Background: Posttransplant lymphoproliferative disorders (PTLDs) are a unique set of complications following solid organ and hematopoietic stem cell transplantation, predominantly originating from CD20 + B-cells. In pediatric recipients, the long-term prognosis warrants particular consideration. Methods: To enhance our understanding of PTLD in a large cohort, we performed a retrospective analysis of 2032 pediatric recipients who underwent liver transplantation (LT) between 2006 and 2019. Results: Among the 2032 individuals, 84 (4.13%) were diagnosed with PTLD. The cumulative incidence rates were 5.9% at 5 years and 7.7% at 10 years posttransplant. The median time to PTLD onset was 15.7 (4.9–24.3) months, with the majority (78.6%) of patients developing PTLD between 3 and 18 months post-LT. Notably, the peak occurrence of pediatric PTLD cases were observed between 3 and 6 months after transplantation. In a multivariable cox regression analysis, Epstein–Barr virus infection (hazard ratio [HR]: 9.4559; 95% confidence interval [CI]: 4.612–22.818; P < 0.001) and immunosuppression with tacrolimus (HR: 6.2101; 95% CI: 1.4715–31.3545; P = 0.0151) were identified as significant risk factors. The long-term graft survival rate for PTLD patients was 85.5%. Conclusions: PTLD is a significant concern for pediatric transplant recipients, potentially affecting their quality of life. Our study highlights the necessity for enhanced prevention strategies and prompts detection, particularly during periods of elevated incidence.

BACKGROUND:The adoption of technical variant grafts has expanded the donor pool for pediatric liver transplantation, but it also poses a risk of portal vein thrombosis (PVT). This study evaluated risk and prognostic factors of PVT in children undergoing liver transplantation with technical variant grafts. METHODS:A total of 3137 pediatric patients from 19 centers were included: 470 received split/reduced deceased donor grafts and 2667 received living donor grafts. Multivariable logistic regression was used to identify risk factors, whereas time-dependent Cox models were used to assess the impact on survival. RESULTS:PVT occurred in 102 patients (3.3%) and was associated with increased mortality (adjusted hazard ratio, 2.86; 95% confidence interval [CI], 1.13-7.25; P  = 0.027) and graft loss (adjusted hazard ratio, 9.97; 95% CI, 4.90-20.3; P  < 0.001). Risk factors included younger age, lower weight, higher Pediatric End-Stage Liver Disease score, longer cold ischemia and operation times, higher graft-to-recipient weight ratio, increased red blood cell transfusions, and biliary atresia. After adjusting for center, lower weight (odds ratio, 0.84 per kg; 95% CI, 0.71-1.00; P  = 0.047) and biliary atresia (odds ratio, 2.34; 95% CI, 1.10-5.00; P  = 0.027) remained predictors. Five-year patient (88.4% versus 93.1%) and graft survival (82.7% versus 96.3%) were significantly inferior in patients with PVT. CONCLUSIONS:Low-weight children with biliary atresia constituted a high-risk group, highlighting the necessity for early detection and management.

The prognosis for patients diagnosed with hepatocellular carcinoma with bile duct tumor thrombus (HCC-BDTT) remains dismal, and there are presently no universally accepted treatment guidelines to address this complex condition. Long-term outcomes of liver transplantation (LT) for HCC-BDTT patients are unclear, and whether LT is a proper therapeutic option for HCC-BDTT patients remains to be determined. Therefore, we design a clinical trial to evaluate whether LT can improve recurrence-free survival (RFS) and overall survival (OS) in HCC-BDTT patients. This is an open-labeled, single-arm, prospective, multicenter and real-world study aiming to assess the survival outcomes of HCC-BDTT patients in LT. Patients will be enrolled based on histological confirmation of HCC with BDTT. The study is planned to take 4 years, 2 years for enrollment and 2 years for follow-up. We anticipate that LT confers beneficial survival outcomes for HCC-BDTT patients, specifically in terms of the pivotal parameters, such as RFS and quality of life. Upon successful completion of the trial, we will extend our monitoring over a longer follow-up time to accurately estimate important indicators such as OS. We expect that this study provides substantial evidence to refine treatment guidelines through thorough data analysis, ultimately contributing to better patient outcomes and advancing our understanding of the disease.Trial Register: Trial registered at www.clinicaltrials.gov (NCT06928415)

BACKGROUND & AIMS:We investigated the association between subtypes of steatotic liver disease (SLD) and 23 site-specific cancers in a nationwide cohort of young Korean adults. METHODS:From a nationwide health screening database in Korea, 2,877,245 young adults 20-39 years of age between 2013 and 2014 were included and followed up until December 31, 2022. Individuals were categorized into non-SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) groups. Hepatic steatosis was defined as a fatty liver index ≥30. The primary outcome was all cancers, while secondary outcomes included 23 site-specific cancers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). RESULTS:During 22,819,681 person-years of follow-up, 46,729 incident cancer cases developed. The MASLD (HR, 1.19; 95% confidence interval [CI], 1.16-1.22; P < .001) MetALD (HR, 1.12; 95% CI, 1.07-1.18; P < .001), and ALD (HR, 1.21; 95% CI, 1.12-1.31; P < .001) groups had a higher risk of all cancers compared with the non-SLD group. Most obesity-related cancers showed increased risk in individuals with either MASLD or MetALD. There was an increasing trend in all-cancer risk with increasing number of cardiometabolic risk factors among MASLD. Alcohol consumption had a modest effect on overall cancer risk, with varying effects on specific cancer types. CONCLUSIONS:Young adults with MASLD, MetALD, or ALD are at increased risk of developing early-onset cancer.

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that can occur after solid organ transplantation but remains underrecognized in this setting. The diagnosis is often delayed due to overlapping clinical manifestations with infection, rejection, or malignancy, and management becomes particularly challenging when accompanied by severe hepatic dysfunction. Here, we describe a pediatric patient who developed Epstein–Barr virus (EBV)–associated secondary HLH following liver re‐transplantation for biliary atresia. On postoperative Day 10, the patient presented with high fever, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and marked hyperferritinemia, accompanied by rapidly worsening liver injury. Bone marrow biopsy confirmed hemophagocytosis. Given the severe hepatic impairment and persistent inflammation, the patient received three doses of emapalumab (1 mg/kg), a monoclonal antibody blocking interferon‐γ, combined with corticosteroids, intravenous immunoglobulin, and antimicrobial prophylaxis. The treatment led to a rapid decline in ferritin levels, reversal of liver dysfunction, and complete clinical recovery without opportunistic infections. The patient has remained stable with normal liver function and negative EBV DNA for over 2 years of follow‐up. This case demonstrates that early interferon‐γ blockade can safely and effectively reverse HLH‐related liver injury after transplantation, offering a promising therapeutic strategy for the management of secondary HLH complicated by severe hepatic dysfunction.

The relationship between the newly proposed steatotic liver disease (SLD) subtypes—metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic alcohol-associated liver disease (MetALD)—and dementia is understudied. We evaluated the dementia risk associated with these subtypes. This retrospective cohort study included 296,001 participants aged over 60 who underwent health examinations between 2009 and 2010. Participants were categorized into non-SLD (reference), MASLD, and MetALD groups and followed up until dementia onset, death, or December 31, 2019. SLD was defined by a fatty liver index ≥ 30, with (i) MASLD based on cardiometabolic risk factors, and (ii) MetALD as MASLD with moderate alcohol intake. Outcomes included overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Subdistribution hazard ratios (SHRs) was calculated using the Fine–Gray model, treating death as a competing risk. Over 7,430,253 person-years of follow-up, 11,345 dementia cases occurred (10,863 AD and 2,159 VaD). Adjusted SHRs for MASLD were 1.10 (1.07–1.13) for AD and 1.20 (1.13–1.27) for VaD. For MetALD, SHRs were 0.90 (0.87–0.94) for AD and 1.53 (1.40–1.66) for VaD. Dementia risk in both MASLD and MetALD increased over longer periods, with MetALD initially linked to increased VaD risk and decreased AD risk, which reversed after three years. MASLD and MetALD were associated with increased risks of AD and VaD; MetALD showing a stronger association with VaD. Understanding the distinct effects of different SLD subtypes on dementia is crucial for improving risk assessment and management strategies.

Potential conflict of interest: Nothing to report. Funding was provided by the National Natural Science Foundation of China (81902379) and the National Key Research on Precision Medicine of China (2017YFC0908102, 2018ZX10723204). TO THE EDITOR: We read with great interest the article by Bhangui et al.(1) regarding the application of expanded selection criteria for living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). The authors incorporated alpha‐fetoprotein (AFP) and tumor [18F]fludeoxyglucose ([18F]FDG) positron emission tomography (PET) avidity into the selection criteria and evaluated a total of 405 patients who underwent LDLT for HCC irrespective of tumor size and number. Surprisingly, more than half of the patients beyond Milan criteria had a 5‐year recurrence‐free survival (RFS) as high as 70%. The overall survival excluding postoperative deaths was more than 60% as well. The results are encouraging for patients suffering from HCC beyond conventional selection criteria and may expand the donor pool by using living donor grafts. The authors also analyzed different variables predicting HCC recurrence. Pre–liver transplantation (LT) AFP ≥100 ng/mL, tumor burden beyond the University College of San Francisco (UCSF) criteria, and [18F]FDG PET avidity were correlated with worse RFS. In combination of the risk predictors, a prognostic model stratifying patients into 3 risk groups was developed. Based on these findings, the authors concluded that expanded selection criteria incorporating tumor biology could achieve acceptable long‐term outcomes. We appreciate the well‐designed research that expands the LDLT criteria for HCC. However, the authors' suggestion needs further discussion and interpretation. First, pretransplant locoregional therapy (LRT) that induces tumor necrosis and reduces dissemination is acknowledged as one of the independent factors influencing recurrence and overall survival.(2) However, neither survival difference nor prognostic analysis was reported in patients receiving LRT. Potential benefits provided by the treatment may cause bias in evaluating long‐term outcomes. Second, accumulating evidence has shown that the response to LRT is a surrogate marker of tumor biological behavior and determines the prognosis.(3) In the present study, pre‐LT AFP level and [18F]FDG PET avidity were included as selection criteria. However, the radiological and AFP response to pretransplant therapy is lacking, which impedes the accurate assessment of tumor behavior. The subgroup of patients receiving LRT should be further evaluated in detail. Another important issue is related to posttransplant adjuvant therapy, which plays an important role in prolonging patients' survival. Oral multikinase inhibitors such as sorafenib and lenvatinib have been approved as adjuvant therapies for unresectable HCC. The value of oral multikinase inhibitors in reducing recurrence and treating HCC after LT has also been confirmed by several studies.(4) In addition, a combination of sorafenib and a mammalian target of rapamycin inhibitor exerts a joint effect in inhibiting tumor growth.(5) However, the limited data on postoperative anticancer treatment were revealed in the present study. Therefore, future studies should focus on posttransplant adjuvant therapy to confirm its effect in LDLT for HCC. In conclusion, the study demonstrates that LDLT may provide an outstanding potential for patients with HCC. The recommendation of patients with expanded criteria still needs further exploration in larger prospective studies with careful evaluations of both pretransplant and posttransplant anticancer therapies. We believe that LDLT could expand the donor pool and provide a favorable prognosis through the careful selection of patients.

Background Cytomegalovirus infection is one of the most common complications after solid organ transplantation. There have been several classes of antiviral drugs for the prevention of cytomegalovirus infection, such as acyclovir, valacyclovir, ganciclovir and valganciclovir. Methods We searched relevant prospective and multi-armed studies on PubMed from Jan. 1984 up to Mar. 2018. Results Seventeen prospective studies involving 2062 patients were included in the analysis. In the case of cytomegalovirus infection, the ganciclovir group (OR = 0.24, 95% CI 0.09–0.57) and the valacyclovir group (OR = 0.20, 95% CI 0.04–0.69) provided significantly better outcomes than the control group. The ganciclovir (OR = 0.37, 95% CI 0.13–0.86) and valacyclovir groups (OR = 0.31, 95% CI 0.07–0.98) showed moderate superiority compared to the acyclovir group. As for cytomegalovirus disease, the ganciclovir, valacyclovir and valganciclovir groups showed significant advantages compared with the control group (ganciclovir group: OR = 0.17, 95% CI 0.07–0.31, valacyclovir group: OR = 0.08, 95% CI 0.01–0.33, valganciclovir group: OR = 0.14, 95% CI 0.02–0.45). Similarly, the ganciclovir group (OR = 0.38, 95% CI 0.12–0.71) and the valacyclovir group (OR = 0.17, 95% CI 0.03–0.72) showed better results than the acyclovir group. Conclusion Valacyclovir showed to be the most efficient antiviral for the prevention of cytomegalovirus infection and disease. Additional studies are required to evaluate putative side effects associated with valacyclovir administration.