Post-liver Transplantation Research Articles

Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation.

Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

Insights and perspectives: EUS in post-liver transplantation care

Insights and perspectives: EUS in post-liver transplantation care

Imaging of Ischemic Cholangiopathy Following Donation after Circulatory Death Liver Transplant.

Ischemic cholangiopathy (IC) is the leading cause of inferior long-term outcomes following donation after circulatory death (DCD) liver transplant. Biliary strictures related to IC are nonanastomotic strictures (NASs) by definition and involve the donor hepatic ducts proximal to the anastomosis, compared with postsurgical anastomotic strictures that form due to fibrotic healing. IC-related NASs can be microangiopathic with patent hepatic artery or macroangiopathic with occluded or stenotic hepatic artery. Recently, IC with NASs have been described to have four distinct patterns at imaging: diffuse necrosis, multifocal progressive, confluence dominant, and minor form, which correlate clinically with graft prognosis. Severe IC can lead to ductal wall breakdown with subsequent bile leaks that can cause significant patient morbidity, with imaging playing a vital role in diagnosis and guiding intervention. IC also predisposes the transplanted liver to biliary stasis and subsequent formation of stones, casts, and sludge. Some cases of posttransplant biliary stricturing are not IC but are a sequela of reflux cholangitis seen with choledochojejunal anastomosis. Other biliary findings in the posttransplant liver can be explained by sphincter of Oddi dysfunction that results from denervation. The authors describe and comprehensively categorize the various IC types and their imaging patterns at MRI and MR cholangiopancreatography, review the prognostic significance of these imaging patterns, and discuss imaging features of additional biliary complications associated with IC after DCD liver transplant. ©RSNA, 2024 Supplemental material is available for this article.

Maintenance immunosuppressive therapy in liver transplantation: results from CESIT study, an Italian retrospective cohort study

ObjectivesTo investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk–benefit profiles in clinical practice.DesignRetrospective multicentrer cohort study.SettingFour Italian regions (Lombardy, Veneto, Lazio, Sardinia).MethodsData were...

Impact of phosphatidylethanol in the surveillance for alcohol use in post-liver transplant population: A retrospective study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation in the United States. The aim of this study was to describe the impact of phosphatidylethanol (PEth) in the surveillance for alcohol use after liver transplantation. We conducted a single-center retrospective study to assess the impact of phosphatidylethanol (PEth) for the surveillance of alcohol use and its correlation to health outcomes. We compared orthotopic liver transplant (OLT) recipients for ALD transplanted between 2016 and 2018, before the introduction of PEth, to those transplanted between 2019 and 2022, after the introduction of PEth. Alcohol relapse versus nonrelapse cohorts were also compared. Follow-up time for all cohorts was limited to 3 years post-OLT. Continuous variables were analyzed with an independent t-test and categorical variables with Fischer's exact test and chi-square test. The Kaplan-Meier method and log-rank test were used to assess alcohol-free survival. We reviewed 263 patients who were transplanted for ALD; 46 (17.5%) patients were noted to have at least one episode of alcohol relapse after their transplant. Patients with alcohol relapse had more frequent episodes of elevated liver enzymes compared with nonrelapsed patients (4.35 episodes vs. 2.46 episodes respectively, p < 0.001). The number of hospitalizations was also noted to be elevated among relapsed versus nonrelapsed patients; however, this was not statistically significant (2.85 vs. 2.50 respectively, p = 0.307). When comparing relapse rates before and after the introduction of PEth, relapses were notably detected more frequently after the introduction of PEth (17% vs. 7%, p = 0.012). No difference was noted in rates of mortality between patients who did or did not relapse. Overall, PEth is an effective surveillance tool in the postliver transplant population to monitor for alcohol relapse. Early detection of relapse can lead to opportunities for early intervention to avoid alcohol-related complications.

Early Prediction of Acute Kidney Injury in Living Donor Liver Transplantation by Serum Cystatin C Concentration at the End of the Surgery.

Acute kidney injury (AKI) is a prevalent complication of liver transplantation, leading to prolonged hospital or intensive care unit stay and significant morbidity. Recently, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have been investigated for their potential role in the early detection of AKI in liver transplantation patients. Our study comprised 60 patients with end-stage liver disease undergoing living donor liver transplantation. Based on the postoperative development of AKI, the patients were categorised into two groups: the AKI group comprising 22 patients and the non-AKI group comprising 38 patients. Serum cystatin C and urine NGAL levels were measured twice: immediately after induction of anaesthesia (baseline) and at the end of the surgery. The overall incidence of AKI was 36.66%. The mean cystatin C level measured at the end of the surgery was significantly higher in the AKI group (1.12 ± 0.40 mg/L) than in the non-AKI group (0.82 ± 0.27 mg/L) [P = .001]. The receiver operating characteristic curve for the postoperative cystatin C biomarker demonstrated a significant difference between the AKI and non-AKI groups [area under the curve: 0.71, P = .007]. However, baseline cystatin C and urine NGAL levels did not significantly differ between the groups. Cystatin C levels measured at the end of the surgery showed a better predictive value and higher accuracy in identifying post-liver transplantation patients with AKI than baseline cystatin C and urine NGAL.

Key genes and immune pathways in T-cell mediated rejection post-liver transplantation identified via integrated RNA-seq and machine learning

Liver transplantation is the definitive treatment for end-stage liver disease, yet T-cell mediated rejection (TCMR) remains a major challenge. This study aims to identify key genes associated with TCMR and their potential biological processes and mechanisms. The GSE145780 dataset was subjected to differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms to pinpoint key genes associated with TCMR. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory networks were constructed to ascertain the biological relevance of these genes. Expression validation was performed using single-cell RNA-seq (scRNA-seq) data and liver biopsy tissues from patients. We identified 5 key genes (ITGB2, FCER1G, IL-18, GBP1, and CD53) that are associated with immunological functions, such as chemotactic activity, antigen processing, and T cell differentiation. GSEA highlighted enrichment in chemokine signaling and antigen presentation pathways. A lncRNA-miRNA-mRNA network was delineated, and drug target prediction yielded 26 potential drugs. Evaluation of expression levels in non-rejection (NR) and TCMR groups exhibited significant disparities in T cells and myeloid cells. Tissue analyses from patients corroborated the upregulation of GBP1, IL-18, CD53, and FCER1G in TCMR cases. Through comprehensive analysis, this research has identified 4 genes intimately connected with TCMR following liver transplantation, shedding light on the underlying immune activation pathways and suggesting putative targets for therapeutic intervention.

Extracorporeal membrane oxygenation ameliorate hepatic injury in brain death rat donors with hemodynamic instability.

Donation after brain death (DBD) serves as the primary source for liver transplantation. However, livers obtained through DBD often incur damage due to unstable hemodynamics, potentially impacting transplantation outcomes. Extracorporeal Membrane Oxygenation (ECMO) emerges as an optimal technique for donor liver retrieval and has found application in clinical settings. Despite its clinical implementation, the precise mechanisms through which ECMO enhances liver functions remain elusive. This study aims to investigate the mechanisms underlying how ECMO ameliorates liver function in brain-dead donors. We randomly assigned 18 male Sprague-Dawley (SD) rats (350 ± 50 g) into three groups: Con (n = 6), DBD-assisted drug (n = 6), and DBD-assisted ECMO (n = 6). After 3 h of ECMO, the rats were sacrificed. We assessed and compared changes in heart rate, blood pressure, cumulative liver damage (evaluated through HE and TUNEL staining), serum levels of AST and ALT, alterations in serum oxidative stress factors (MDA, H2O2, SOD, and 8-OHdG), and serum concentrations of related inflammatory factors (interleukin [IL]-1β, IL-6, IL-8, and TNF-α) among rats in the Con, DBD-assisted drug, and DBD-assisted ECMO groups. Subsequently, we established a rat orthotopic liver transplantation (OLT) model and transplanted livers obtained through the aforementioned methods. The post-transplantation status of the livers was observed. After 3 h of brain death, liver injury worsened, accompanied by a significant increase in serum transaminases, inflammatory responses, oxidative stress, and TUNEL staining. Strikingly, ECMO not only stabilized hemodynamics after DBD but also mitigated liver damage, leading to an alleviated status post liver transplantation. ECMO stabilizes hemodynamics, attenuates inflammatory responses and oxidative stress, thereby enhancing the quality of liver grafts for transplantation.

Robust Predictive Performance of the SALT-M Score for Clinical Outcomes in Asian Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade. The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018). SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M.

Less is more: The use of a single biodegradable stenting to treat biliary anastomotic strictures in pediatric liver transplantation.

To report our experience of using biodegradable biliary stents for anastomotic biliary strictures in pediatric liver transplant patients. Analysis of a retrospective data collection from January 2014 to January 2023, including all pediatric liver transplant recipients in our center treated for anastomotic biliary strictures with biodegradable biliary stents (BBS). In phase 1 (2014-2019), there was an initial percutaneous transhepatic cholangiography (PTC) with anastomotic dilatation followed two weeks after by a second PTC with BBS insertion. In phase 2 (2019-2023), the BDS were placed shortly after anastomotic biliary strictures dilatation, requiring only one PTC. All patients were followed up with routine tests and ultrasound. Forty-six anastomotic biliary strictures were diagnosed in 43 pediatric liver transplant recipients with a median of 6.7 months post-liver transplantation (0.1-246.8 months). Eight out of 46 anastomotic biliary strictures (17.4%) treated with biodegradable biliary stents relapsed (median recurrence time: 6.5 months; 1.6-17.0 months). Four resolved with further BBS placement; only four needed surgical revision (8.7%) after a median follow-up time of 43.9 months (0.3-106.3). There were no differences in anastomotic biliary strictures recurrence rate, time between stent placement and recurrence, or the presence of cholangitis based on whether the BBS was deployed in one or two steps. Patients with end-to-end anastomosis had a higher anastomotic biliary strictures recurrence (or 10.8; 1.4-81.3, p=0.008) than those with bilioenteric anastomosis. The use of biodegradable stents stents could be good option for treating anastomotic biliary strictures in pediatric liver transplant patients, with our series showing a success rate of over 90% and an average follow-up of 43.9 months.

Role of sonography in detection and evaluation of post liver transplant complications.

To evaluate the role of sonography in revealing and characterizing liver transplant complications based on gray scale and color Doppler, describe the normal Doppler findings, and discuss the significance of distinguishing normal transient changes in the spectral waveform from findings that may suggests ominous complications. We carried out a retrospective cross-sectional study at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. The medical records and imaging studies of a total of 122 candidates who underwent transplantation between January 2016 to February 2022 were reviewed. Our results showed that most patients were males with the most frequent age group being those between 54-71 years. Hepatitis B virus and hepatic cellular carcinoma were the most common indications for transplants. A total of 95 patients received a graft from a living related donor. Regarding complications, biliary issues (including leaks and ducts dilation) were the second most frequent complication after collections. Vascular complications represented 7.4% of all complications and was the leading cause of death in 4.8% of cases. Among all vascular issues encountered during liver transplant, portal vein thrombosis was the most predominant. In respect to Doppler findings, portal vein velocities and resistive index of hepatic artery had re-averaged within 7-10 post-operative days in most patients. Ultrasound plays crucial role in the post-operative management of compilations, facilitating early detection, which is substantial for the graft survival.

S1979 MELD-Psoas: A New Composite Predictive Score for Post-liver Transplant Outcomes

S1979 MELD-Psoas: A New Composite Predictive Score for Post-liver Transplant Outcomes

Case Report: When Arteries Betray: Massive Post-transplantation Hemorrhage

Hepatic artery pseudoaneurysm is a rare complication that may occur in the setting of liver transplantation and other traumatic instrumentation of the hepatobiliary system. This condition poses a significant morbidity and mortality risk and must be diagnosed and intervened upon emergently. Herein we present a case of hepatic artery pseudoaneurysm complicated by hemorrhagic shock in the setting of a post-liver transplant biliary leak. In this case, the patient was ultimately diagnosed via hepatic angiogram, treated with hepatic artery embolization, and required subsequent retransplantation. The objective of this case was to demonstrate the importance of maintaining a high clinical suspicion for hepatic artery pseudoaneurysm in the post-transplant setting, emphasize the use of computed tomography angiography as a primary diagnostic tool, and involving interventional radiology early in the treatment course.

S1980 Assessing the Role of Donated Medications in Post-liver Transplant Patients

S1980 Assessing the Role of Donated Medications in Post-liver Transplant Patients

Evaluating the yield of digital single operator cholangioscopy in posttransplant biliary strictures after unsuccessful guidewire placement with ERCP.

Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D-SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods. This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased-donor liver transplant recipients undergoing D-SOC for biliary strictures who have failed conventional methods to achieve biliary access were included. Between July 2017 to April 2022, eighteen patients underwent D-SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D-SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D-SOC. In two of these patients, use of D-SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D-SOC cholangitis. D-SOC is effective at achieving guidewire access in post-liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery.

Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience.

The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8kPa ± 3.2) compared to patients with F0 fibrosis (5.2kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1kPa ± 1.5) (p = 0.041), on ANOVA. Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.

Machine learning for post-liver transplant survival: Bridging the gap for long-term outcomes through temporal variation features

BackgroundThe long-term survival of liver transplant (LT) recipients is essential for optimizing organ allocation and estimating mortality outcomes. While models like the Model-for-End-Stage-Liver-Disease (MELD) predict 90-day mortality on the waiting list, they do not predict post-LT survival accurately. There is a need for predictive models that can forecast post-LT survival beyond the immediate period after transplantation. MethodThis study introduces new temporal variation features for predicting post-LT survival during the waiting list period. Cox Proportional-Hazards regression (CoxPH), Random Survival Forest (RSF), and Extreme Gradient Boosting (XGB) models are utilized, along with patient demographics and waiting list duration. Data from 716 LT patients from the University of Minnesota CTSI (2011–2021) are used to develop, evaluate, and compare post-LT survival prediction models. ResultsThe temporal variation features, particularly when combined with the RSF model, proved most effective in predicting post-LT survival, with a C-index of 0.71 and an IBS of 0.151. This outperformed the predictive capability of the most recent MELD score, which had a C-index of <0.51 in the same cohort. ConclusionsIncorporating temporal variation features with the RSF model enhances long-term post-LT survival predictions. These insights can assist clinicians and patients in making more informed decisions about organ allocation and understanding the utility of LT, ultimately leading to improved patient outcomes.

Optimizing Piperacillin Dosing in Pediatric Liver Transplant Recipients: A Case Series.

Pathophysiological changes post-liver transplantation impact the pharmacokinetics and pharmacodynamics of antibiotics. Piperacillin, often used in combination with tazobactam, is a key antibiotic after transplantation to its broad-spectrum activity, but there is a lack of specific pharmacokinetic data in this population. This study aims to describe the pharmacokinetic parameters and target attainment of piperacillin in pediatric liver transplant recipients. Patients with preserved renal function (estimated glomerular filtration rate > 50 mL/min/1.73 m2) receiving intravenous piperacillin-tazobactam at 112.5 mg/kg every 8 h (100 mg piperacillin/12.5 mg tazobactam), with a rapid infusion (0.5-1 h), were included. Two blood samples per child were collected during the same interval within 48 h of starting therapy. A Bayesian approach was applied to estimate individual pharmacokinetic parameters and perform dosing recommendations against Enterococcus spp., Enterobacterales and Pseudomonas aeruginosa. Eight patients with median age of 8 months were included. Median piperacillin clearance and central volume of distribution for the cohort were 11.11 L/h/70 kg and 9.80 L/70 kg, respectively. Seven patients (87.5%) presented with concentrations below the target of 100% fT > MIC. Simulations suggested that these patients required more frequent dosing and extended duration of infusion to ensure target attainment. One patient (12.5%) had trough concentrations that exceed 16 mg/L and could receive a lower daily dose. This case series highlights the importance of personalized therapy in pediatric liver transplant recipients due to the unpredictable and highly variable piperacillin pharmacokinetics in this population.

Validation of the R3-AFP model for risk prediction of HCC recurrence after liver transplantation in the SiLVER randomized clinical trial.

Explant-based models for assessing HCC recurrence after liver transplantation serve as the gold standard, guiding post-liver transplantation screening and immunosuppression adjustment. Incorporating alpha-fetoprotein (AFP) levels into these models, such as the novel R3-AFP score, has notably enhanced risk stratification. However, validation of these models in high-evidence data is mandatory. Therefore, the aim of the present research was to validate the R3-AFP score in a randomized clinical trial. We analyzed the intention-to-treat population from the 2-arm SiLVER trial (NCT00355862), comparing calcineurin-based ([calcineurin inhibitors]-Group A) versus mammalian target of rapamycin inhibitors-based (sirolimus-Group B) immunosuppression for post-liver transplantation HCC recurrence. Competing risk analysis estimated sub-hazard ratios, with testing of discriminant function and calibration. Overall, 508 patients from the intention-to-treat analysis were included (Group A, n = 256; Group B, n = 252). The R3-AFP score distribution was as follows: 42.6% low-risk (n = 216), 35.7% intermediate-risk (n = 181), 19.5% high-risk (n = 99), and 2.2% very-high-risk (n = 11) groups. The R3-AFP score effectively stratified HCC recurrence risk, with increasing risk for each stratum. Calibration of the R3-AFP model significantly outperformed other explant-based models (Milan, Up-to-7, and RETREAT), whereas discrimination power (0.75 [95% CI: 0.69; 0.81]) surpassed these models, except for the RETREAT model ( p = 0.49). Subgroup analysis showed lower discrimination power in the mammalian target of rapamycin group versus the calcineurin inhibitors group ( p = 0.048). In conclusion, the R3-AFP score accurately predicted HCC recurrence using high-quality evidence-based data, exhibiting reduced performance under mammalian target of rapamycin immunosuppression. This highlights the need for further research to evaluate surveillance schedules and adjuvant regimens.