Challenge In Liver Transplantation Research Articles

Taxifolin attenuates hepatic ischemia-reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy

BackgroundHepatic ischemia-reperfusion (I/R) injury stands as a recurring clinical challenge in liver transplantation, leading to mitochondrial dysfunction and cellular imbalance. Mitochondria, crucial for hepatocyte metabolism, are significantly damaged during hepatic I/R and the extent of mitochondrial damage correlates with hepatocyte injury. PINK1/Parkin-mediated mitophagy, is a specialized form of cellular autophagy, that maintains mitochondrial quality by identifying and removing damaged mitochondria, thereby restoring cellular homeostasis. Taxifolin (TAX), a natural flavonoid, possesses antioxidant, anti-inflammatory and anticancer properties. This study aimed at investigating the effects of TAX on hepatic I/R and the underlying mechanisms. MethodsC57BL/6 mice were pretreated with TAX or vehicle control, followed by 60 min of 70% hepatic ischemia. After 6 h of reperfusion, the mice were euthanized. In vitro, TAX-pretreated primary hepatocytes were subjected to oxygen glucose deprivation/reperfusion (OGD/R). ResultsHepatic I/R caused mitochondrial damage and apoptosis in hepatocytes, but TAX pretreatment mitigated these effects by normalizing mitochondrial membrane potential and inhibiting reducing apoptotic protein expression. TAX exerted its protective effects by enhancing mitophagy via the PINK1/Parkin pathway. Moreover, silencing the PINK1 gene in primary hepatocytes reversed the beneficial effects of TAX. ConclusionThe results of the study demonstrate that promoting mitophagy through the PINK1/Parkin pathway restores mitochondrial function and protects the liver from I/R, suggesting that it may have therapeutic potential for the treatment of hepatic I/R.

Impact of Paired Remote Ischemic Preconditioning on Postreperfusion Syndrome in Living-Donor Liver Transplantation: A Propensity-Score Matching Analysis.

Background and Objectives: Postreperfusion syndrome (PRS) is a significant challenge in liver transplantation (LT), leading to severe circulatory and metabolic complications. Ischemic preconditioning (IPC), including remote IPC (RIPC), can mitigate ischemia-reperfusion injury, although its efficacy in LT remains unclear. This study evaluated the impact of paired RIPC, involving the application of RIPC to both the recipient and the living donor, on the incidence of PRS and the need for rescue epinephrine during living-donor LT (LDLT). Materials and Methods: This retrospective observational cohort analysis included 676 adult patients who had undergone elective LDLT between September 2012 and September 2022. After applying exclusion criteria and propensity score matching (PSM), 664 patients were categorized into the paired RIPC and non-RIPC groups. The primary outcomes were the occurrence of PRS and the need for rescue epinephrine during reperfusion. Results: The incidence of PRS and the need for rescue epinephrine were significantly lower in the paired RIPC group than in the non-RIPC group. Furthermore, the incidence of postoperative acute kidney injury was lower in the paired RIPC group. Multivariable logistic regression adjusted for propensity scores indicated that paired RIPC was significantly associated with a reduced occurrence of PRS (odds ratio: 0.672, 95% confidence interval: 0.479-0.953, p = 0.021). Conclusions: Paired RIPC, involving both the recipient and the living donor, effectively reduces the occurrence of PRS and the need for rescue epinephrine during LDLT. These findings suggest that paired RIPC protects against ischemia-reperfusion injury in LDLT. Future randomized controlled trials are needed to verify our results and to explore the underlying mechanisms of the protective effects of RIPC.

Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives.

Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

Challenges in Liver Transplantation for Hepatocellular Carcinoma: A Review of Current Controversies.

Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients' comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT.

Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury

Background and aimHepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methodsThis study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. ResultsSerum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. ConclusionsElevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

LIVER TRANSPLANTATION IN LIVER CIRRHOSIS DUE TO HEPATITIS C: A CRITICAL ANALYSIS OF ITS ADVANTAGES, CHALLENGES AND IMPACT ON PATIENTS' QUALITY OF LIFE.

Liver cirrhosis caused by hepatitis C is a serious condition that often leads to the need for liver transplantation for patients in advanced stages of the disease. This procedure has been a crucial measure to improve survival and quality of life for these patients. However, its effectiveness and impact are the subject of critical analysis due to the associated challenges, such as the scarcity of donor organs, the risks of postoperative complications and the possibility of recurrence of hepatitis C virus infection in the new liver. Understanding the advantages and challenges of liver transplantation in hepatitis C liver cirrhosis is essential to optimize patient outcomes and quality of life. Objective: To critically analyze the advantages, challenges and impact on the quality of life of patients undergoing liver transplantation due to liver cirrhosis caused by hepatitis C. Methodology: A systematic literature review was carried out following the PRISMA guidelines. The PubMed, Scielo and Web of Science databases were searched for articles published in the last 10 years. The descriptors used were "liver transplant", "liver cirrhosis", "hepatitis C", "advantages", "challenges" and "quality of life". The inclusion criteria were original studies that addressed the topic in humans, written in English, Portuguese or Spanish. Exclusion criteria were animal studies, literature reviews and studies focusing on liver conditions other than hepatitis C. Results: The results highlighted the effectiveness of liver transplantation in improving the survival and quality of life of patients with liver cirrhosis due to hepatitis C. However, challenges persist, including the limited availability of donor organs and the risk of relapse of hepatitis C virus infection. Strategies to mitigate these challenges have been discussed, such as the use of next-generation antiviral therapies. Conclusion: Liver transplantation is a vital intervention for patients with liver cirrhosis caused by hepatitis C, providing significant benefits in terms of survival and quality of life. However, the associated challenges need to be addressed to further improve outcomes and ensure the long-term success of this procedure.

Spliced CEACAM1: A Potential Novel Biomarker and Target for Ameliorating Liver Ischemia-reperfusion Injury.

Hepatic ischemia-reperfusion injury remains a significant challenge in liver transplantation potentially leading to delayed graft function, primary nonfunction, and sometimes rejection. Understanding the underlying mechanisms and implementing mitigation strategies are essential for improving transplant outcomes and patient survival. A recent study published by Dery et al shows that alternative splicing of carcinoembryonic antigen-related cell adhesion molecule 1 regulated by hypoxia inducible factor 1 alpha under stress enhances hepatic ischemia tolerance in mice and humans. The authors identified a direct binding of hypoxia inducible factor 1 alpha to the promoter region of polypyrimidine tract-binding protein 1 splicing enzyme, resulting in carcinoembryonic antigen-related cell adhesion molecule 1-short induction and improved posttransplant outcomes. This study has notably elucidated a potential biomarker pertaining to the quality of liver transplant donor grafts.

Developments and challenges of liver transplantation in China

With the vigorous promotion of organ donation after citizen death in China, increased utilization of marginal livers, and continuous expansion of hepatocellular carcinoma indications for liver transplantation, innovations in techniques such as auxiliary liver transplantation, pediatric liver transplantation laparoscopic liver transplantation, magnetic liver transplantation,and non-ischemic liver transplantation have significantly improved the number of liver transplantation surgery performed, patient survival rates, and graft survival rates in China, while complication rates have gradually decreased. As such,liver transplantation in China has now reached leading or advanced levels internationally. In the new development context,Chinese liver transplantation faces new opportunities and challenges for development. Evolutions in basic diseases of transplant recipients and tumor classifications of will further broaden the population eligible for transplantation and introduce new demands for liver transplantation procedures. Emerging technologies including artificial organs, xenotransplantation,and artificial intelligence are bringing prospects for advancing liver transplantation. Looking ahead, the progression of liver transplantation will go beyond prioritizing patient survival rates and graft survival rates alone, instead emphasizing improved quality of life for transplant recipients post-surgery to an even greater extent.

New Developments and Challenges in Liver Transplantation.

Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment. Thomas E. Starzl performed the first human liver transplant 60 years ago. It has since become an established treatment for end-stage liver disease, both acute and chronic, including metabolic diseases and primary and, at present piloting, secondary liver cancer. Advances in surgical and anaesthetic techniques, refined indications and contra-indications to transplantation, improved donor selection, immunosuppression and prognostic scoring have allowed the outcomes of liver transplantation to improve year on year. However, there are many limitations to liver transplantation. This review describes the milestones that have occurred in the development of liver transplantation, the current limitations and the ongoing research aimed at overcoming these challenges.

Treatment of maple syrup urine disease: Benefits, risks, and challenges of liver transplantation.

Maple syrup urine disease (MSUD) is caused by a deficiency in the activity of the branched-chain α-ketoacid dehydrogenase (BCKD) complex, promoting the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their respective α-keto acids. MSUD is an autosomal recessive hereditary metabolic disorder characterized by ketoacidosis, ataxia, coma, and mental and psychomotor retardation. The mechanisms involved in the brain damage caused by MSUD are not fully understood. Early diagnosis and treatment, as well as proper control of metabolic decompensation crises, are crucial for patients' survival and for a better prognosis. The recommended treatment consists of a high-calorie diet with restricted protein intake and specific formulas containing essential amino acids, except those accumulated in MSUD. This treatment will be maintained throughout life, being adjusted according to the patients' nutritional needs and BCAA concentration. Because dietary treatment may not be sufficient to prevent neurological damage in MSUD patients, other therapeutic strategies have been studied, including liver transplantation. With transplantation, it is possible to obtain an increase of about 10% of the normal BCKD in the body, an amount sufficient to maintain amino acid homeostasis and reduce metabolic decompensation crises. However, the experience related to this practice is very limited when considering the shortage of liver for transplantation and the risks related to the surgical procedure and immunosuppression. Thus, the purpose of this review is to survey the benefits, risks, and challenges of liver transplantation in the treatment of MSUD.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis

Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p= 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p= 0.001). Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

Assessment of the nutritional status of patients before, one, and three months after liver transplantation: A multi-center longitudinal study

Nutrition management is an important pre-operative and post-operative challenge in liver transplantation. Preoperative malnutrition is associated with increased length of intensive care unit (ICU) stay, mortality, and length of hospital stay in liver transplant patients. This study aimed to evaluate the nutritional status of patients before and after liver transplantation and post-transplant complications. This longitudinal study was conducted on liver transplant patients in Montaserieh Hospital, Mashhad and Firoozgar Hospital, Tehran from May 2021 to January 2022. Demographic characteristics, Subjective Global Assessment (SGA) standard questionnaire, anthropometric indices, laboratory analyses, and 3-day food records were collected before, one, and three months after transplantation. Thirty-nine patients with a mean age of 48.4±14.2 were evaluated. Prevalence of severe malnutrition was 43.6% (56.3% women and 34.8% men) before transplantation. Body mass index (BMI), body weight, lean mass, total body water, and total serum protein significantly decreased after transplantation compared to before transplantation (P<0.001). One month after transplantation, 54% of the patients lost more than 10% of their weight. Energy intake increased significantly after transplantation (P<0.001). A significant relationship was observed between BMI (P=0.005) and metabolic complications and between Arm Muscle Circumference and renal complications (P=0.003) after transplantation. A cut-off point of 4.6 was determined for the phase angle in terms of SGA three months after transplantation. Malnutrition, weight loss, and nutritional problems were common in liver transplantation patients. Screening for nutritional status is necessary in these patients to treat or prevent malnutrition-related complications.

Challenges in liver transplantation in the context of a major pandemic.

Coronavirus disease-2019 (COVID-19) has led to a temporary suspension of liver transplant activity across the world and the remodeling of care for patients on the waiting list and transplant recipients with the increasing use of remote consultations. Emerging evidence shows that patients with more advanced liver disease are at increased risk of severe COVID-19 and death, whereas transplant recipients have similar risk with the general population which is mainly driven by age and metabolic comorbidities. Tacrolimus immunosuppression might have a protective role in the post-transplant population. Vaccines that have become rapidly available seem to be safe in liver patients, but the antibody response in transplant patients is likely suboptimal. Most transplant centers were gradually able to resume activity soon after the onset of the pandemic and after modifying their pathways to optimize safety for patients and workforce. Preliminary evidence regarding utilizing grafts from positive donors and/or transplanting recently recovered or infected recipients under certain circumstances is encou raging and may allow offering life-saving transplant to patients at the greatest need. This review summarizes the currently available data on liver trans plantation in the context of a major pandemic and discusses areas of uncertainty and future challenges. Lessons learnt from the COVID-19 pandemic might provide invaluable guidance for future pandemics.

Donation after Circulatory Death Liver Transplantation in Paediatric Recipients

Waiting list mortality together, with limited availability of organs, are one of the major challenges in liver transplantation (LT). Especially in the paediatric population, another limiting factor is the scarcity of transplantable liver grafts due to additional concerns regarding graft size matching. In adults, donation after circulatory death (DCD) liver grafts have been used to expand the donor pool with satisfactory results. Although several studies suggest that DCD livers could also be used in paediatric recipients with good outcomes, their utilisation in children is still limited to a small number of reports. Novel organ perfusion strategies could be used to improve organ quality and help to increase the number of DCD grafts utilised for children. With the current manuscript, we present the available literature of LT using DCD grafts in paediatric recipients, discussing current challenges with the use of these livers in children and how machine perfusion technologies could be of impact in the future.

Long term outcomes and complications of reno-portal anastomosis in liver transplantation: results from a propensity score-based outcome analysis.

Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate post-transplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Between January 2005 and December 2017, 1270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity score (PS)-matched patients without thrombosis (control group), using a 1:3 matching model. The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; P=0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (P=0.133 and P=0.166, respectively). RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

Challenges in liver transplantation for common variable immunodeficiency-related liver disease: a case series and systematic review

BackgroundCommon variable immunodeficiency (CVID) is a rare primary B-cell immunodeficiency disorder associated with multisystem complications of impaired humoral immunity. CVID is characterized by impaired adaptive responses to pathogen challenge and a paradoxical predisposition to a wide range of autoimmune and neoplastic complications. MethodsWe present a case series describing our experience of liver transplantation in two patients with CVID and perform a comprehensive literature review of post-transplant complications and survival outcomes detailing the global experience of 30 reported cases of adult liver transplantation for common variable immunodeficiency-related liver disease (CVIDrLD). ResultsLiver transplantation in CVIDrLD is frequently complicated by atypical infections, autoimmune complications and graft recurrence and is associated with suboptimal long term survival outcomes post-transplantation in comparison to established listing indications for liver transplantation; this is further compounded (median survival 3 vs. 5 years) when removing patients with concomitant chronic hepatitis C infection from the survival analysis. ConclusionsLiver transplantation is associated with poor overall survival outcomes and careful consideration should be given to the phenotype and severity of immunodeficiency, the presence of chronic pathogen colonisation and the extrahepatic burden of disease at the time of assessment. At present, despite careful patient selection, survival post-transplant outcomes fall below acceptable listing thresholds, necessitating a conservative approach to consideration of single organ listing in this context with current available treatments. Patients with a secondary aetiological factor for liver disease may perform better post-transplant.

Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway

BackgroundHepatic ischemia-reperfusion (I/R) injury (IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. MethodsSham or warm hepatic I/R operated mice were pretreated with fisetin (5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation (H/R) model using RAW264.7 macrophages pretreated with fisetin (2.5, 5 or 10 µmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1β (IL-1β), IL-18 and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Protein levels of p-GSK3β, p-AMPK and NLR family pyrin domain-containing 3 (NLRP3)-associated proteins were detected by Western blotting. ResultsCompared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1β, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins (NLRP3, cleaved caspase-1, IL-1β and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1β, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3β and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3β/AMPK signaling. The anti-inflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. ConclusionsFisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3β/AMPK/NLRP3 inflammasome pathway.

An unusual case of median arcuate ligament syndrome with inferior mesenteric artery supply to supra-mesocolic organs: A challenge in liver transplantation

An unusual case of median arcuate ligament syndrome with inferior mesenteric artery supply to supra-mesocolic organs: A challenge in liver transplantation

Changing Trends in Liver Transplantation: Challenges and Solutions.

Despite improvements in postliver transplant outcomes through refinements in perioperative management and surgical techniques, several changing trends in liver transplantation have presented challenges. Mortality on the waitlist remains high. In the United States, Europe, and the United Kingdom, there is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis-related cirrhosis and cancer indications. Meanwhile, donor suitability has decreased, as donors are often older and have more comorbidities. Despite a mismatch between organ need and availability, many organs are discarded. Notwithstanding this, many solutions have been developed to overcome these challenges. Innovative techniques in allograft preservation, viability assessment, and reconditioning have allowed the use of suboptimal organs with adequate results. Refinements in surgical procedures, including live donor liver transplantations, have increased the organ pool and are decreasing the time and mortality on the waitlist. Despite many challenges, a similar number of solutions and prospects are on the horizon. This review seeks to explore the changing trends and challenges in liver transplantation and highlight possible solutions and future directions.

Protein S for Portal Vein Thrombosis in Cirrhotic Patients Waiting for Liver Transplantation.

Portal vein thrombus (PVT) is a challenge in liver transplantation. How PVT develops in cirrhotic patients who already have coagulopathy is unclear. This study aimed to investigate possible contributing factors to PVT in cirrhotic patients. A total of 349 cirrhotic patients who waited liver transplantation were included in this study and 48 of them had PVT. For all the patients, the mean age was 53.5 ± 9.0 year old, and 75.9% of the patients were male. There were 233 (66.8%) patients who had either hepatitis B or C. The mean Model For End-Stage Liver Disease (MELD) score was 16.4 ± 7.5. Eighteen of 48 patients with PVT and 145 of 301 patients without PVT received liver transplantation. Multivariate analysis showed that low protein S level (hazard ratio = 2.46, p = 0.017) was the only independent risk factor for PVT development. Protein S deficiency also demonstrated prognostic value on short-term survival, not only for cirrhotic patients awaiting liver transplantation (69.9% versus 84.1% at 1 year survival, p = 0.012), but also for the patients having liver transplantation (70.4% versus 84.8% at 1 year survival, p = 0.047). In conclusion, protein S level was an independent risk factor for PVT development in decompensated cirrhotic patients, and protein S deficiency was also a prognostic factor for the patients waiting for liver transplantation.