Normothermic regional perfusion (NRP) adoption for donation after circulatory death (DCD) liver transplantation in the United States has been growing, but there remains a higher rate of non-utilization of NRP DCD liver g...Normothermic regional perfusion (NRP) adoption for donation after circulatory death (DCD) liver transplantation in the United States has been growing, but there remains a higher rate of non-utilization of NRP DCD liver grafts as compared with donation after brain death liver grafts. Six transplant centers and 1 organ procurement organization (OPO) with substantial NRP liver procurement experience performed retrospective reviews of all NRP procurement attempts from September 1, 2021, until March 1, 2024, identifying opportunities for utilization. Five of the 6 transplant centers had prospectively collected data on all accepted livers with NRP intent. The transplant center's intention to utilize DCD donors included 329 livers accepted for transplantation before withdrawal, 252 (76.6%) potential donors expired within the hospital timeframe for donation, and 168 (66.7%) livers were transplanted. Fifty-seven opportunities for utilization were identified by transplant centers, plus 11 from the OPO: most were due to exceeding a functional warm ischemic time limit (n=26), other reasons (n=17), and functional assessment (n=16). The lessons learned by centers in this study provide guidance for newer NRP centers and for OPOs in identifying opportunities for utilization of NRP DCD grafts that have historically been declined.
Primary sclerosing cholangitis (PSC) is a progressive fibroinflammatory disease characterized by multifocal biliary strictures, recurrent cholangitis, and a markedly increased lifetime risk of cholangiocarcinoma (CCA). E...Primary sclerosing cholangitis (PSC) is a progressive fibroinflammatory disease characterized by multifocal biliary strictures, recurrent cholangitis, and a markedly increased lifetime risk of cholangiocarcinoma (CCA). Endoscopic retrograde cholangiopancreatography (ERCP) remains central to the diagnosis of CCA and management of PSC-related complications. This review synthesizes current evidence guiding the use of ERCP in patients with PSC, highlighting the importance of careful patient selection to mitigate adverse events. We review traditional ERCP techniques for the evaluation of dominant strictures, such as brush cytology, fluorescence in situ hybridization, and biopsies, which exhibit limited sensitivity for detecting CCA in PSC. We also review the role of advanced endoscopic approaches, including cholangioscopy, endoscopic ultrasound, and confocal endomicroscopy, alongside novel molecular diagnostics (next-generation sequencing and DNA methylation markers), metabolomics, bile microbiome, and radiomics, which show promise for risk stratification and CCA detection in PSC. Therapeutically, we review evidence supporting the use of balloon dilation as first-line therapy for the management of PSC strictures and discuss settings where plastic stents might be beneficial. Furthermore, we review the endoscopic management of other PSC complications, such as cholangitis, stones, acute cholecystitis, and posttransplant strictures. Finally, we provide best-practice recommendations to minimize the risk of complications, including the use of periprocedural antibiotic prophylaxis, technique modifications, and individualized sphincterotomy decisions. As innovative diagnostic and therapeutic strategies for PSC continue to evolve, rigorous multicenter, prospective studies are needed to assess the efficacy, safety, and cost-effectiveness of these strategies before widespread adoption.
Physical frailty is common in patients with cirrhosis and is strongly associated with health outcomes. While tools have been developed to assess frailty within administrative datasets, these instruments are neither speci...Physical frailty is common in patients with cirrhosis and is strongly associated with health outcomes. While tools have been developed to assess frailty within administrative datasets, these instruments are neither specific to patients with cirrhosis nor validated against established measures of physical frailty. Adult cirrhosis patients evaluated for liver transplantation with in-person frailty assessments using the Liver Frailty Index (LFI) were identified from a single center, 2017-2024. The electronic health record (EHR) was searched to identify ICD-10 codes associated with encounters in the 2 years prior to frailty assessment. Lasso regression was used to select ICD-10 codes associated with LFI and generate a Cirrhosis Administrative Frailty Index (CAFI). Model performance was assessed using discrimination (AUC) and calibration (CITL, slope). Competing risks regression was used to determine the association between CAFI and pre-transplant mortality (death or delisting due to illness), adjusting for MELD score. Among 2377 patients, 22% were frail by LFI>4.4. The CAFI includes 29 predictors, strongly associated with LFI>4.4, with an AUC of 0.73. In comparison, the Hospital Frailty Risk Score weakly discriminated LFI>4.4 (AUC=0.58). In multivariable models, each point increase in CAFI was associated with 29% increased risk of pre-transplant mortality (SHR=1.29, 95% CI: 1.11-1.50). We developed the CAFI, the first ICD-based frailty index specific to cirrhosis patients and validated against an in-person frailty measure. The CAFI will enable investigators to account for frailty as a confounder or mediator in administrative data-based studies, improving the validity of population-based research in patients with cirrhosis.
The role of immune checkpoint inhibitors (ICIs) before liver transplantation (LT) for HCC remains uncertain. In particular, the optimal treatment duration and the potential long-term oncologic benefits remain unclear. Th...The role of immune checkpoint inhibitors (ICIs) before liver transplantation (LT) for HCC remains uncertain. In particular, the optimal treatment duration and the potential long-term oncologic benefits remain unclear. Thus, we conducted a systematic review to evaluate outcomes of ICI as bridging or downstaging therapy before LT. Following PRISMA guidelines (PROSPERO CRD1082620), 5 databases were systematically searched up to March 2025. All published studies reporting ICI before LT in HCC were included. Data were synthesized descriptively, and exploratory regression models, including restricted cubic splines, were performed. Thirty-nine studies comprising 261 patients were included. Most were male (87.3%), over 50 years old, and had viral hepatitis as the predominant etiology of their liver disease. ICIs were mainly used for downstaging (84.2%), most frequently using nivolumab (24.5%). The median ICI duration was 63 days (42-105), with a median washout period of 57 days (29-116). Most patients presented with multifocal disease (77.9%) and tumors beyond Milan criteria, with a median largest lesion size of 37.5 mm (9.4-78.5). Macrovascular invasion was present in 15.7%. Posttransplant recurrence occurred in 18.6%. Shorter ICI exposure was significantly associated with a higher risk of recurrence (OR: 0.9; p <0.001). Spline models demonstrated that the benefit of ICI treatment was achieved at 80 days. Paradoxically, patients with BCLC A exhibited higher recurrence risk (OR: 5.2; p =0.01), perhaps underscoring the limitations of conventional staging in candidate selection. Allograft rejection occurred in 23.0% of patients and led to graft failure in 14.7%. Younger age (<50 y) and a shorter washout period (<50 d) were independently associated with an increased risk of recurrence and rejection, respectively. The duration of ICI treatment before LT is a critical factor influencing HCC recurrence risk, with an optimal treatment duration of more than 80 days. Furthermore, a confirmatory washout period of at least 50 days appears to be important to mitigate the risk of rejection.
Hazardous health behaviors increasingly contribute to end-stage liver diseases. To address surges in alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease, clinicians in hepatology...Hazardous health behaviors increasingly contribute to end-stage liver diseases. To address surges in alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease, clinicians in hepatology and liver transplantation must increasingly understand factors that influence eating and alcohol behaviors and consider ways to therapeutically influence patients' health choices. Stigma is a prominent influence on patient behavior, but is overused as a sweeping explanatory factor as to why difficulties arise, behavior change does not occur, or when outcomes are suboptimal. With more awareness of behavioral influences, clinicians may wonder if, for all its adverse effects, stigma exerts some therapeutic effects on patients considering altering habits. While stigma is less likely to yield desired outcomes, other co-occurring systemic, social, and interpersonal influences can favorably affect health choices (ie, structural nudging, social norms and consequences, and motivational interviewing, respectively). In this article, we analyze these related yet distinct constructs in ways pertinent to liver disease and transplantation, indicating where they might be applied and further studied.
Trezeguet Renatti G, Arrigone A, Costas C
… +22 more, Minetto J, Bosaleh A, de Davila MT, Aboud G, Degrave F, Cervio S, Reijenstein H, D'Arielli F, Jacobo Dillon A, Aredes D, Lauferman L, Malla I, Conde S, Chan D, Farall A, Riva N, Dip M, Casas S, Maluf D, Imventarza O, Halac E, Schaiquevich P
Surveillance biopsy is essential to detect graft rejection that remains silent to conventional liver function tests (LFTs), allowing tailored immunosuppression. The benefit of detecting subclinical biopsy-proven acute re...Surveillance biopsy is essential to detect graft rejection that remains silent to conventional liver function tests (LFTs), allowing tailored immunosuppression. The benefit of detecting subclinical biopsy-proven acute rejection (BPAR) comes at the cost of subjecting all pediatric recipients to an invasive procedure, including those who could potentially be safely spared if accurately identified as low risk of rejection using sensitive and noninvasive biomarkers of graft injury. We evaluated the ability of donor-derived cell-free DNA (dd-cfDNA) to rule out BPAR in pediatric liver transplant (LT) patients and its role in biopsy decision-making when used alongside LFTs. A clinical decision-making process combining LFTs and dd-cfDNA to identify low-risk rejection patients was developed using data from 98 patients under surveillance and 40 patients who underwent for-cause biopsy. Sixty BPAR events were recorded, and almost half of them (46.7%) were classified as subclinical BPAR (subBPAR). Only dd-cfDNA distinguished subBPAR from BPAR-free cases ( p =0.02), demonstrating a sensitivity of 96.7% (95% CI, 88.6-99.4) and a specificity of 34.6% (95% CI, 25.0-45.7) at a threshold of 1.9%. According to the decision-making process, patients with LFTs below the upper limit of normal and dd-cfDNA <1.9% would be spared from liver biopsy. Considering a BPAR prevalence of 43.4% in the study cohort, the negative and positive predictive values were 93.1% and 53.2%, respectively. In this large pediatric study, we demonstrate for the first time that low dd-cfDNA levels can reliably identify liver transplant patients at low risk of rejection, improving the tailoring of surveillance biopsies when used alongside LFTs.
Pulmonary function tests (PFTs) are performed ahead of listing for liver transplantation (LT) to assess respiratory fitness for transplantation. We aimed to establish whether pre-transplant PFTs were associated with post...Pulmonary function tests (PFTs) are performed ahead of listing for liver transplantation (LT) to assess respiratory fitness for transplantation. We aimed to establish whether pre-transplant PFTs were associated with post-LT overall survival and respiratory cause of death. A single-center retrospective study of patients transplanted between 2014 and 2023 was performed. Cox regression was used to analyze the relationship between PFT parameters, normalized for age, sex, ethnicity, and overall post-transplant survival. Competing risks regression was used to analyze the relationship between PFT parameters and respiratory death post-LT. Pre-transplant PFTs from 772 LT recipients were studied (33% female, median age 58 y, indication for transplant: alcohol-associated liver disease in 28.3%, metabolic dysfunction-associated steatotic liver disease in 18.0%). When combined with clinical variables, PFT parameters were predictive of post-transplant overall survival and respiratory death. Lower forced expiratory volume in 1 second (FEV1) (aHR 0.85, 95% CI 0.73-0.99, p =0.04), increased age at transplant (aHR 1.03, 95% CI 1.01-1.05, p =0.01), and current smoking at time of assessment (aHR 1.95, 95% CI 1.08-3.54, p =0.03) were independently associated with poorer post-transplant survival. Whereas both single-breath diffusing capacity of the lung (DLCO SB) (aSHR 0.66, 95% CI 0.52-0.82, p <0.001) and increasing age (aSHR 1.08, 95% CI 1.03-1.14, p =0.001) were independent predictors of post-LT respiratory cause of death. In conclusion, a lower FEV1 z -score was independently associated with poorer post-LT overall survival, and a lower DLCO SB z -score was associated with respiratory cause of death post-LT, supporting the routine use of PFTs in pre-liver transplant assessment.