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      Artificial Liver Support System Combined with Liver Transplantation in the Treatment of Patients with Acute-on-Chronic Liver Failure

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          Abstract

          Background

          The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF) remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS) combined with liver transplantation (LT) in the treatment of ACLF.

          Methodology/Principal Findings

          One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group) and the other 56 received emergency LT (LT group). The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2–226 days) from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%.

          Conclusions/Significance

          Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.

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          Most cited references22

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          Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review.

          Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation. To evaluate the effect of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. Randomized trials on any support system vs standard medical therapy were included irrespective of publication status or language. Nonrandomized studies were included in explorative analyses. Trials were identified through electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Library, MEDLINE, EMBASE, and the Chinese Medical Database), bibliographies, and contact with experts. Searches were conducted of the entire databases through September 2002. Of 528 references identified, 12 randomized trials with 483 patients were included. Eight nonrandomized studies were included in explorative analyses. Data were extracted and trial quality was assessed independently by 3 reviewers (L.L.K., J.L., B.A-N.). The primary outcome measure was all-cause mortality. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sources of heterogeneity were explored through meta-regression and stratified meta-analyses. Of the 12 trials included, 10 assessed artificial systems for acute or acute-on-chronic liver failure and 2 assessed bioartificial systems for acute liver failure. Overall, support systems had no significant effect on mortality compared with standard medical therapy (RR, 0.86; 95% confidence interval [CI], 0.65-1.12). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P =.03). In stratified meta-analyses, support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR, 0.67; 95% CI, 0.51-0.90), but not in acute liver failure (RR, 0.95; 95% CI, 0.71-1.29). Compared with randomized trials, nonrandomized studies produced significantly larger estimates of intervention effects (P =.01). This review suggests that artificial support systems reduce mortality in acute-on-chronic liver failure compared with standard medical therapy. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure.
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            Liver transplantation: the current situation.

            Over the years, an improving liver transplant (LT) survival rate (1- and 5-year survival of 83% and 75%, respectively) has been instrumental in establishing transplant surgery as a durable therapy for all forms of end-stage liver disease and for some malignant conditions. The success of such treatment has resulted in a progressively increasing demand for liver transplantation. However, at the same time the availability of donor organs has diminished, resulting in the number of potential recipients for liver transplantation exceeding organ supply. Several strategies have been explored with the aim to increase access to liver transplantation, including: obtaining organs from non-heart-beating donors and live donors, and splitting and using livers from expanded donor criteria. This article discusses the utility of the mentioned techniques along with other strategies (e.g., Model for End-Stage Liver Disease [MELD] score), as well as the evolution of indications, contraindications, and postoperative care.
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              Hepatic tissue engineering for adjunct and temporary liver support: critical technologies.

              The severe donor liver shortage, high cost, and complexity of orthotopic liver transplantation have prompted the search for alternative treatment strategies for end-stage liver disease, which would require less donor material, be cheaper, and less invasive. Hepatic tissue engineering encompasses several approaches to develop adjunct internal liver support methods, such as hepatocyte transplantation and implantable hepatocyte-based devices, as well as temporary extracorporeal liver support techniques, such as bioartificial liver assist devices. Many tissue engineered liver support systems have passed the "proof of principle" test in preclinical and clinical studies; however, they have not yet been found sufficiently reliably effective for routine clinical use. In this review we describe, from an engineering perspective, the progress and remaining challenges that must be resolved in order to develop the next generation of implantable and extracorporeal devices for adjunct or temporary liver assist.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                14 March 2013
                : 8
                : 3
                : e58738
                Affiliations
                [1 ]Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
                [2 ]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
                The University of Hong Kong, Hong Kong
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: XX SZ LL. Performed the experiments: XL QL QW. Analyzed the data: ZL XX LZ. Contributed reagents/materials/analysis tools: MZ JW JH JS. Wrote the paper: XX.

                Article
                PONE-D-12-37116
                10.1371/journal.pone.0058738
                3597613
                23516546
                4d16bc3e-e1f6-4d02-9d25-99917162302a
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 November 2012
                : 5 February 2013
                Page count
                Pages: 5
                Funding
                Financial support to the project: this work was supported by the National Science and Technology Major Project (2012ZX10002004), the National High Technology Research and Development Program of China (863 Program 2012AA020204) and the National Basic Research Program of China (973 program 2009CB522404). The funders had no role in study design, data collection and analysis, decision to publish, and preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Surgery
                Transplant Surgery

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