Search Results (2,564)

Background: ABO-incompatible living-donor liver transplantation (ABOi LDLT) can expand the donor pool for patients with hepatocellular carcinoma (HCC), but concerns remain regarding tumor recurrence and long-term survival. Methods: A systematic review and meta-analysis was performed according to PRISMA 2020. PubMed, Embase, and Web of Science were searched. Comparative studies evaluating oncologic outcomes after ABOi versus ABO-compatible (ABOc) LDLT for HCC were included in the quantitative synthesis; non-comparative studies were included in the qualitative synthesis. Hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using a random-effects model. When HRs were not directly reported, they were estimated from Kaplan–Meier curves using established methods. Results: Sixteen reports were screened, 12 full-text articles were assessed, and 8 studies were included in the systematic review. Three comparative single-center cohort studies were eligible for meta-analysis. Pooled analysis showed no significant difference between ABOi and ABOc LDLT for RFS (HR 1.07, 95% confidence interval [CI] 0.77–1.49; I² = 0%) or OS (HR 1.08, 95% CI 0.74–1.57; I² = 0%). Five additional studies were synthesized qualitatively, suggesting that recurrence risk may be influenced more by tumor biology and peri-transplant management, including desensitization intensity and immunosuppression exposure, than by ABO incompatibility itself. Conclusions: Current limited comparative evidence does not demonstrate inferior RFS or OS after ABOi LDLT in carefully selected patients with HCC. Larger multicenter comparative studies with standardized reporting of tumor biology, desensitization protocols, and immunosuppression exposure are warranted to confirm these findings and clarify protocol-related effects on post-transplant recurrence. Full article

Background/Objectives: Hepatitis B core-related antigen (HBcrAg) is a surrogate marker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA). However, the impact of switching nucleos(t)ide analogs on HBcrAg levels remains unclear. The current study evaluated changes in HBcrAg levels following a switch from entecavir (ETV) to tenofovir alafenamide (TAF) compared with continued ETV therapy. Methods: This retrospective study included patients with chronic hepatitis B who either switched from ETV to TAF between 2017 and 2022 (ETV–TAF group) or continued ETV therapy during the same period (ETV group). HBcrAg levels were measured annually, and longitudinal changes over 3 years were analyzed based on an index year defined for each patient. Propensity score matching for age, sex, HBcrAg levels, liver transplantation status, and ETV treatment duration yielded 10 patients per group. Results: Baseline characteristics were well balanced after matching. HBV DNA and HBsAg levels remained suppressed in both groups throughout follow-up. The ETV-TAF group showed greater declines in HBcrAg than the ETV group at year 2 (−0.20 vs. −0.10 log U/mL, p = 0.007) and year 3 (−0.30 vs. −0.10 log U/mL, p = 0.006). No virological breakthroughs occurred. Conclusions: Switching from ETV to TAF was associated with greater reductions in HBcrAg levels over 3 years than continued ETV therapy, even in patients with suppressed HBV DNA. These findings suggest that switching to TAF may be associated with further suppression of viral transcriptional activity reflected by HBcrAg reduction and support its potential clinical utility for achieving deeper viral suppression. Full article

Background/Objectives: Acute kidney injury (AKI) is a common complication after liver transplantation. Although intraoperative hypotension has been associated with its development, the impact of shock persistence and its hemodynamic profile remains poorly defined. Methods: This was a single-center retrospective observational study including 226 adult patients undergoing liver transplantation. Intraoperative shock was defined as a mean arterial pressure < 60 mmHg or a ≥30% decrease from baseline and was classified as hypovolemic, distributive, cardiogenic, or mixed based on pulmonary artery catheter data. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria within the first 7 postoperative days. Associations were assessed using adjusted logistic regression models. Results: Intraoperative shock occurred in 35.8% of patients, and the incidence of AKI was 52.2%. The presence of shock was not independently associated with AKI (adjusted OR 1.66; 95% CI 0.94–2.95). However, shock occurring in multiple phases of the procedure was associated with a higher incidence of AKI (81.8% vs. 50%; p = 0.010), greater severity, and higher mortality (27.3% vs. 3.4%; p = 0.002). In exploratory analyses, mixed shock was associated with an increased need for renal replacement therapy within 30 days (p = 0.006), persistent renal dysfunction at day 30 (p = 0.048), and higher mortality (p = 0.01), while hypovolemic shock was associated with moderate AKI (OR 6.60; p = 0.011). Conclusions: The presence of intraoperative shock alone is not independently associated with AKI. In contrast, its persistence is strongly associated with AKI development and worse clinical outcomes. Full article

Background/Objectives: Frailty is a validated predictor of waitlist mortality and perioperative risk in liver transplant candidates, but its association with early post-transplant outcomes in large real-world cohorts remains incompletely characterized. This study evaluated the association between administratively defined pre-transplant frailty and early clinical outcomes following liver transplantation. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network. Adults undergoing first-time isolated liver transplantation through February 2026 were included. Frailty was identified using ICD-10-CM codes for frailty, sarcopenia, cachexia, weakness, abnormal gait/mobility, or reduced mobility documented within 12 months before transplantation; patients coded only for nonspecific weakness were excluded from the frailty cohort. Patients underwent 1:1 propensity score matching using 18 baseline covariates, including demographics, comorbidities, laboratory values, albumin, and MELD-Na. The primary outcome was all-cause mortality at 7, 30, and 90 days. Secondary outcomes included acute kidney injury, prolonged mechanical ventilation, vasopressor requirement/hemodynamic instability, renal replacement therapy, ICU and hospital length of stay, and 90-day readmission. Sensitivity analyses used a restrictive ≥ 2-code frailty definition and substituted MELD 3.0 for MELD-Na in the propensity model. Results: Among 4860 eligible recipients, 742 had administratively defined frailty and 4118 did not. After matching, 730 patients remained in each group with well-balanced covariates. Administratively defined frailty was associated with higher mortality at 7, 30, and 90 days, with numerically smaller relative risks at later time points. It was also associated with higher risks of acute kidney injury, prolonged mechanical ventilation, vasopressor requirement/hemodynamic instability, renal replacement therapy, longer ICU and hospital stays, and 90-day readmission. Findings were directionally consistent in both sensitivity analyses. Etiology-stratified analyses were exploratory and showed no statistically significant heterogeneity across liver disease etiologies. Conclusions: In this large propensity-matched multicenter cohort, administratively defined pre-transplant frailty was associated with worse early outcomes after liver transplantation. Because frailty and several outcomes were identified using structured EHR and administrative data, findings should be interpreted as associative and hypothesis-generating. Prospective studies using validated frailty instruments and granular donor, intraoperative, and center-level variables are needed to confirm these findings. Full article

Background/Objectives: Survival rates after pediatric liver transplantation have improved substantially over recent decades, yet the psychiatric consequences for recipients remain a concern that warrants closer attention. We sought to map the psychiatric symptom burden across multiple domains in this population and to determine which symptom clusters carry the greatest impact on health-related quality of life (HRQOL). Materials and Methods: Fifty liver transplant recipients between the ages of 8 and 18 were enrolled at a single center. Children and their parents completed four psychiatric measures—the CBCL, CDI, SCARED, and CRIES-13—alongside the parent-proxy PedsQL to capture HRQOL across physical, emotional, social, and school functioning domains. Correlations between instruments were calculated, and linear regression was used to determine which psychiatric variables independently predicted PedsQL Total scores. Results: Across all psychiatric measures, higher symptom scores were associated with lower HRQOL, with school functioning recording the lowest absolute PedsQL domain score, while emotional functioning demonstrated the strongest and most consistent inverse correlations with all psychiatric symptom measures across instruments. CBCL Total (r = −0.607), SCARED Total (r = −0.557), and CRIES-13 Total (r = −0.548) scores all correlated meaningfully with overall HRQOL. When entered into multivariable analysis, anxiety symptoms measured by the SCARED (β = −0.295, p = 0.032) and post-traumatic stress symptoms measured by the CRIES-13 (β = −0.400, p = 0.004) stood out as the two independent predictors of worse PedsQL Total scores. Conclusions: Even in medically stable recipients, anxiety and post-traumatic stress symptoms were independently associated with lower daily functioning scores and overall quality of life. These findings suggest that routine psychosocial screening and trauma-informed approaches may warrant integration into post-transplant care protocols, and that prospective, adequately powered studies are needed to confirm and extend these associations. Full article

Acute-on-chronic liver failure (ACLF) is the point at which cirrhosis stops behaving as a chronic liver disease and becomes a rapidly destabilising systemic illness. It is the real tipping point in advanced liver disease: the moment when limited hepatic reserve is no longer the only issue, and the clinical picture is instead defined by systemic inflammation, extrahepatic organ dysfunction, and a high risk of short-term death. This has changed how we understand the natural history of cirrhosis. Rather than a simple linear progression toward liver failure, advanced chronic liver disease is now better seen as a dynamic continuum that may lead to first decompensation, recurrent decompensation, ACLF, end-stage disease, or, in selected cases, recompensation if the underlying driver is effectively controlled. This shift matters because patients with ACLF are not simply “sicker cirrhotics”. They are in a distinct pathophysiological state, marked by inflammation, circulatory dysfunction, immune dysregulation, and organ cross-talk that extends beyond the liver. In this setting, the boundaries between liver failure, sepsis, renal dysfunction, and critical illness become blurred, which is why ACLF remains such a difficult syndrome to manage. At the same time, recent guidance has improved the approach to decompensated cirrhosis, HRS-AKI, infection, transplantation, and palliative care, while newer consensus efforts have tried to reduce differences between ACLF definitions. In practice, management still depends on simple but disciplined principles: early recognition, rapid identification of precipitants, parallel organ support, prompt treatment of infection and HRS-AKI, repeated reassessment, and urgent transplant evaluation when appropriate. This review examines ACLF and end-stage liver disease as interconnected stages of advanced cirrhosis and discusses how care can be both aggressive when recovery is possible and humane when recovery is not. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality, with incidence expected to increase. Liver transplantation is the most definitive curative option for early HCC, but many patients present beyond accepted transplant criteria, including the Milan criteria. Downstaging aims to reduce tumor burden and enable transplantation without compromising long-term outcomes. Methods: We reviewed the literature on liver transplantation, immune checkpoint inhibitors, immunotherapy–locoregional therapy combinations, and immune-related adverse events in HCC. Results: Immunotherapy-based strategies are emerging as downstaging approaches in selected patients. In advanced HCC, immune checkpoint inhibitor combinations have improved objective response rates compared with tyrosine kinase inhibitors, reaching approximately 20–36% in pivotal phase III trials. In the downstaging setting, early data suggest that immune checkpoint inhibitors, particularly with locoregional therapies, can achieve sufficient tumor regression to permit transplantation in patients initially beyond criteria. The ImmunoXXL trial reported successful downstaging and transplantation in all 16 patients treated with atezolizumab–bevacizumab, with 62.5% complete pathological responses, 2-year recurrence-free survival of 90%, and overall survival of 94%. The VITALITY study achieved successful downstaging in 75.6% of patients beyond Milan criteria, with 36.7% undergoing transplantation and 3-year post-transplant survival of 85%. However, pre-transplant immune checkpoint inhibitor exposure carries a clinically relevant risk of acute allograft rejection, reported in approximately 16–28% of transplanted patients. Conclusions: Immunotherapy-based downstaging before liver transplantation is promising but remains non-standard. Its use should be restricted to carefully selected patients within multidisciplinary protocols, as evidence remains limited by small cohorts, heterogeneous regimens, uncertain washout intervals, and rejection risk. Full article

Background: Parents of children undergoing liver transplantation face substantial caregiving demands that may adversely affect their mental health across multiple domains. Systematic evaluation of psychosocial outcomes in this population remains limited, particularly in settings that include immigrant families. Method: This was a single-center, cross-sectional study including the parents of 50 children after liver transplantation. Major sociodemographic variables included parental age, sex, education, chronic disease, and immigration status. We also recorded children’s demographics, transplant-related data, follow-up findings, and mental health status. Instruments for psychiatric assessment included the Generalized Anxiety Disorder 7-item scale (GAD-7; anxiety), Patient Health Questionnaire-9 (PHQ-9; depression), Perceived Stress Scale-10 (PSS-10; stress), and Pittsburgh Sleep Quality Index (PSQI; sleep quality). Results: We enrolled 50 parents of 50 pediatric liver transplant recipients (43 Turkish citizens, 7 Syrian immigrants; 28 fathers, 22 mothers; mean age: 40.10 ± 6.65). Time since transplantation showed weak negative correlation with PHQ-9 and GAD-7. Stress (PSS) levels had weak to strong positive correlation with PSQI, PHQ-9, and GAD-7. Sleep quality (PSQI) was positively correlated with PHQ-9 and GAD-7. Depressive findings (PHQ-9) were strongly and positively correlated with GAD-7. In Firth-penalized multivariable models, high PHQ-9 scores were independently associated with shorter time since transplantation (p = 0.001) and high PSS (p = 0.003). High GAD-7 scores were independently associated with shorter time since transplantation (p = 0.025) and high PSS (p = 0.001). Conclusions: The parents of pediatric liver transplant recipients experience high levels of stress, sleep issues, depression, and anxiety, which demonstrate multiple correlations. Full article

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios. Full article

Background/Objectives: Hepatitis B virus (HBV) transmission risk from donors with resolved HBV infection remains a concern in kidney transplantation, because covalently closed circular deoxyribonucleic acid (DNA) may persist despite serological recovery. In this study, we evaluated the transmission risk from anti-hepatitis B core antibody (anti-HBc)-positive, hepatitis B surface antigen (HBsAg)-negative, and HBV-DNA-negative living donors to anti-HBc-negative recipients. Methods: We retrospectively reviewed living-donor kidney transplantations performed at our institution (June 2011–December 2024). Among 277 transplantations, 26 met the inclusion criteria. All recipients had received HBV vaccination prior to transplantation. Serological markers, including HBsAg, anti-HBc, anti-hepatitis B surface antibody (anti-HBs), and HBV-DNA, were monitored before and after transplantation. Results: Five recipients (19.2%) achieved anti-HBs seroconversion after vaccination pre-transplantation, but all lost protective antibody levels before or shortly after transplantation. Five recipients (19.2%) showed transient post-transplantation anti-HBs positivity; three cases were considered vaccine-related, and two were possibly transplant-related. None of the patients developed liver enzyme elevation, clinical hepatitis, HBsAg positivity, or anti-HBc seroconversion. Among the four recipients tested for HBV-DNA, all results remained undetectable throughout follow-up. None of the recipients maintained protective anti-HBs levels pre- or post-transplantation, despite universal vaccination. Two recipients (7.7%) developed delayed anti-HBs positivity without anti-HBc seroconversion, HBsAg positivity, or detectable HBV-DNA, suggesting possible subclinical HBV antigen exposure from the allograft. Conclusions: Kidney transplantation from donors with resolved HBV infection was not associated with clinically evident HBV infection, although transient serological changes were observed. Optimized vaccination strategies and structured post-transplant monitoring may enhance the safety of transplantations involving such donors. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

The concept of “fever burden” represents a quantitative and dynamic expression of the host immunometabolic response, integrating the duration, intensity, and temporal characteristics of postoperative temperature alterations. This review discusses the biological rationale underlying postoperative fever and explores its potential clinical relevance in the context of liver surgery, particularly in distinguishing infectious complications from sterile postoperative inflammation. This narrative review was based on a structured literature search of PubMed and Embase (2000–2025) to identify clinical and translational studies addressing postoperative fever after hepatic resection and liver transplantation. The retrieved literature was narratively synthesized with emphasis on fever burden, temperature trajectories, and biologically plausible mechanisms potentially associated with postoperative recovery and infectious complications. Current evidence suggests that postoperative fever may reflect dynamic activation of innate immune and inflammatory pathways rather than representing a purely binary sign of infection. In liver surgery, clinically relevant information may be better captured by temporal fever characteristics, including timing of fever onset, peak temperature, and recurrent febrile episodes, than by isolated temperature measurements alone. However, direct liver-surgery-specific evidence remains limited, and broader concepts related to temperature trajectories and immunometabolic phenotyping should currently be regarded as hypothesis-generating. Fever burden and temperature trajectory analysis may therefore represent promising conceptual approaches for interpreting postoperative host-response patterns after liver surgery, although their diagnostic and prognostic value requires prospective validation in liver-specific clinical cohorts. Full article

Chronic liver disease remains a major global health burden, with liver transplantation as the only definitive therapy despite severe limitations in donor availability, surgical morbidity, and patient eligibility. Although the liver has substantial intrinsic regenerative capacity, endogenous repair is often insufficient in chronic injury, cirrhosis, and acute-on-chronic liver failure. As a result, regenerative strategies that restore liver function without whole-organ replacement are increasingly pursued. This review examines controlled release biomaterial-based liver regeneration platforms, particularly those that utilize hydrogels and/or complementary nanoparticle systems, as clinically practical tools to enhance endogenous regeneration. We include discussion of both 3D scaffold-based and injectable hydrogels to enhance regeneration. Used as biological support and controlled release mixtures, they enable local retention, entrapping and controlling the release of regenerative cues including growth factors (HGF, EGF, etc.), nucleic acids for gene expression, stem cells or other cell populations, and conditioned extracellular vesicles, overcoming poor cell engraftment, short cytokine half-lives, and other limitations. Further, synthetic nanoparticles can structure release at the protein/molecular level as well as catalytically modulating oxidative stress and inflammation. Within the context of these systems, we structure the anatomical, engineering, and imaging considerations essential for the clinical translation of gel composite systems while highlighting remaining barriers to wider clinical adoption. Collectively, these advances position biomaterial-enabled regenerative therapies as a realistic alternative or bridge to donor restricted liver transplantation. Full article

Purpose: Simultaneous liver–kidney transplantation (SLK) eligible candidates may receive SLK or liver-alone transplant (LA) with access to kidney transplant after initial LA (KAL). We aimed to characterize SLK-eligible recipient outcomes according to treatment approach. Methods: This study utilized 2017–2023 SRTR data to identify SLK-eligible deceased donor liver transplants. Recipients were placed into two groups based on whether SLK was performed; non-SLK patients were sub-stratified into LA and KAL cohorts. After baseline comparisons, 2-year patient and graft survival outcomes were characterized by univariable and multivariable Cox proportional hazard regression and Kaplan–Meier analysis. Results: Among 4879 candidates identified, 3746 (76.8%) underwent SLK, 1023 (21.0%) LA, and 110 (2.3%) KAL. SLK recipients maintained the highest eGFRs at 6 months, 1 year, and 2 years post-transplant (p < 0.01). Compared to SLK recipients, non-SLK recipients had a higher 2-year risk of mortality (aHR 2.46, p < 0.01), all-cause events (aHR 1.91, p < 0.01), and liver graft failure (HR 1.55, p = 0.02). LA conferred a higher 2-year mortality risk (aHR 2.98, p < 0.01) and all-cause event risk (aHR 2.25, p < 0.01), while KAL had comparable mortality risk to SLK (aHR 0.43, p = 0.40). Conclusions: When SLK-eligible candidates undergo transplants, SLK remains the optimal path forward, even when a safety net kidney can be performed. Full article

Background/Objectives: Regional adipose tissue has been studied as a prognostic factor in various extra-hepatic diseases, but data in the setting of cirrhosis is scarce. Our aim was to evaluate the association of regional adipose tissue indices with the severity of liver disease and its impact on the outcome of patients with cirrhosis. Methods: Three hundred and thirty-seven patients with cirrhosis were prospectively enrolled in the study. Clinical and laboratory data were recorded, and MELD-Na and Child-Turcotte-Pugh scores were calculated. Physical performance was evaluated with handgrip strength, the Short Physical Performance Battery test, and the Liver Frailty Index. Dual-energy X-ray absorptiometry was used for the evaluation of total and regional lean and fat mass. Results: A low trunk fat percentage was found to be independently associated with a MELD-Na score ≥ 15 (Odds Ratio: 0.92, p = 0.007). MELD-Na score and trunk fat percentage were the only factors independently associated with mortality [Hazard Ratio (HR): 1.078, p = 0.02 and HR: 0.95, p = 0.03, respectively], while a separate analysis based on gender confirmed this finding only in men. In the total cohort, patients with a trunk fat percentage < 27.5% had worse outcomes (log-rank 11.4; p < 0.001). Conclusions: This study marks the first effort to examine the association of indices related to regional adipose tissue distribution with the severity of liver disease and outcome. Trunk fat percentage was the only body composition parameter independently associated with advanced liver disease and prognosis in the total cohort specifically in men, but not in women. Further studies are needed to validate the predictive role of adipose tissue in patients with cirrhosis. Full article