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Current Challenges and New Perspectives in Liver Transplantation

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 4665

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Special Issue Editors

Dr. Anna Mrzljak

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Guest Editor

Liver Transplant Center, University Hospital Center Zagreb, Kispaticeva 12, 1000 Zagreb, Croatia
Interests: transplant hepatology; post-transplant outcomes; alcoholic liver disease; HCC

Dr. Quirino Lai

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Guest Editor

General Surgery and Organ Transplantation Unit, Sapienza University of Romne, AOU Policlinico Umberto I Rome Viale del Policlinico 155, 00161 Rome, Italy
Interests: post-transplant outcomes; HCC; CCC; living donor; liver trasnplantation
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Special Issue Information

Dear Colleagues,

We would like to invite you to contribute to this Special Issue, “Current Challenges and New Perspectives in Liver Transplantation”. Liver transplantation (LT) has evolved significantly over the past few decades, becoming a life-saving treatment for various acute and chronic liver diseases. Despite major advances in surgical techniques, immunosuppression, and patient selection, LT still faces several persistent challenges, including donor organ shortage, complications from long-term immunosuppression, the recurrence of primary liver diseases, and disparities in access to transplantation. Additionally, emerging issues, such as transplantation in the context of metabolic dysfunction-associated liver disease (MASLD), hepatocellular carcinoma beyond traditional criteria, and transplantation for acute-on-chronic liver failure, are reshaping the landscape and require updated, evidence-based approaches. With the advent of precision medicine, machine learning, and minimally invasive diagnostics, new perspectives present opportunities to improve outcomes and individualized care.

This Special Issue aims to provide a comprehensive overview of the current state and future directions in liver transplantation. It seeks high-quality contributions that align with the journal’s scope by advancing our understanding of clinical research in hepatology and transplantation medicine. Our goal is to compile a diverse range of studies that reflect innovative thinking, multidisciplinary collaboration, and the latest developments in this dynamic field.

Topics of interest include (but are not limited to) the following:

Expanding indications for liver transplantation;
Biomarkers and imaging in transplant evaluation and follow-up;
Post-transplant complications and immunosuppression strategies;
Outcomes in special populations (elderly, pediatric, and HIV-positive recipients);
Health equity and access to transplantation;
Artificial liver support systems and bridge-to-transplant strategies;
Recurrent and de novo malignancies post transplant;
The role of artificial intelligence and precision medicine in transplant decision making.

Original research articles and comprehensive review papers are welcome.

We look forward to receiving your contributions and hope to advance this field of research and foster new collaborations.

Dr. Anna Mrzljak
Dr. Quirino Lai
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

liver transplantation
graft survival
immunosuppression
organ allocation
hepatocellular carcinoma
MASLD
donor shortage
transplant outcomes
innovation

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Published Papers (6 papers)

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Research

13 pages, 744 KB

Open AccessArticle

Peak Lactate During the First Postoperative Day Predicts 90-Day Graft Loss After Liver Transplantation

by Quirino Lai, Borna Cutic, Licia Iannello, Ivona Hanzek, Fabio Melandro, Robert Baronica, Gianluca Mennini, Vibor Sesa, Massimo Rossi and Anna Mrzljak

J. Clin. Med. 2026, 15(7), 2698; https://doi.org/10.3390/jcm15072698 - 2 Apr 2026

Viewed by 324

Abstract

Background: Early identification of liver transplant (LT) recipients at risk of graft failure is crucial to allow timely retransplantation. Lactate levels have been proposed as markers of graft dysfunction, although their optimal timing and predictive value remain uncertain. This study aimed to investigate the prognostic role of early postoperative lactate measurements for predicting 90-day graft loss after LT and compare their performance with established early allograft dysfunction scores. Methods: This retrospective observational study included adult patients undergoing their first LT at the Sapienza University of Rome (Italy) between 2013 and 2021, with external validation in an independent cohort from Zagreb University (Croatia) between 2022 and 2025. Lactate levels were evaluated at declamping, at the end of transplantation, and as the peak value within the first postoperative day. Their predictive ability for 90-day graft loss was compared with Early Allograft Dysfunction (EAD) and the Model for Early Allograft Function (MEAF) score using receiver operating characteristic (ROC) analysis. Results: A total of 268 LT recipients were analyzed (178 Sapienza and 90 Zagreb). Ninety-day graft loss occurred in 25 (14.0%) patients in Sapienza and 10 patients (11.1%) in Zagreb. A lactate peak within the first postoperative day showed the highest discriminative ability for predicting graft loss in both cohorts (Sapienza: AUC 0.87, 95%CI 0.77–0.98, p < 0.001; Zagreb: AUC 0.79, 95%CI 0.62–0.97, p = 0.003). This outperformed EAD and MEAF. A lactate peak cutoff of 5.0 mmol/L (75th percentile) resulted in 80.0% sensitivity and 86.3% specificity in Sapienza and 80.0% sensitivity and 68.7% specificity in Zagreb. Higher thresholds increased specificity, reaching 98.7% and 95.0% at 8.4 mmol/L in the Sapienza and Zagreb cohorts, respectively. Patients with a lactate peak ≥ 5.0 mmol/L showed significantly higher 90-day graft loss compared with those below the threshold in both cohorts (Sapienza: 47.6% vs. 4.7%, p < 0.001; Zagreb: 25.0% vs. 5.0%, p = 0.004). Conclusions: The peak lactate value during the first postoperative day represents a simple and accurate biomarker for predicting early graft loss after LT. Its superior predictive performance compared with commonly used EAD-related scores suggests that the lactate peak may represent a valuable tool for early postoperative risk stratification. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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19 pages, 2316 KB

Open AccessArticle

Impact of Non-Malignant Portal Vein Thrombosis in Recipients with Metabolic Dysfunction-Associated Steatotic Liver Disease Compared to Other Transplant Indications

by Esli Medina-Morales, Yash Shah, Anastasia Xynogala, Mohamed Ismail, Ritik M. Goyal, Yazan Abboud, Hirsh D. Trivedi, Thomas D. Schiano and Keri E. Lunsford

J. Clin. Med. 2026, 15(5), 1787; https://doi.org/10.3390/jcm15051787 - 27 Feb 2026

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Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of portal vein thrombosis (PVT), which may negatively affect post-liver transplant (LT) outcomes. We aimed to evaluate the impact of PVT on post-LT outcomes in MASLD versus non-MASLD recipients and assess outcomes in MASLD patients with PVT who received donation after circulatory death (DCD) grafts. Methods: Using the UNOS database, we analyzed adult LT recipients from 2002 to 2022. Kaplan–Meier and Cox regression models were used to assess one-year post-LT outcomes. Results: Among 46,933 LT recipients, 20% had MASLD (15% PVT prevalence) and 80% had non-MASLD etiologies (9% PVT prevalence). Overall, 3051 recipients (6.5%) received DCD grafts. PVT at the time of transplant was associated with significantly higher risks of all-cause mortality, graft failure, and death-censored graft failure (DCGF) in both MASLD and non-MASLD groups (p < 0.05), although no significant differences were observed between the two groups. In the DCD subgroup, MASLD recipients with PVT had a significantly higher risk of all-cause mortality compared to non-MASLD recipients without PVT (adjusted hazard ratio [aHR] 2.24, 95% CI 1.17–4.28, p = 0.01), but no differences were observed for graft failure or DCGF. Conclusions: PVT at the time of transplant is associated with poorer survival in MASLD and non-MASLD recipients. No difference was found between the two groups. In candidates receiving DCD grafts, the presence of PVT at time of transplant was associated with a marked increase in mortality risk, although this finding requires further validation in larger cohorts. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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12 pages, 935 KB

Open AccessArticle

Should We Continue Liver Transplantation in Spain for Hepatic Metastases from Neuroendocrine Tumors?

by Andrea Boscà, Eva M. Montalvá, Marina Vila-Tura, Laura Lladó, Víctor López, Mikel Gastaca, Santiago Tomé, José M. Ramia, Javier Nuño, Fernando Rotellar, María Pérez, Óscar Caso, Mᵃ Mar Achalandabaso, Isabel Jaén, Carmen García, Pablo Ramírez and Rafael López-Andújar

J. Clin. Med. 2026, 15(3), 938; https://doi.org/10.3390/jcm15030938 - 23 Jan 2026

Viewed by 528

Abstract

Background/Objectives: Despite the long-standing history of liver transplantation (LT) in Spain, no multicenter study has reviewed national outcomes for LT in metastatic neuroendocrine tumors (NETs). In the current era of transplant oncology, auditing these results is essential to refine patient selection and improve long-term outcomes. Methods: This retrospective observational study analyzed data from 13 centers, including 91 patients who underwent LT for NET between 1995 and 2024. Patients were stratified into two groups: Milan IN (those meeting the Milan criteria) and Milan OUT (the remainder). Results: Recurrence occurred in 57.1% of cases, and overall mortality was 51.6%. Of the 91 patients, 71 (78.0%) were Milan IN and 20 (22.0%) were Milan OUT. Five-year overall survival was 71.0% in Milan IN and 58.0% in Milan OUT, with a statistically significant difference. The 5-year disease-free survival (DFS) rate was 58.8% in Milan IN and 36.3% in Milan OUT; this difference was not statistically significant. Conclusions: In conclusion, strict adherence to Milan criteria and incorporation of modern prognostic factors are critical to optimize long-term survival in LT for NET. While the overall outcomes in this historical cohort are modest, future improvements are expected through more rigorous selection and the potential use of bridging or downstaging therapies. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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10 pages, 383 KB

Open AccessArticle

Biliary Reconstruction in Liver Transplantation with Primary Sclerosing Cholangitis: Roux-en-Y Hepaticojejunostomy or Duct-to-Duct Anastomosis?

by Peter T. Dancs, Mira C. Pohlmann, Jan Bednarsch, Jassin Rashidi-Alavijeh, Sophia M. Schmitz, Andreas Kroh, Florian Ulmer, Florian W. R. Vondran, Ulf P. Neumann, Dieter P. Hoyer and Daniel Heise

J. Clin. Med. 2025, 14(23), 8518; https://doi.org/10.3390/jcm14238518 - 1 Dec 2025

Viewed by 580

Abstract

Background/Objectives: Biliary reconstruction in liver transplantation (LT) for primary sclerosing cholangitis (PSC) is controversial. A Roux-en-Y hepaticojejunostomy (HJ) is associated with fewer anastomotic strictures, while a duct-to-duct reconstruction (DD) shows a decreased rate of cholangitis and preserves anatomy for endoscopy. The aim of our study was to analyze patient survival and postoperative outcomes after LT for PSC based on the type of reconstruction in two high-volume LT centers. Methods: We included 94 PSC patients who underwent a primary LT between 2010 and 2024. The association of biliary reconstruction with patient survival was assessed with the Kaplan–Meier method. Predictors of mortality and postoperative complications were identified via Cox and logistic regression. Results: In total, 42 patients received an HJ and 52 patients received a DD. There was no difference in patient survival or major complications. DD resulted in an increased number of anastomotic strictures, whereas anastomotic insufficiency, ischemia, cholangitis, and the need for revision surgery showed no difference. The choice of biliary reconstruction technique was not a predictor for mortality or major complications. Conclusions: Both types of biliary reconstruction are effective for PSC patients, with comparable patient survival and postoperative outcomes. Although DD is associated with an increased number of strictures, endoscopic treatment options provide a feasible solution. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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13 pages, 849 KB

Open AccessArticle

Outcomes from Referral to Transplant for Patients with MASLD: A California Liver Network Study

by Tiffany Y. Lim, Justin A. Steggerda, Hirsh Trivedi, Michael Luu, Aarshi Vipani, Michie A. Adjei, Jasleen Singh, Kali Zhou, Allison Kwong, Monica Tincopa, Irine Vodkin, Veeral Ajmera, Neil Mehta, Chris E. Freise, Mignote Yilma, Ryutaro Hirose, Alexander Kuo and Steven A. Wisel

J. Clin. Med. 2025, 14(21), 7841; https://doi.org/10.3390/jcm14217841 - 4 Nov 2025

Cited by 1 | Viewed by 842

Abstract

Background: Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is becoming a leading indication for liver transplantation in the United States. In this growing recipient population, the combined effects of underlying liver disease etiology and associated comorbidities on the evaluation pathway to transplantation warrant closer examination of patient outcomes. Methods: We analyzed adult liver transplant referrals (n = 9981) from the California Liver Network, a multi-center retrospective cohort spanning six high-volume California transplant centers between 2018 and 2020. A total of 6709 patients who underwent formal evaluation were included. Patients were stratified by MASLD vs. non-MASLD etiology and compared for demographics, comorbidities, transplant evaluation timelines, listing rates, and outcomes. Results: MASLD patients (n = 1477) were older, had higher BMI, and had greater prevalence of metabolic comorbidities than non-MASLD patients (n = 5232; p < 0.001 for all). Compared to non-MASLD candidates, MASLD patients were more likely to be waitlisted (OR 1.52, 95% CI 1.33–1.74; p < 0.001). However, MASLD and non-MASLD patients had no statistically significant difference in the rate of transplant (p = 0.182), with clinically similar but statistically inferior post-transplant survival outcomes at 5 years post-transplant (88% vs. 83%; p = 0.014). Competing-risk analysis showed that MASLD candidates had higher cumulative incidence of death on the waitlist (p < 0.001), although MASLD was not independently associated with waitlist mortality when adjusting for covariates (p = 0.300). MASLD patients demonstrated increased mortality following waitlist removal (HR 1.64, 95% CI 1.14–2.35; p = 0.008), primarily among those removed for clinical deterioration (HR 1.50, 95% CI 1.01–2.23; p = 0.044). Conclusions: MASLD patients face unique challenges in liver transplant evaluation. MASLD patients are associated with higher comorbidities, increased incidence of waitlist mortality, and significantly higher mortality rate following waitlist removal. However, transplantation provides significant survival benefit with comparable outcomes to non-MASLD recipients; thus, early access to transplant may optimize outcomes for MASLD liver transplant candidates. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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15 pages, 1741 KB

Open AccessArticle

Outcomes in Asymptomatic Patients Undergoing Coronary Revascularization Before Liver Transplantation

by Goyal Umadat, Jennifer Lee, Jordan C. Ray, Ryan M. Chadha, Yaohua Ma, Hanna J. Sledge, Surakit Pungpapong, Leslie E. Janik, Dilip Pillai, Abdallah El Sabbagh, Peter Pollak and Shahyar M. Gharacholou

J. Clin. Med. 2025, 14(19), 7067; https://doi.org/10.3390/jcm14197067 - 7 Oct 2025

Viewed by 915

Abstract

Background: Coronary artery disease (CAD) is common among liver transplantation (LT) candidates, yet whether pre-transplant percutaneous coronary intervention (PCI) improves post-LT outcomes remains uncertain. Methods: We conducted a single-center, Institutional Review Board-approved cohort study of adults undergoing LT from 2005 to 2025. Asymptomatic candidates with significant stenosis on invasive angiography were included; prior coronary artery bypass grafting was excluded. The primary endpoint was major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke/transient ischemic attack, new systolic dysfunction, post-LT coronary revascularization, or all-cause death). Results: Among 111 patients (median age 65 years; 84% male), 66 (59%) underwent PCI and 45 (41%) were managed medically. Over a median 32 months of follow-up, 61 patients (55%) experienced MACE. Composite MACE did not differ between PCI and non-PCI groups (52% vs. 60%, p = 0.40; log-rank p = 0.59). Fine–Gray modeling showed no association of PCI with MACE; independent predictors were prior MI (HR 1.81, 95% CI 1.01–3.24) and pre-transplant dialysis (HR 2.13, 95% CI 1.07–4.24). Major bleeding occurred in 7%. Matched and era-stratified analyses were concordant. Conclusions: In asymptomatic LT candidates with angiographically severe CAD, pre-LT PCI was not associated with a lower incidence of post-LT MACE. Full article

(This article belongs to the Special Issue Current Challenges and New Perspectives in Liver Transplantation)

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