Search Results (56)

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article

Background: Patient survival after liver transplantation is lower in donor–recipient race mismatched patients for indications other than primary sclerosing cholangitis. Objectives: To determine if survival is lower after liver transplantation in donor–recipient race mismatched recipients with primary sclerosing cholangitis. Methods: The Organ Procurement and Transplantation Network database was analyzed for deceased donor adult liver transplant recipients with primary sclerosing cholangitis. Graft and patient survival by donor–recipient race were estimated using Kaplan–Meier survival method and compared using the log-rank test. Multivariable analysis was performed using Cox regression. Results: From 2002 to 2018, 5-year patient survival in White (n = 2223) and Black recipients (n = 491), was 89.8% and 87.1%, respectively. Five-year patient survival for the donor–recipient pairs, White–White (n = 1622), Black–Black (n = 110), Black–White (n = 335), and White–Black (n = 314) was 90.8%, 91.1%, 87.1%, and 86.0%, respectively, p = 0.026. In multivariable analysis, 5-year patient mortality was higher in Black recipients of White donors [HR 1.69, 95% CI 1.16, 2.45], compared to White recipients of White donors. Conclusions: Five-year patient mortality after deceased donor liver transplantation for primary sclerosing cholangitis is higher in Black recipients who received livers from White donors compared to matched White donors and recipients. Full article

This study aimed to compare the contents of copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe) in healthy liver tissue from deceased liver donors (DGs), in cirrhotic tissue from patients without (CIR) or with hepatocellular carcinoma (CIR-HCC) and in HCC tissue from the latter patients. Liver tissue samples were obtained from cirrhotic liver transplant recipients, with (n = 14) and without HCC (n = 14), and from DGs (n = 18). In patients with HCC, both cirrhotic and tumor tissue was collected. The tissue metal content was measured using atomic absorption spectrometry. The Cu content of DG tissue was significantly lower than that of CIR-HCC and HCC tissue but not CIR tissue. The tissue Zn and Mg contents were significantly higher in DG tissue than in CIR, CIR-HCC, and HCC tissues. No difference was observed for Fe. The Cu/Zn ratio progressively increased in DG, CIR, CIR-HCC, and HCC tissues. The increased Cu content in cirrhotic and tumor tissue of HCC patients and the fact that the latter had the highest value for the Cu/Zn ratio indirectly suggest the potential role of these metals in hepatocarcinogenesis. These findings support a pathophysiological basis for further experimental studies to investigate the potential therapeutic implications of pharmacological agents targeting metal homeostasis in this malignancy. Full article

Background: Living donor liver transplantation (LDLT) has become a widely accepted alternative to deceased donor liver transplantation (DDLT). Nevertheless, the available meta-analyses shed light on a perplexing issue regarding which transplant is better. Therefore, we performed an umbrella review to summarize and evaluate the evidence from current meta-analyses. Methods: Two independent reviewers conducted a search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 1 June 2024. The methodological quality of each included meta-analysis was evaluated using AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). Results: The search identified 10 meta-analyses from 486 individual articles, including cohort studies and observational studies. Regrettably, the quality of these meta-analyses ranged from critically low to moderate. Receipt of LDLT offers a survival advantage to the patients with HCC compared with DDLT but with a higher complication rate. However, high-quality studies are required in the future to validate our assertions owing to the low certainty of the evidence. Conclusions: Despite the complication risks, LDLT remains a cost-effective option without compromising patient and graft survival, especially for HCC patients. Extensive, well-designed studies are essential to validate these conclusions. Full article

Background/Objectives: Liver transplantation is a life-saving procedure for patients with end-stage liver disease. In recent years, the demand for liver transplantation has surpassed the supply of available donor organs. Utilizing extended-criteria donors (ECDs) alleviates the scarcity of suitable donor livers for transplantation. One of the ECD was donors with a history of alcohol abuse. Liver grafts from donors with a history of chronic and active alcohol abuse are typically promptly excluded, diminishing the available organ pool. This highlights the need to re-evaluate the donor exclusion criteria and expand the organ pool to address the ongoing shortage. Methods: We examined adult (>18 years) liver transplant recipients who received deceased donor livers and had a documented history of alcohol abuse between 2011 and 2024. Liver transplant indications were conventional and included hepatitis C virus (HCV), non-alcoholic steatohepatitis, alcoholic liver disease, alcoholic liver disease coexisting with HCV, cryptogenic cirrhosis, chronic cholestatic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, metabolic liver disease, hepatocellular carcinoma, and alcoholic hepatitis. We compared the 1-year, 5-year, and 9-year survival rates with those of liver recipients from non-alcohol-consuming donors. Results: In total, 370 liver recipients from deceased donors with a documented history of alcohol abuse were included. At 1 year post-transplant, survival was comparable between the two groups. Conclusions: Liver transplantation from deceased donors with a history of alcohol abuse yielded survival rates and liver function outcomes comparable to those from non-alcohol-using donors. By expanding the criteria to include carefully screened alcohol-using donors, transplant programs can improve access to life-saving transplantations. Full article

Background: Living donor liver transplantation (LDLT) is the predominant transplantation technique in regions with low rates of deceased donation. Right-lobe grafting is adopted in most clinical and radiological donor/recipient scenarios. Due to the considerable variations in right-lobe hepatic venous anatomy, many techniques have been used over the years for the purpose of appropriate venous outflow reconstruction during the recipient procedure. In this paper, we present the technical details and consequences of a complex venous outflow reconstruction model (CORM) based on experience, and the long-term patency results obtained using the model. Methods: Data of patients with end-stage liver disease who underwent LDLT between 21 December 2017 and 29 November 2022 were prospectively collected and retrospectively reviewed. The nomenclature of CORM was assigned when three or more hepatic vein anastomoses were performed. Patients with CORM (CORM group; n = 69) were compared with non-CORM patients (non-CORM group; n = 130) in terms of demographic, pre- and postoperative clinical, and follow-up features. Results: Sixty-nine recipients had three or more separate outflow reconstructions (RHV, RIHV, and one or more anterior sectoral veins); these constituted the CORM group. The estimated graft volume of the CORM group was significantly lower than that of the non-CORM group (833 vs. 898; p = 0.022), and the mean GRWR was also significantly lower (1.1 vs. 1.2; p = 0.004). CORM cases showed longer anhepatic phases, as well as longer times for cold and warm ischemia, than non-CORM cases (63 vs. 51 min, 46 vs. 38 min, and 48 vs. 33 min, p < 0.001), though no difference was found with respect to total operative duration. There were no statistical differences between the two groups with respect to rates of in-hospital re-exploration, length of ICU stay, or length of total hospital stay. Graft survival rates at 1 year, 3 years, and 5 years were 88.1%, 83.3%, and 83.3%, respectively, in the CORM group, and 82.9%, 80.2%, and 70.6%, respectively, in the non-CORM group (p = 0.167). Conclusions: Performing three or more CORMs in right-lobe LDLT is not associated with inferior outcomes, either with regard to perioperative variables or to patient and graft outcomes. Right-lobe graft with complex venous anatomy from a living donor should not be a determinant factor for donor exclusion. Full article

Background: Anastomotic biliary strictures (BSs) are among the most common complications after liver transplantation (LT), accounting for 5–15% of adult recipients after deceased-donor transplantation. For some reason, this percentage increased in our center in recent years, and the goal of this study was to find out the reasons behind this to avoid this complication in the future. Material and Methods: We retrospectively analyzed the occurrence of anastomotic biliary strictures in 230 cadaveric-donor LTs performed in our center between January 2019 and December 2023. Many variables related to the donor, recipient, and surgical procedure were compared between patients who experienced BS and those without this complication. Statistical analysis was performed using Fisher’s exact test, a one-way ANOVA test, and Pearson’s correlation coefficient. Results: Altogether, 51 patients (22.17%) developed BSs. This percentage was especially high in 2023 (32%). The only significant differences found in study group compared to the control group were the requirement of additional doses of vasopressors during surgery (45 (86.53%) vs. 138 (77.09%), p = 0.0001) and more frequent instances of reperfusion syndrome (8/51 (15.68%) vs. 11/179 (6.11%), p = 0.00001). Conclusions: We conclude that ischemia during LT has an advantage over technical parameters in the development of BSs after LT. Appropriate blood volume resuscitation as opposed to inotropic treatment may reduce the risk of this complication. Full article

Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain—such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease—technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation. Full article

Combined liver–kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli’s disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients. Full article

Background/Objectives: Liver retransplantation (reLT) is the only option for pediatric patients experiencing graft loss. Despite recent advancements in surgical techniques and perioperative management, it remains a high-risk procedure. Our aim is to describe our experience in pediatric reLT, focusing on the technical aspects and surgical challenges. Methods: We systematically analyzed surgical reports from pediatric reLT performed at our center between 2006 and 2023 to identify recurrent intraoperative findings and specific surgical techniques. We focused on challenges encountered during different phases of reLT, including hepatectomy, vascular, and biliary reconstruction. Additionally, we compared patient and graft survival rates among different groups. Results: During the study period, 23 children underwent 25 reLT procedures at our center. Major surgical challenges included complex hepatectomy and vascular reconstructions, necessitating tailored approaches. Our analysis shows that patient and graft survival were significantly lower for reLT compared to primary transplantation (p = 0.002). Early reLT had a significantly lower graft survival compared to late reLT (p = 0.002), although patient survival was comparable (p = 0.278). Patient and graft survival rates were comparable between the first and second reLT (p = 0.300, p = 0.597). Patient survival tended to be higher after living-donor liver transplantation (LDLT) compared to deceased-donor liver transplantation (DDLT), although the difference was not statistically significant (p = 0.511). Conclusions: Pediatric reLT involves significant technical challenges and lower survival rates. Advances in perioperative management are crucial for improving outcomes. Further research is needed to optimize surgical strategies and evaluate the long-term benefits of LDLT in pediatric reLT. Full article

Background: Induction therapy with depleting antibodies in the setting of liver transplantation (LT) is discussed controversially to this day. The rabbit antithymocyteglobulin (ATG) Thymoglobulin (rATG) was introduced as early as 1984 and was frequently used as a standard regime for induction therapy after LT. There are no public reports characterizing Grafalon (ATG-F), a novel ATG, as an induction agent after LT. Objectives: The aim of this observational non-interventional study was to investigate the safety and efficacy of Grafalon induction therapy and characterize its clinical effects in the setting of LT. Methods: A cohort of 80 patients undergoing deceased donor LT at the Medical University of Vienna and receiving Grafalon as part of the clinical standard immunosuppressive regimen was prospectively included between March 2021 and November 2022. Patients were monitored closely for leukocytopenia and thrombocytopenia during the first postoperative week and followed up for incidence and severity of biopsy-proven acute rejection (BPAR), overall survival, and bacterial infections in the first year after LT. Results: The incidences of thrombocytopenia and leukocytopenia following Grafalon treatment peaked on postoperative day four, with 64% and 31%, respectively. However, there were no cases of severe leukocytopenia after the first postoperative week. Induction therapy with Grafalon resulted in a rate of localized bacterial infections and bacteremia of 28% and 21%, respectively. The rate of BPAR was 12.5% in the first year after LT; the one-year survival rate in this cohort was 90%. Conclusions: Overall, this study provides evidence of the safety and efficacy of Grafalon as an induction agent. Further studies investigating the potential long-term effects of Grafalon, as well as comparison studies with different immunosuppressive regimens, are needed in order to draw further conclusions. Full article

Obesity is a well-documented risk factor for the development of hepatocellular carcinoma (HCC) in the general population. The applicability of these findings to liver recipients is uncertain, and the results of available data have not been unanimous. The objective of the current study was to investigate the impact of the pre-operative body mass index (BMI) on oncological outcomes of liver transplantation due to HCC. Methods: This observational retrospective study enrolled all patients with histologically confirmed HCC who underwent liver transplantation from a deceased donor in our centre between 2008 and 2018. Results: Overall, 83 patients were enrolled and were subsequently stratified according to their pre-operative BMI into three groups: patients with normal body weight (n = 53), patients with overweight (n = 23), patients with obesity (n = 7). Overall tumour recurrence was 12%. BMI failed to predict the 5-year recurrence-free survival (p = 0.55), risk of tumour recurrence (p = 0.314) and overall 5-year survival (p = 0.19) in liver recipients. Conclusions: BMI was proven to be an unreliable surrogate measure of obesity for predicting oncological outcomes among liver recipients. Other obesity indices should be referenced to assess cancer-related prognosis more accurately in these groups of patients. Full article

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612–7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290–1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT. Full article

The utilization of COVID-19-positive donors has expanded the donor pool for transplantation since the initiation of COVID allograft utilization protocols. However, the biopsy-proven PCR transmission rate of COVID-19 from these allografts has not been well documented. In August 2021, an institutional COVID-19-positive allograft protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA, and post-operative day 7 nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) swabs were collected. The primary endpoints evaluated included COVID-19 RNA on biopsy and COVID-19 detected via nasopharyngeal RT-PCR swab on post-operative day 7. A total of 20 vaccinated recipients underwent transplantation (17 liver only, 3 simultaneous liver and kidney) with whole liver allografts from 20 COVID-19-positive deceased donors between August 2021 and April 2022. 95% (19/20) of donors were asymptomatic at the time of donation. On post-reperfusion liver allograft biopsies, COVID-19 RNA was found in 10% (2/20) of the samples. All the recipients were COVID-19-negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. The use of COVID-19 allografts appears to be a safe practice, with no PCR-detectable transmission of COVID-19 despite 10% of the liver allografts having COVID-19 RNA present on post-reperfusion biopsy. Full article