Thrombophilic states in the setting of living donor liver transplantation raises concerns regarding perioperative thromboembolism in the donor, as well as the potential transfer of inherited prothrombotic tendencies through mutated, hepatically synthesised coagulation factors. Screening practices for thrombophilia remain heterogeneous across centers and may result in donor exclusion based on local policies. However, accumulating evidence over the past decade suggests that most prospective donors are asymptomatic, and those with heterozygous inherited thrombophilias-such as Factor V Leiden or Prothrombin G20210A mutation-can safely undergo donation with standard perioperative thromboprophylaxis for recipient and donors. These states are unlikely to be transmitted to the recipient, as extrahepatic synthesis of coagulation proteins contributes to maintaining hemostatic balance. In contrast, donors with a prior history of thromboembolism, high-risk genotypes (e.g., homozygous or compound heterozygous states), or high-risk acquired thrombophilias should generally be excluded owing to an increased risk of thrombotic complications.
Portal hypertension (PH) after liver transplantation (LT) is rare but associated with complications and mortality. The VITRO score-combining von Willebrand factor antigen (vWF-Ag) divided by platelet count (PLT)-reflects PH severity in cirrhosis, yet its prognostic value after LT remains unknown. VITRO score dynamics and clinical outcomes were evaluated in 272 consecutive adult patients with available vWF-Ag measurements undergoing LT between 2016 and 2022 at the Medical University of Vienna. Laboratory parameters were assessed at listing, pre-LT, and at 3-6 and 12 months post-LT. Endpoints included overall mortality and a composite endpoint of PH events and/or liver-related death within 12 months post-LT. At listing, 89% of patients presented with clinically significant portal hypertension (CSPH), with markedly elevated vWF levels (median: 369%, IQR: 262-420) and VITRO scores (median: 3.3, IQR: 2.1-4.8). Following LT, PLT normalized in most cases, with vWF levels decreasing to 206% (IQR: 141-296) and VITRO scores improving to 1.1 (IQR: 0.9-1.5) at 3-6 months post-LT. ΔVITRO was significantly associated with both overall mortality (HR: 1.57, 95% CI: 1.28-1.93, p <0.001) and the composite endpoint of PH events/liver-related death (HR: 1.53, 95% CI: 1.24-1.88, p <0.001) within 12 months post-LT. In multivariable analysis adjusted for albumin, MELD dynamics, and age, ΔVITRO emerged as an independent predictor of mortality (aHR: 1.90, 95% CI: 1.40-2.57, p <0.001), alongside albumin (aHR 0.89, p =0.001) and post-LT MELD decrease (aHR 0.36, p =0.026). These findings remained robust in landmark sensitivity analyses from month 3 post-LT and after bootstrap-based internal validation. Post-LT VITRO score dynamics independently predict liver-related mortality and PH-related complications. Integration of ΔVITRO monitoring into post-LT care may facilitate individualized risk stratification after liver transplantation.
Ascites development in cirrhosis reduces 5-year survival from 80% to 30%, yet substantial heterogeneity exists among patients with comparable ascites severity. This multicenter retrospective cohort study included adult liver transplant candidates with ascites at 4 United States centers (2015-2024). Latent class analysis was performed using 7 clinical variables: ascites grade, bilirubin, albumin, platelet count, estimated glomerular filtration rate, systolic blood pressure, and portal vein thrombosis. The derivation cohort (n=625) from the University of California San Francisco and Columbia University was randomly split 80/20 for model development and internal validation. External validation was performed at the University of Southern California (n=59) and Mayo Clinic (n=93). Primary outcomes were acute kidney injury (AKI) and waitlist mortality over 365 days. Three phenotypes emerged: "CKD-Metabolic" (30.4%, lowest eGFR 76.5 mL/min/1.73 m 2 ), "Vasodilatory-Synthetic Dysfunction" (38.9%, highest bilirubin 7.03 mg/dL, lowest blood pressure 117.5 mmHg), and "PVT-Intermediate" (30.7%, severe thrombocytopenia 68.1×10 3 /μL, 24.0% PVT). In validation cohorts (n=305), phenotypes demonstrated robust classification (mean posterior probability 0.823-0.855). Vasodilatory-Synthetic Dysfunction showed increased AKI risk versus CKD-Metabolic in derivation (MELD 3.0-adjusted HR 2.95, 95% CI 2.07-4.22, p <0.001) and validation cohorts (HR 3.39, 95% CI 1.93-5.94, p <0.001). Competing risk analysis revealed no mortality differences, but Vasodilatory-Synthetic Dysfunction was associated with higher transplantation rates (validation: HR 1.63, 95% CI 1.19-2.22, p =0.002). Three reproducible clinical phenotypes of ascites were identified with distinct risk profiles. The Vasodilatory-Synthetic Dysfunction phenotype was associated with a 3-fold increase in the risk of AKI that persisted after adjustment for MELD 3.0. No differences in waitlist mortality were observed, likely reflecting effective MELD-based transplant allocation that preferentially removes the highest-acuity patients from the waitlist.
Changes in organ allocation, technology, and regulatory policy have led to significant increases in deceased donor liver offers for transplantation. Expansion of potential donors is associated with inefficiencies, including increased liver nonutilization, resources, and complications. We evaluated the contribution of individual waitlisted candidates to the national allocation of deceased donor liver offers to understand characteristics of candidates with numerous offer turndowns. We performed an observational cohort study of the Scientific Registry of Transplant Recipients, including deceased donor liver offers in the United States between January 1, 2021, and December 31, 2024. We used standard and hierarchical multivariable logistic models to evaluate factors associated with high-frequency candidates (HFCs). There were 1,021,569 offers of 32,750 deceased donor livers to 55,124 waitlisted candidates with ≥1 offer. Waitlisted candidates had 10.4 months average waitlist follow-up and received a median of 9 (IQR=[4, 22]) offers. However, 46% of offers (n=468,699) went to 10% (HFC, n=5726), who had ≥45 offers over the period. HFC were disproportionally ages 18-39 (adjusted odds ratio [AOR]=1.58, 95% CI=1.33-1.86, relative to 70+), Black (AOR=1.31, 95% CI: 1.17-1.47, relative to White), type-O blood (AOR=1.14, 95% CI: 1.07-1.21, relative to type A), body mass index ≥35 kg/m 2 (AOR=1.17, 95% CI: 1.06-1.28, relative to body mass index=20-24 kg/m 2 ), MELD 12-17 (AOR=1.24, 95% CI: 1.15-1.34, relative to >25), metabolic dysfunction (AOR=1.32, 95% CI: 1.09-1.62, relative to cirrhosis) and history of portal vein thrombosis (AOR=1.34, 95% CI: 1.23-1.46). There was significant heterogeneity in HFC by transplant center (median=8%, IQR=[3%, 13%]), and centers with higher proportions of HFC had lower transplant rates and offer acceptance ratios ( p <0.001). HFCs who received transplants had fewer living donor transplants and transplanted with older age donors. Results indicate liver donor offers are disproportionately explained by a minority of candidates. Efforts to identify reasons for repetitive offer declines, strategic use of offer filters and transition of applicable candidates to inactive status may dramatically improve the efficiency of deceased donor liver allocation.
Coronary artery disease in candidates of living donor liver transplantation (LDLT) requires revascularization strategies balancing cardiac risk against end-stage liver disease complexity. Data on revascularization outcomes in this setting remain scarce. We conducted a single-center retrospective cohort study of consecutive adult recipients of LDLT requiring coronary revascularization between January 2017 and April 2025; the principal outcomes evaluated were 90-day and 1-year all-cause mortality and major adverse cardiac events. Of 371 recipients, significant coronary artery disease was identified in 26 (7.0%): 15 underwent staged percutaneous coronary intervention (PCI) and 11 underwent simultaneous coronary artery bypass grafting (CABG); off-pump CABG (OPCAB) was the preferred technique, in 10 of 11 cases (90.9%). Patients in the CABG group had more advanced liver disease (Child-Pugh class C 0% vs. 45.5%; median MELD-Na 10 vs. 16) and more complex coronary anatomy, with left main coronary disease confined to this group (0% vs. 36.4%). Ninety-day all-cause mortality was 3.8% (1/26; 95% CI: 0.1%-19.6%) and 1-year mortality 7.7% (2/26; 95% CI: 0.9%-25.1%); all deaths occurred in the CABG group from noncardiac sepsis. Cardiac mortality was 0% in both groups (PCI, 95% CI: 0.0%-21.8%; CABG, 95% CI: 0.0%-28.5%); 1-year major adverse cardiac event was 0%; 1-year CABG group survival was 81.8% (95% CI: 48.2%-97.7%). No stent thrombosis occurred despite a PCI-to-LDLT interval of 20-1505 days, reflecting the scheduling flexibility unique to living donor programs. The predominant procedure-specific complication was sternotomy-related pleural effusion (0% in the PCI group vs. 63.6% in the CABG group). These preliminary findings suggest the feasibility of both staged PCI and simultaneous CABG-LDLT when the strategy is individualized by coronary anatomy and hepatic reserve, with wide confidence intervals reflecting this small cohort and underscoring the need for multicenter validation.
BACKGROUND:Frailty adversely affects post-transplant outcomes in chronic liver disease (CLD). This study evaluated the feasibility and the impact of preoperative supervised aerobic and resistance exercises (SARE) on frailty and outcomes after living donor liver transplantation (LDLT). METHODS:This single-centre randomized controlled trial assigned the LDLT recipients to standard medical therapy (SMT) or SARE+SMT for 4 weeks pre-LDLT. Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), pulmonary function tests (PFTs) and postoperative outcomes were compared. RESULTS:Sixty patients, [54 (90%) males, 26 (43.33%) alcoholic liver disease, 18 (30%) NASH, median MELDNa of 22 (19-27) and CTP A 5 (8.33%), B 22 (36.67%), C 33 (55%) were randomised (30/group)]. Baseline parameters, LFI and SPPB were comparable. At enrolment, 46(76.67%) were pre-frail, 7(11.67%) frail and 53(88.33%) were sarcopenic. Seven(11.66%) patients died during workup, four lost to follow-up and 49 underwent LDLT. In SARE arm, 40% patients attended ≥5 exercise sessions. No adverse events occurred; recurrent admissions were hinderance to study adherence. Adjusted analysis showed similar LFI (p=0.92), SPPB (p=0.71) and PFT between groups. A borderline improvement in NIV discontinuation (p=0.05) and earlier chair and bipedal ambulation (p=0.10 and p=0.09, respectively) was observed with SARE. Significant correlations were observed for POD30 LFI [MV duration- r=0.56 (p=0.00), NIV duration- r=0.509 (p=0.00), hospital stay- r=0.547 (p=0.00) and ICU stay- r=0.563 (p=0.00)], with similar statistically significant correlations for POD14 and POD30 LFI, SPPB and PFTs. CONCLUSIONS:Preoperative SARE is safe and feasible in high MELD/ Child patients. LFI, SPPB, PFT, and postoperative outcomes were comparable between groups. SARE showed borderline improvement in ambulation and NIV discontinuation. Better LFI, SPPB, PFTs predicted improved clinical outcomes.
The survival benefit of liver transplantation (LT) for hepatocellular carcinoma (HCC) varies by waitlist dropout risk, yet allocation policy applies uniform prioritization, and center practices remain poorly characterized. We performed a retrospective cohort study using the United Network for Organ Sharing database, including LT candidates with HCC between February 4, 2020, and October 1, 2024. Low-dropout-risk (LDR) HCC was defined as MELD<15, Child-Pugh A, single lesion <3 cm, and AFP≤20 ng/mL at listing; all others were standard risk. Centers were classified as low-LDR (lowest quartile) or high-LDR (highest quartile) based on the proportion of their transplants that were LDR candidates with complete radiographic response (no viable tumor) on the last pre-LT imaging. Waitlist outcomes were analyzed with adjusted Fine-Gray competing-risk models. Among 7198 candidates across 93 centers, the proportion of LDR transplants varied widely across centers (range 0%-42%). In adjusted analyses, among standard-risk candidates, listing at a high-LDR rather than low-LDR center was associated with lower transplantation (SHR 0.81, 95% CI 0.72-0.90) and higher dropout (SHR 1.39, 95% CI 1.14-1.70) (both p <0.001). Waitlist outcomes for LDR candidates and post-transplant survival did not differ by center type. These findings suggest substantial center variation exists for LDR HCC and may disadvantage access among higher-need candidates despite similar post-transplant survival.
In adult dual left liver graft living donor liver transplantation (LDLT), composite rotation of the right-sided graft alters the bile duct-portal vein relationship, making bilateral duct-to-duct (D-D) reconstruction technically challenging. Although bilateral D-D preserves endoscopic access and avoids enteric reconstruction, no structured intraoperative strategy has been established. From 36 consecutive dual left graft LDLT procedures, we propose a practical approach based on bile duct-portal vein positional patterns and a 2-stage intraoperative assessment. Bilateral D-D was achieved in 26 patients (72.2%) without bile leak. Biliary stricture occurred in 38.5% and was managed endoscopically in 88.9% without surgical reintervention. Portal vein narrowing developed in 8 patients (22.2%), most often when the right graft bile duct lay deeply posterior to the portal vein after rotation (55.6% vs. 11.1%-12.5% in other patterns). Among patients with narrowing and long-term follow-up, all 4 conservatively managed grafts developed right graft atrophy, whereas none of the 3 managed with intraoperative portal vein stenting did; no mortality was attributable to narrowing. Bilateral D-D is therefore achievable when guided by intraoperative assessment of the bile duct-portal vein relationship after composite rotation: hepaticojejunostomy should be performed without hesitation in unfavorable configurations, and intraoperative portal vein stenting should be considered selectively when narrowing is detected. In carefully selected patients, bilateral D-D is a feasible strategy that preserves endoscopic access; these single-center observations are exploratory and warrant prospective validation.
Hepatic resection (HR) and liver transplantation (LT) are curative-intent treatments for hepatocellular carcinoma (HCC). Patients without cirrhosis are typically analyzed as a single group, obscuring potentially important differences between those with histologically normal liver and those with non-cirrhotic parenchymal disease. We aimed to characterize long-term outcomes following HR stratified by underlying parenchymal quality, with a contemporary LT cohort as an external benchmark. Retrospective cohort study of 662 adults undergoing curative-intent surgery for HCC at 2 tertiary centers (2010-2024). Resection patients (n=380) were stratified by non-tumor parenchymal histology into HR-Normal (n=84), HR-Diseased non-cirrhotic (n=159), and HR-Cirrhotic (n=137). A total of 282 LT recipients served as an external reference but were not entered into comparative models. Overall survival (OS) was analyzed by Kaplan-Meier and multivariable Cox regression, and recurrence by Fine-Gray competing-risks regression. Ninety-day mortality was low across resection strata (1.2%-3.2%). OS differed significantly across parenchymal groups (log-rank p =0.01), driven by superior outcomes in HR-Normal patients compared with both HR-Cirrhotic ( p =0.008) and HR-Diseased ( p =0.005). HR-Cirrhotic and HR-Diseased did not differ ( p =0.97). Five-year OS was 74.4%, 59.8% and 57.2%, respectively. On multivariable Cox regression, both cirrhosis (HR 2.03, 95% CI 1.16-3.54, p =0.01) and diseased non-cirrhotic parenchyma (HR 2.04, 95% CI 1.21-3.43, p =0.008) independently predicted death versus normal liver. Fine-Gray analysis confirmed higher recurrence risk in cirrhotic (sHR 2.09, p =0.01) and diseased non-cirrhotic (sHR 1.80, p =0.04) groups. The LT benchmark cohort achieved a 5-year OS of 82.4%. Histologically normal liver identifies a distinct HR subgroup with favorable oncologic outcomes. The conventional cirrhotic/non-cirrhotic dichotomy underestimates the prognostic impact of underlying parenchymal disease.
Donation after circulatory death (DCD) liver transplants (LTs) are associated with increased risk of post-LT acute kidney injury (AKI). This retrospective study aimed to examine the effect of continuous normothermic machine perfusion (NMP) on the incidence and stage of AKI in DCD LT. The incidence of AKI within 48 hours was compared between 507 NMP-DCD and 472 static cold storage (SCS)-DCD LT transplanted between January 1, 2016, and December 31, 2024. AKI developed in 337 (34%) patients. On univariate analysis, AKI rate was lower in NMP-DCD compared with SCS-DCD (28% vs. 41%, p <0.001). Stages 2 and 3 AKI at 48 hours and renal replacement therapy (RRT) within the first 3 weeks were also lower in NMP-DCD compared with SCS-DCD ( p <0.001). After adjusting for multiple recipient, donor, and intraoperative factors using multivariate logistic regression, NMP-DCD was independently associated with a 37% lower odds of AKI (aOR: 0.63, CI: 0.46-0.85, p =0.003) and 55% lower odds of stages 2 and 3 AKI (aOR: 0.45, CI: 0.29-0.69, p <0.001) compared with SCS-DCD. To mitigate for the era effect and other unmeasured confounders, an inverse probability of treatment weighting (IPTW) analysis was performed using a propensity score model with average treatment effect (ATE). After weighting for multiple factors, NMP-DCD was associated with lower odds of AKI at 48 hours (OR: 0.65, CI: 0.53-0.81, p =0.001), stages 2 and 3 AKI at 48 hours (OR: 0.60, CI: 0.42-0.85, p =0.02), and RRT at day 7 (OR: 0.31, CI: 0.13-0.65, p =0.003) compared with SCS-DCD. In conclusion, compared with SCS-DCD, NMP-DCD was independently associated with lower odds of AKI at 48 hours, of stages 2 and 3 AKI at 48 hours from LT, and of RRT requirement at day 7 from LT, an effect that extended for the first 3 post-LT weeks.
