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Stem cell transplantation for the treatment of end-stage liver disease.

ABSTRACT: The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer, liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety, mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.

SUBMITTER: Wu DB

PROVIDER: S-EPMC6323519 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Stem cell transplantation for the treatment of end-stage liver disease.

Wu Dong-Bo DB Chen En-Qiang EQ Tang Hong H

World journal of hepatology 20181201 12

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer, liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem ce ...[more]

PMID: 30631395

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Project description:End-stage liver disease (ESLD) is characterized by the deterioration of liver function and a subsequent high mortality rate. Studies have investigated the use of adult stem cells to treat ESLD. Here, a systematic review and meta-analysis was conducted to determine the efficacy of a combination therapy with adult stem cell transplantation and traditional medicine for treating ESLD. Four databases-including PubMed, Web of Science, Embase, and Cochrane Library-were investigated for studies published before January 31, 2021. The main outcome indicators were liver function index, model for end-stage liver disease (MELD) scores, and Child‒Turcotte‒Pugh (CTP) scores. Altogether, 1604 articles were retrieved, of which eight met the eligibility criteria; these studies included data for 579 patients with ESLD. Combination of adult stem cell transplantation with conventional medicine significantly improved its efficacy with respect to liver function index, CTP and MELD scores, but this effect gradually decreased over time. Moreover, a single injection of stem cells was more effective than two injections with respect to MELD and CTP scores and total bilirubin (TBIL) and albumin (ALB) levels, with no significant difference in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. With respect to the TBIL levels, patients receiving mononuclear cells (MNCs) experienced a significantly greater therapeutic effect-starting from twenty-four weeks after the treatment-whereas with respect to ALB levels, CD34+ autologous peripheral blood stem cells (CD34+ APBSCs) and MNCs had similar therapeutic effects. Severe complications associated with adult stem cell treatment were not observed. Although the benefits of combination therapy with respect to improving liver function were slightly better than those of the traditional treatment alone, they gradually decreased over time.Systematic review registration: PROSPERO registration number: CRD42021238576.

Project description:BACKGROUND & AIM:The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS:Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ?40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS:Of 65,776 waitlisted patients, 3.3% had MELD ?40 at registration, and an additional 7.3% had MELD scores increase to ?40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ?40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ?50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS:Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.

Project description:INTRODUCTION:During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease. METHODS AND ANALYSIS:This is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with end-stage liver disease. Adult patients (aged 18-75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C-4°C?solution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end-stage liver disease. ETHICS AND DISSEMINATION:The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER:ChiCTR1900021158.

Project description:Despite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation.We performed a retrospective cohort study of transplant-eligible patients with end-stage liver disease using the HealthCore Integrated Research Database (2006-2014; n = 16,824) and Medicaid data from 5 states (2002-2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision-based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database.In an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2-year wait list (95% confidence interval [CI], 25.4%-33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%-12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4%-15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20-2.49). Local organ supply and wait list level demand were not associated with placement on the wait list.In an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference.

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Stem cell transplantation for the treatment of end-stage liver disease.

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Stem cell transplantation for the treatment of end-stage liver disease.

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