Demand For Liver Transplantation Research Articles

The Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers.

The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP. The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival. The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P = 0.235, respectively). The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.

Obesity management for the pre–liver transplant and post–liver transplant patient

Obesity management for the pre–liver transplant and post–liver transplant patient

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia.

The demand for liver transplantation in the Kingdom of Saudi Arabia (KSA) is associated with the country’s high burden of liver disease. Trends in the epidemiology of liver transplantation indications among recipients in KSA have changed over 20 years. Non-alcoholic steatohepatitis has eclipsed the hepatitis C virus in the country due to the effective treatment strategies for HCV. Risk factors for NASH, like type 2 diabetes mellitus, obesity, and hyperlipidemia, are becoming a major concern and a leading indication for liver transplantation in the KSA. There is also a significantly increased prevalence and incidence of genetic adult familial liver diseases in KSA. New immunosuppressive agents and preservation solutions, improved surgical capabilities, and early disease recognition and management have increased the success rate of liver transplant outcome but concerns about the side effects of immunosuppressive therapy can jeopardise long-term survival outcomes. Despite this, indications for liver transplantation continue to increase, resulting in ongoing challenges to maximize the number of potential donors and reduce patient mortality rate while expecting to get transplanted. The Saudi Center of Organ Transplant is the recognized National Organ Donation Agency for transplantation, which renders important support for procurement and allocation of organs. This guidance document aims to help healthcare providers in managing patients in the liver transplant setting.

Temporal Trends in Utilization and Outcomes of DCD Livers in the United States.

Historically, donation after circulatory death (DCD) livers were frequently discarded because of higher mortality and graft loss after liver transplantation (LT). However, the demand for LT continues to outstrip the supply of "acceptable" organs. Additionally, changes in the donor pool, organ allocation, and clinical management of donors and recipients, and improved clinical protocols might have altered post-DCD-LT outcomes. We studied 5975 recovered DCD livers using US Scientific Registry of Transplant Recipients data from 2005 to 2017, with a comparison group of 78 235 adult donation after brain death (DBD) livers recovered during the same time period. We quantified temporal trends in discard using adjusted multilevel logistic regression and temporal trends in post-LT mortality and graft loss for DCD LT recipients using adjusted Cox regression. DCD livers were more likely to be discarded than DBD livers across the entire study period, and the relative likelihood of discard increased over time (adjusted odds ratio [aOR] of discard DCD versus DBD 3.854.455.14 2005-2007, 5.225.876.59 2015-2017) despite improving outcomes after DCD LT. Mortality risk for DCD LTs decreased in each time period (compared with 2005-2007, aHR 2008-2011 0.720.840.97, aHR 2012-2014 0.480.580.70, aHR 2015-2017 0.340.430.55), as did risk of graft loss (compared with 2005-2007, aHR 2008-2011 0.690.810.94, aHR 2012-2014 0.450.550.67, aHR 2015-2017 0.360.450.56). Despite dramatic improvements in outcomes of DCD LT recipients, DCD livers remain substantially more likely to be discarded than DBD livers, and this discrepancy has actually increased over time. DCD livers are underutilized and have the potential to expand the donor pool.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Liver graft harbouring hydatid disease: how far can we extend our donor pool?

As the current demand for liver transplantation exceeds our donor pool, the donor search is shifted towards the extended donor criteria. The livers harbouring hydatid disease are a controversial source of grafts. We report the use of a liver graft harbouring hydatid disease in urgent liver transplantation in a patient with autoimmune hepatitis. Corroborated with previous experiences, we show that the liver grafts harbouring hydatid cysts provide a rare but valuable source of organs.

Liver transplantation and aging.

An increase in the average life expectancy, paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation (LT) among the elderly. Some of the most common indications for LT including hepatocellular carcinoma, alcohol-related liver disease, chronic hepatitis C and non-alcoholic fatty liver disease tend to affect older patients. Transplant professionals are faced with an increasing demand for LT among elderly patients in an age of organ shortage and it is important that risk and benefits are carefully weighed in order to achieve the optimum use of precious liver grafts.

ESTABLISHMENT OF LIVER TRANSPLANTATION IN THE UNITED ARAB EMIRATES FROM DECEASED AND LIVING DONORS

Liver transplantation (LT) in the Middle East remains confined to a few countries and relies heavily on the availability of living donors. In many countries in the region, definition of brain death remains unclear, impeding the establishment of deceased donor organ transplantation. Since the first deceased donor liver transplant (DDLT) in the region in 1990, growth of DDLT has been slow, accounting for less than 20% of all LT as of 2013. This report summarizes the formal establishment of LT in the UAE from living and deceased donors. The passage of the brain death law in May 2017 enabled the formal establishment of deceased organ donation in the UAE. This landmark law enabled the transplant community in the UAE to establish a network of donor hospitals to identify potential donors who met criteria for brain death. Efforts to bring this to fruition involved close collaboration of key stakeholders, including Cleveland Clinic Abu Dhabi (CCAD), Ministry of Health and Prevention, Department of Health in Abu Dhabi, Dubai Health Authority, UAE national transplant committee, Cleveland Clinic Foundation, Mubadala Healthcare and the Abu Dhabi health services company. This collaborative effort enabled the successful establishment of a multi-organ transplant center at CCAD and initiation of LT from deceased donors within 9 months of the laws’ passage. The first multi-organ procurement and transplant from a brain dead donor in the UAE occurred on July 15, 2017. The first deceased donor LT in the UAE was performed on Feb 1, 2018 as part of a multi-organ procurement and transplant process. We have since performed an additional ten LT from deceased donors, of which 7 recipients have completed a year of follow-up post-transplant. An extensive collaborative effort with our colleagues at Cleveland Clinic’s main campus in Cleveland, Ohio resulted in the first successful Living donor LT (LDLT) in the UAE on July 29, 2018. We have since performed an additional 14 LDLTs (overall: four right lobe and 10 left lobe grafts), with seven LDLT recipients having completed a year of follow-up post-transplant. Figure 2 highlights key milestones in LT in the UAE and figure 3 illustrates activity since inception of LT at CCAD, highlighting the challenges related to deceased donor organ availability and underscoring the role of LDLT in meeting the growing demand for LT in the country.In conclusion, we report the successful establishment of LT in the UAE, from both deceased and living donors. LDLT has enabled us to meet clinical demand, while efforts to improve deceased donor organ donation bear fruit. Continued growth and success of transplantation in the UAE is contingent upon increasing awareness of organ donation. Ongoing initiatives include creation of a national digital organ donor registry, inclusion of consent for donation in the Emirates national ID card, regional organ sharing agreements for critically ill patients and establishment of donation after circulatory death.

Using Artificial Intelligence for Predicting Survival of Individual Grafts in Liver Transplantation: A Systematic Review.

The demand for liver transplantation far outstrips the supply of deceased donor organs, and so, listing and allocation decisions aim to maximize utility. Most existing methods for predicting transplant outcomes use basic methods, such as regression modeling, but newer artificial intelligence (AI) techniques have the potential to improve predictive accuracy. The aim was to perform a systematic review of studies predicting graft outcomes following deceased donor liver transplantation using AI techniques and to compare these findings to linear regression and standard predictive modeling: donor risk index (DRI), Model for End-Stage Liver Disease (MELD), and Survival Outcome Following Liver Transplantation (SOFT). After reviewing available article databases, a total of 52 articles were reviewed for inclusion. Of these articles, 9 met the inclusion criteria, which reported outcomes from 18,771 liver transplants. Artificial neural networks (ANNs) were the most commonly used methodology, being reported in 7 studies. Only 2 studies directly compared machine learning (ML) techniques to liver scoring modalities (i.e., DRI, SOFT, and balance of risk [BAR]). Both studies showed better prediction of individual organ survival with the optimal ANN model, reporting an area under the receiver operating characteristic curve (AUROC) 0.82 compared with BAR (0.62) and SOFT (0.57), and the other ANN model gave an AUC ROC of 0.84 compared with a DRI (0.68) and SOFT (0.64). AI techniques can provide high accuracy in predicting graft survival based on donors and recipient variables. When compared with the standard techniques, AI methods are dynamic and are able to be trained and validated within every population. However, the high accuracy of AI may come at a cost of losing explainability (to patients and clinicians) on how the technology works.

Mesenchymal Stromal Cells, a New Player in Reducing Complications From Liver Transplantation?

In response to the global burden of liver disease there has been a commensurate increase in the demand for liver transplantation. However, due to a paucity of donor organs many centers have moved toward the routine use of marginal allografts, which can be associated with a greater risk of complications and poorer clinical outcomes. Mesenchymal stromal cells (MSC) are a multi-potent progenitor cell population that have been utilized to modulate aberrant immune responses in acute and chronic inflammatory conditions. MSC exert an immunomodulatory effect on innate and adaptive immune systems through the release of both paracrine soluble factors and extracellular vesicles. Through these routes MSC can switch the regulatory function of the immune system through effects on macrophages and T regulatory cells enabling a switch of phenotype from injury to restoration. A key benefit seems to be their ability to tailor their response to the inflammatory environment without compromising the host ability to fight infection. With over 200 clinical trials registered to examine MSC therapy in liver disease and an increasing number of trials of MSC therapy in solid organ transplant recipients, there is increasing consideration for their use in liver transplantation. In this review we critically appraise the potential role of MSC therapy in the context of liver transplantation, including their ability to modulate reperfusion injury, their role in the reduction of medium term complications in the biliary tree and their potential to enhance tolerance in transplanted organs.

The NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (ASH) are advanced forms of fatty liver diseases that are associated with a high morbidity and mortality worldwide. Patients with ASH or NASH are more susceptible to the progression of fibrosis and cirrhosis up to the development of hepatocellular carcinoma. Currently, there are limited medical therapies available. Accompanied by the asymptomatic disease progression, the demand for liver transplants is high. This review provides an overview about the growing evidence for a central role of NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex that acts as a central driver of inflammation via activation of caspase 1, maturation and release of pro-inflammatory cytokines including interleukin-1β, and trigger of inflammatory pyroptotic cell death in both NASH and ASH. We also discuss potential therapeutic approaches targeting NLRP3 inflammasome and related upstream and downstream pathways to develop prognostic biomarkers and medical treatments for both liver diseases.

Expanding the donor pool: Hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation.

Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.

Predictors of demand for liver transplantation in children undergoing Kasai portoenterostomy for biliary atresia

Context Biliary atresia (BA) remains the most common indication for pediatric liver transplantation worldwide. Ultimately, 50–80% of BA patients will require a liver transplant Thus, much of the research in the field has focused on identifying predictors for transplant and optimizing the efficacy of Kasai portoenterostomy (KPE), in order to decrease the need for transplantation and avoid the risks of lifelong immunosuppression. Aim The aim of this study was to identify perioperative risk factors for the need of liver transplantation following KPE operation for BA. Patients and methods A retrospective analysis of 150 patients undergoing KPE for BA at Hepatobiliary and Pancreatic Surgery Department, National Liver Institute, Menoufia University, from May 2013 to May 2018, was carried out. Patients were divided into two groups: group one included 73 (48.7%) patients who survived without the need for liver transplantation and group two included 77 (51.3%) patients with mortality, listed for liver transplantation or transplanted; thereafter, logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Statistical analysis used Continuous variables were expressed as mean±SD and categorical variables as proportions. Univariate analysis for the two groups were carried out using the independent samples t test for continuous variables and χ2 test for categorical variables. Logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Receiver operating characteristic analysis was used for the cut-off determination of predictive parameters using MedCalc application, version 18.2.1. Results The mean age at the time of operation was 74.9±14.6 days after birth (range, 31–111 days); there were 70 (46.7%) male babies and 80 (53.3%) female babies. The mean preoperative weight was 4.6±0.6 kg, while the mean preoperative height was 57.3±3.58 cm. Total bilirubin and albumin levels at 1 and 3 months following KPE were associated with death or the need for liver transplantation; however, only a total bilirubin level of more than 6 mg/dl at 3 months is an independent predictor of the need for liver transplantation. Age at the time of KPE and postoperative steroid use were not associated with improved transplant-free survival. Conclusion Total bilirubin level of more than 7.3 mg/dl at 1 month and a level of more than 6 mg/dl at 3 months after KPE are predictive of the need for liver transplantation (P

Update on Liver Transplantation: What is New Recently?

ABSTRACTLiver transplantation (LT) is an evolving area of medicine for the treatment of certain types of malignancies and acute and chronic liver failures. Since the topic is evolving, new literature is increasingly available. In recent years, with the emerging potent antiviral therapies, hepatitis C virus-infected patients have successful patient and graft survival outcomes. Even human immunodeficiency virus (HIV) positive patients previously contraindicated for organ transplantation are transplanted with comparable outcomes. With increasing demand for LT, the shortage of the donor pool became the rate limiting factor in this hopeful treatment. To overcome waitlist mortality and expand the donor pool, scoring systems have been modified and organs from HIV and/or hepatitis C infected donors are now accepted, under certain circumstances. The new literature also questions the 6-month alcohol abstinence rule for the transplantation of alcoholic liver disease (ALD), in light of early transplantation results from severe alcoholic hepatitis (SAH) trials.How to cite this article: Tasdogan BE, Akosman S, et al. Update on Liver Transplantation: What is New Recently? Euroasian J Hepatogastroenterol 2019;9(1):34-39.

Donor liver quality after hypovolemic shock and venous systemic oxygen persufflation in an experimental animal model

BackgroundThe ever growing demand for liver transplantation inevitably necessitates an expansion of the donor pool. Utilization of “shock organs” is considered suboptimal to date while the associated outcome has hardly been investigated.Materials and methodsMale Wistar rats underwent a period of 30 min of hypovolemic shock. After 24 h livers were explanted and prior to reperfusion underwent either 18 h of cold storage (CS; N = 6) or 17 h of CS followed by 60 min venous systemic oxygen persufflation (VSOP; N = 6). The outcome of “shock organs (SHBD)” was compared to heart-beating donor (HBD; N = 12) as positive control and non-heart-beating donor (NHBD; N = 12) as negative control animal groups. Liver function was assessed by measuring enzyme release (AST, ALT, LDH), bile production, portal vein pressure and hepatic oxygen uptake during reperfusion. For reperfusion, the isolated perfused rat liver system was used.ResultsLiver function was severely limited in NHBD group compared to HBD organs after 18 h of CS (e.g., AST; HBD: 32.25 ± 7.25 U/l vs. NHBD: 790 ± 414.56 U/l; p < 0.005). VSOP improved liver function of NHBD organs significantly (AST; NHBD + VSOP: 333.6 ± 149.1 U/l; p < 0.005). SHBD organs showed a comparable outcome to HBD and clearly better results than NHBD organs after 18 h of CS (AST; SHBD: 76.4 ± 21.9 U/l). After 17 h of CS accompanied by 60 min VSOP, no improvement concerning liver function and integrity of SHBD organs was observed while the results were severely deteriorated by VSOP resulting in higher enzyme release (AST; SHBD + VSOP: 213 ± 61 U/l, p < 0.001), higher portal vein pressure (SHBD: 10.8 ± 1.92 mm Hg vs. SHBD + VSOP: 21.6 ± 8.8 mm Hg; p < 0.05) and lower hepatic oxygen uptake (SHBD: 321.75 ± 3.87 ml/glw/min vs. SHBD + VSOP: 395.8 ± 46.64 ml/glw/min, p < 0.05) at 24 h.ConclusionsOur data suggest that the potential of “shock organs” within liver transplantation may be underestimated. If our findings are reproducable in humans, SHBD grafts should be considered as a valuable source for expanding the thus far limited donor pool.

Projected increase in obesity and non-alcoholic-steatohepatitis-related liver transplantation waitlist additions in the United States.

Nonalcoholic steatohepatitis (NASH) cirrhosis is the fastest growing indication for liver transplantation (LT) in the United States. We aimed to determine the temporal trend behind the rise in obesity and NASH-related additions to the LT waitlist in the United States and make projections for future NASH burden on the LT waitlist. We used data from the Organ Procurement and Transplantation Network database from 2000 to 2014 to obtain the number of NASH-related LT waitlist additions. The obese population in the United States from 2000 to 2014 was estimated using data from the U.S. Census Bureau and the National Health and Nutrition Examination Survey. Based on obesity trends, we established a time lag between obesity prevalence and NASH-related waitlist additions. We used data from the U.S. Census Bureau on population projections from 2016 to 2030 to forecast obesity estimates and NASH-related LT waitlist additions. From 2000 to 2014, the proportion of obese individuals significantly increased 44.9% and the number of NASH-related annual waitlist additions increased from 391 to 1,605. Increase in obesity prevalence was strongly associated with LT waitlist additions 9 years later in derivation and validation cohorts (R2 = 0.9). Based on these data, annual NASH-related waitlist additions are anticipated to increase by 55.4% (1,354-2,104) between 2016 and 2030. There is significant regional variation in obesity rates and in the anticipated increase in NASH-related waitlist additions (P < 0.01). Conclusion: We project a marked increase in demand for LT for NASH given population obesity trends. Continued public health efforts to curb obesity prevalence are needed to reduce the projected future burden of NASH. (Hepatology 2017).

Ronald W. Busuttil, MD, PhD: William P. Longmire, Jr, Chair of Surgery, Chief of Liver and Pancreas Transplantation, Director, UCLA-Dumont Transplant & Liver Cancer Center.

Ronald W. Busuttil, MD, PhD: William P. Longmire, Jr, Chair of Surgery, Chief of Liver and Pancreas Transplantation, Director, UCLA-Dumont Transplant & Liver Cancer Center.

Why we need fairer allocation rules for patients with hepatocellular carcinoma awaiting a liver transplant?

The incidence of both cirrhosis and hepatocellular carcinoma (HCC) is increasing worldwide, despite the current available effective therapy for HCV infection [1]. As liver transplantation is a potential curative option for many patients, the demand for liver transplantation is rising too. Unfortunately, the availability of cadaveric donor livers has remained stable over the years, leading to a widening of the gap between donor organ supply and demand and a higher waiting list mortality or removal rate. The current waiting list mortality and removal rate within Eurotransplant is respectively 18% and 4% [2]. This article is protected by copyright. All rights reserved.

Recent advances in understanding and managing liver transplantation.

Liver transplantation (LT) has been established as the most effective treatment modality for end-stage liver disease over the last few decades. Currently, patient and graft survival after LT are excellent, with 1- and 5-year survival of 90% and 80%, respectively. However, the timing of referral to LT is crucial for improving survival benefit and outcome. The current shortage of donors and the increasing demand for LT currently lengthen the waiting time. Thus, waiting list mortality is about 10–15%, according to the geographical area. For this reason, over the last several years, alternatives to deceased donor LT and new options for prioritizing patients on the waiting list have been proposed.