:Acute liver failure is still a life-threaten- ing disease although it can be treated by liver transplanta- tion. This study was conducted to assess the molecular ad- sorbent recycling system (MARS), which may bridge acute liver failure patients to liver transplantation. METHODS: Biochemical indexes and other clinical data were analyzed of 8 patients with acute liver failure, who had been treated by MARS for 34 times and subsequent Piggyback liver transplantation. RESULTS: After treatment with MARS, the levels of tran- saminase and total bilirubin decreased markedly, but coagu- lation function remained unimproved. All patients survived and discharged from the hospital. CONCLUSION: MARS is effective in bridging patients with acute liver failure to liver transplantation.

关键词： molecular adsorbent recycling system liver transplantation acute liver failure artificial liver

Isolation and primary culture of rat hepatocytes

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Hepatobiliary & Pancreatic Diseases International 2002年第1期1卷 77-79页

作者： Xiao-Li Liu Lan-Juan Li Zhi Chen From the Department of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Department of Infectious Diseases First Affiliated Hospital Zhejiang University of Medicine Hangzhou 310003 China

Objective: To find out an optimal condition for isola-tion and primary culture of ***: Rat hepatocytes were isolated by a two-stepcollagenase perfusion, and cultured in hepatozyme-SFM. The reduction of MTT to formazan salt was ex-amined. Supernatant medium was collected for analy-sis of alanine aminotransferase（ALT） and ***: The two-step collagenase perfusion yielded39±12×10;cells/g liver tissue with a viability of88%±2%. Fine morphology and stable urea synthesisfor one week could be achieved when hepatocytes werecultured in ***: High yield of hepatocytes can be isolatedwith two-step collagenese perfusion. Hepatozyme-SFM is suitable for sustained growth of hepatocytes.

关键词： hepatocytes isolation primary culture artificial liver

liver support therapy with molecular adsorbents recirculating system in liver failure： a summary of 252 cases from 14 centers in China

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Chinese Medical Journal 2008年第21期121卷 2197-2201页

作者： WANG Min-min CHEN Shi-jun YE Qi-fa YANG Yi-jun CHEN Shi-bin ZHOU Xin-min GUO Li-min ZHANG Yue-xin DING Xiao-qiang HU Xiao-bin LUO Hong-tao LIU Yi-he WANG Wen-ya Therapeutic Blood Purification Research Center University of Rostock Germany Department of artificial liver Therapy Jinan Infectious Diseases Hospital Jinan Shandong 250021 China Xiangya Transplantation Medical Academy Central South University Changsha Hunan 410013 China Department of artificial liver Therapy Nanjing Second People's Hospital Southeast University Medical College Nanjing Jiangsu 210003 China Division of Infectious Diseases First Affiliated Hospital of Jiangxi Medical College Nanchang Jiangxi 330006 China Institute of Digestive Diseases Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 400038 China ICU & artificial liver Support Center Beijing Ditan Hospital Beijing 100011 China Institute of Hepatology First Hospital Xinjiang Medical University Urmqi Xinjiang 830000 China Department of Nephrology Fudan University Zhongshan Hospital Shanghai 200032 China Department of artificial liver Therapy Guangzhou No. 8 Hospital Guangzhou Guangdong 510060 China ITU & Blood Purification Center First People's Hospital of Foshan Foshan Guangdong 528000 China Tianjin First Central Hospital Tianjin Organ Transplantation Institute Tianjing 300192 China Department of Infectious Diseases West China Hospital Sichuan University Chengdu Sichuan 610041 China

Background A liver support therapy, named molecular adsorbents recirculating system （MARS）, has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus （HBV） based liver failure. Methods This report analyzed data of 252 patients （mean age （44.9±12.7） years） in three groups： acute severe hepatitis （ASH）, subacute severe hepatitis （SSH） and chronic severe hepatitis （CSH）. The largest group was CSH （156 patients, 61.9%）, and 188 patients （74.6%, 188/252） were infected with HBV. Results MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity （PTA） and median arterial pressure （MAP）. There was a decrease in hepatic encephalopathy （HE） grade and Child-Turcotte-Pugh （CTP） scale. Thirty-nine of 188 HBV patients （20.7%） dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant （65/151,43%）, whereas the early and middle stage patients had a better prognosis： early stage survival, including orthotopic liver transplantation （OLT） survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. Conclusions MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic re

关键词： liver failure artificial liver Hepatitis B

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

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World Journal of Emergency Medicine 2014年第3期5卷 214-217页

作者： Mao-qin Li Jun-xiang Ti Yun-hang Zhu Zai-xiang Shi Ji-yuan Xu Bo Lu Jia-qiong Li Xiao-meng Wang Yan-jun Xu Department of Intensive Care Xuzhou Central HospitalAffiliated to School of MedicineSoutheast University

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 ***:Signifi cant improvement was observed in HR,MAP,PaO2/FiO2,total bilirubin(TBIL) and alanine aminotransferase(ALT) levels after treatment(Pliver 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.

关键词： Severe acute liver failure artificial liver Plasma exchange Hemoperfusion Continuous veno-venous hemodiafi ltration

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

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Journal of Hainan Medical University 2022年第16期28卷 26-29页

作者： LI Chu‑yi WANG Jun-ke LI Bin WEN Xue WEI Xiao-jing YU Xiao-hui Department of Gastroenterology 940 Hospital of Joint Service of PLAGansu Lanzhou 730050China Ningxia Medical University Ningxia Yinchuan 750004China

Objective:To study and evaluate the clini1cal effect of plasma exchange in the adjuvant treatment of chronic and acute liver ***:Totally 60 patients with chronic and acute liver failure in our department were divided into two *** control group received comprehensive treatment and the plasma exchange group received plasma *** 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 ***: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(Pliver 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.

关键词： artificial liver Chronic and acute liver failure Impact assessment