Background: Living donor liver transplantation (LDLT) is the predominant transplantation technique in regions with low rates of deceased donation. Right-lobe grafting is adopted in most clinical and radiological donor/recipient scenarios. Due to the considerable variations in right-lobe hepatic venous anatomy, many techniques have been used over the years for the purpose of appropriate venous outflow reconstruction during the recipient procedure. In this paper, we present the technical details and consequences of a complex venous outflow reconstruction model (CORM) based on experience, and the long-term patency results obtained using the model. Methods: Data of patients with end-stage liver disease who underwent LDLT between 21 December 2017 and 29 November 2022 were prospectively collected and retrospectively reviewed. The nomenclature of CORM was assigned when three or more hepatic vein anastomoses were performed. Patients with CORM (CORM group; n = 69) were compared with non-CORM patients (non-CORM group; n = 130) in terms of demographic, pre- and postoperative clinical, and follow-up features. Results: Sixty-nine recipients had three or more separate outflow reconstructions (RHV, RIHV, and one or more anterior sectoral veins); these constituted the CORM group. The estimated graft volume of the CORM group was significantly lower than that of the non-CORM group (833 vs. 898; p = 0.022), and the mean GRWR was also significantly lower (1.1 vs. 1.2; p = 0.004). CORM cases showed longer anhepatic phases, as well as longer times for cold and warm ischemia, than non-CORM cases (63 vs. 51 min, 46 vs. 38 min, and 48 vs. 33 min, p < 0.001), though no difference was found with respect to total operative duration. There were no statistical differences between the two groups with respect to rates of in-hospital re-exploration, length of ICU stay, or length of total hospital stay. Graft survival rates at 1 year, 3 years, and 5 years were 88.1%, 83.3%, and 83.3%, respectively, in the CORM group, and 82.9%, 80.2%, and 70.6%, respectively, in the non-CORM group (p = 0.167). Conclusions: Performing three or more CORMs in right-lobe LDLT is not associated with inferior outcomes, either with regard to perioperative variables or to patient and graft outcomes. Right-lobe graft with complex venous anatomy from a living donor should not be a determinant factor for donor exclusion.

Split liver transplantation (SLT) from deceased donors is a potential solution to the global organ shortage. While effective in patients with mild disease, outcomes in high MELD score recipients remain uncertain and conflicting. This study compares survival in high vs. low MELD score recipients.

This retrospective single-centre study included all consecutive patients transplanted with a split liver graft between 2010 and 2022. Two groups of recipients with MELD<25 and ≥ 25 at LT were compared.

The study population included 119 patients (n = 98 with MELD<25, n = 21 with MELD≥25) with an average follow-up of 55 months. Both groups were comparable in terms of indication for transplantation and donor characteristics. The high MELD group required more blood transfusions (7 vs. 3 units; p < 0.001) during LT and had a longer stay in intensive care unit (7 vs. 5 days; p = 0.011). Biliary, arterial, and venous complications were similar between groups, as well as graft survival (5 years: 75 % vs. 61 %, p = 0.35) and long-term overall survival (5 years: 83 % vs. 75 %, p = 0.17).

Our results indicate that SLT for patients with MELD≥25 improves access to grafts, is feasible and safe, without significant increased risk of severe complications or decreased long-term overall patient or graft survivals.

Liver transplantation (LT) is a well-established therapy for patients with decompensated cirrhosis and early-stage hepatocellular carcinoma. Liver transplantation activity varies sharply across Latin American (LATAM) countries due to differences in resources, expertise, and funding and local attitudes toward organ donation and transplantation. This current guidance of postoperative care after LT is the first position paper of the Latin American Association for the Study of the Liver (ALEH) Special Interest Group (SIG), drawing evidence-based recommendations regarding immediate and long-term postoperative care of LT recipients, taking into consideration their applicability in Latin America.

This study aimed to evaluate the mediating role of healthy life awareness in the relationship between the sociodemographic characteristics and psychological well-being of liver transplant patients. The sample of the study consisted of 202 patients aged between 18 and 69 years who underwent liver transplantation surgery at a hospital in Turkey. The data were collected using a sociodemographic information form, the "Healthy Life Awareness Scale" and the "Psychological Well-Being Scale." Healthy life awareness directly predicted psychological well-being (β: 0.68, p < 0.01). Education positively predicted psychological well-being both directly (β: 0.14, p < 0.05) and indirectly through healthy life awareness (β: 0.76, p < 0.05). Age indirectly predicted healthy life awareness and psychological well-being through employment status and education. The income level positively predicted healthy life awareness (β: 0.14, p < 0.05), whereas gender (male) negatively predicted healthy life awareness (β: -0.22, p < 0.01). Healthy life awareness was a significant predictor of psychological well-being. The results of this study may offer valuable information for healthcare providers to tailor interventions that also support mental and emotional health, which is critical to the long-term success of transplant outcomes.

Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion. However, it remains unclear whether MSCs isolated from chronically inflamed livers are similar in their basic cellular properties to MSCs obtained from healthy livers. We applied a large array of tests to compare resident MSCs isolated from apparently normal liver tissue and from chronically inflamed livers of patients with fibrosis, cirrhosis, and viral hepatitis. Chronic inflammatory environment did not alter the major cellular characteristics of MSCs, including the expression of MSC markers, stem cell markers, adhesion molecules, and the hallmarks of senescence, as well as cell proliferation, migration, and secretome. Only the expression of some immune checkpoints and toll-like receptors was different. Evidently, MSCs with unchanged cellular properties are present in human liver even at late stages of inflammatory diseases. These cells can be isolated and used as starting material in the development of cell therapies of liver diseases.

To evaluate the impact of cardiac arrest time (CAT) in brain-dead donors on graft and recipient outcomes following liver transplantation.

The outcome of livers from brain-dead donors with a history of cardiac arrest (CA) remains controversial, and the duration of the CAT has never been evaluated.

A retrospective review of data from the Scientific Registry of Transplant Recipients between 2003 and 2022 was conducted. Propensity score matching was performed to minimize confounding effects.

A total of 115,202 recipients were included, 7364 (6.4%) and 107,838 (93.6%) of whom were of the CA and non-CA group, respectively. After 1:1 propensity score matching, each group consisted of 7157 cases. The CA group demonstrated shorter hospital stay (15.5 ± 20.0 days vs. 16.2 ± 21.3 days, P = 0.041), with comparable incidence of early graft failure (EGF, 5.8% vs. 6.2%, P = 0.161). The CA group demonstrated slightly higher graft survival rates (1 year, 90% vs. 88%; 5 years, 76% vs. 74%; and 10 years, 61% vs. 58%, P < 0.001). CAT positively correlated with EGF [odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.02-1.04, P < 0.001], with a sensitivity and specificity of 73% and 86% at a cutoff of 30 minutes. The CAT <30 minutes group demonstrated significantly lower incidence of EGF (5.0%), compared with 7.8% of the CAT >30 minutes group and 6.2% of the non-CA group (P < 0.001).

The use of brain-dead donors with a history of CA did not increase the risk of liver graft failure in our study. A downtime of <30 minutes may confer protective effects on transplanted grafts.

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

Liver ischemia-reperfusion (I/R) injury is a common cause of organ failure, developed by a sudden block in the blood and oxygen supply and subsequent restoration. I/R damage is responsible for acute and chronic rejection after organ transplantation, accounting for 10% of early graft failure. The study investigated the therapeutic properties of fangchinoline in liver injury-induced rats. The rats were divided into three groups: Sham, I/R without pretreatment, and I/R + 10 mg/kg fangchinoline pretreatment. Blood and liver samples were collected for assays, and an in silico docking analysis was conducted to determine fangchinoline's inhibitory effect. The pretreatment with 10 mg/kg of fangchinoline effectively reduced hepatic marker enzymes such as AST, LDH, and ALT in the serum of rats with liver I/R damage. Fangchinoline treatment significantly reduced interleukin-8 (IL-8), IL-6, and tumor necrosis factor-α (TNF-α) in I/R-induced rats, boosting antioxidants and decreasing MDA. Histopathological studies showed liver injury protection, and fangchinoline inhibited TNF-α and IL-6 with improved binding affinity. Fangchinoline has hepatoprotective properties by reducing inflammation in rats with liver I/R damage, as demonstrated in the current study. Hence, it can be an effective salutary agent in preventing liver damage caused by I/R.

Thousands of people die or are removed from the liver transplant waitlist because of deterioration. One major challenge is the donor shortage. Increasing extended criteria donor (ECD) allograft usage can address this. We assessed whether transplanting ECD allografts provides a survival benefit versus remaining on the waitlist for standard allocation.

A retrospective analysis of 132 073 liver transplant recipients from 2002 to 2020 via the United National Organ Sharing database was performed. Three survival analyses were performed on model end-stage liver disease (MELD) score inclusive ranges: 8-9, 10-15, and 16-18. Within each analysis, cohorts were divided into "transplanted" or the corresponding "intent-to-treat (ITT)" category. The transplanted cohort was separated into 2 definitions of ECD allografts: donations after circulatory death and donations from donors older than 70 y, along with all-other allografts. Ten-year survival was compared between the 3 transplanted groups and the ITT group.

When adjusted for covariates, multivariable Cox proportional hazards regression analyses demonstrated that both ECD allografts and all-other allografts had better survival as compared with the ITT cohorts in each of separate analyses for MELD range 10-15 and MELD range 16-18 (P < 0.05).

In patients with MELD scores as low as 10, there is a survival benefit to using ECD allografts compared with those followed on an ITT basis.

The objectives of our study were to examine and compare patient and graft survival over a 5-year period across BMI groups, and examine immediate and short-term complications post-LT. This was a retrospective study that examined all liver transplants that occurred at our institution between January 2015-October 2022. Patients were divided into 4 BMI groups (n = 888): normal-overweight (BMI 18.5- 29.9 kg/m2), class I obesity (BMI 30-34.9 kg/m2), class II obesity (BMI 35-39.9 kg/m2), and class III obesity (BMI ≥40 kg/m2) patients. Kaplan Meier curves with the log rank test were created to assess survival outcomes and multivariate Cox regression analysis was performed. Patient and graft survival did not differ statistically between each BMI group. However, patient survival was significantly lower in patients with BMI ≥40 compared to patients with BMI <40. In multivariate analysis, BMI ≥40, admission to the ICU, and age were independent predictors of increased risk of mortality. Infection, arrhythmia, cardiac arrest, and myocardial infarction were more frequent immediate complications in the class III obesity group. Efforts to closely monitor patients with BMI ≥40 post LT to maximize survival are needed. Further studies are needed to improve post LT survival among patients with BMI ≥40.

Even with advancement of medical technologies, liver transplantation still faces several major challenges. Hence, other treatment modalities are urgently needed for patients with end-stage liver disease. Stem cells from human exfoliated deciduous teeth (SHED) was discovered to have highly proliferative and pluripotent properties; including differentiation into hepatocyte-like cells. This study aims to investigate the capability of intrasplenic transplanted SHED and SHED-Hep cells in inducing proliferation of stem cells and native hepatocytes in order to accelerate liver regeneration in liver fibrosis mice models.

Three carbon tetrachloride (CCl4)-injured male mice groups were used in this study. Two of those groups were transplanted with either SHED or SHED-Hep, while the other did not undergo transplantation. One age- and sex- matched healthy mice group was used as control. All specimens were immunohistochemically stained with anti-Ki-67 antibodies and anti-proliferating cell nuclear antigen (PCNA) antibodies before counter stained with hematoxylin-eosin.

Anti-Ki-67 antibodies staining: at both 8 and 12 weeks, proliferating activity was predominantly seen on both SHED- and SHED-Hep-transplanted CCl4-injured mice groups, while control and non-transplanted CCl4-injured mice group showed little to no sign of proliferation activity. Anti-PCNA staining: at both 8 and 12 weeks, significant proliferating activity was detected by PCNA staining, mainly on stem cells population area on SHED- and SHED-Hep-treated group.

In conclusion, this study has provided the evidence that transplantation of SHED or SHED-Hep on liver-injured mice induced proliferation of both transplanted stem cells and native liver cells in order to accelerate liver regeneration.

Generative artificial intelligence (AI), a subset of machine learning that creates new content based on training data, has witnessed tremendous advances in recent years. Practical applications have been identified in health care in general, and there is significant opportunity in transplant medicine for generative AI to simplify tasks in research, medical education, and clinical practice. In addition, patients stand to benefit from patient education that is more readily provided by generative AI applications. This review aims to catalyze the development and adoption of generative AI in transplantation by introducing basic AI and generative AI concepts to the transplant clinician and summarizing its current and potential applications within the field. We provide an overview of applications to the clinician, researcher, educator, and patient. We also highlight the challenges involved in bringing these applications to the bedside and need for ongoing refinement of generative AI applications to sustainably augment the transplantation field.

Developing new strategies for local monitoring and delivery of immunosuppression is critical to making allografts safer and more accessible. Ex vivo genetic modification of grafts using machine perfusion presents a promising approach to improve graft function and modulate immune responses while minimizing risks of off-target effects and systemic immunogenicity in vivo. This proof-of-concept study demonstrates the feasibility of using normothermic machine perfusion (NMP) to mimic in vitro conditions for effective gene delivery. In this study, lentiviral vectors carrying biosensor constructs with Gaussia Luciferase (GLuc) were introduced to rodent livers during a 72-hour perfusion period, with a targeted delivery of 3 × 107 infection units (IU). Following the initial 24-hour exposure required for viral transduction, an additional 48 hours was necessary to observe gene expression, analogous to in vitro benchmarks. The perfused livers displayed significantly increased luminescence compared to controls, illustrating successful genetic modification. These findings validate the ex vivo use of lentiviral particles in a rodent liver model and lay the groundwork for a broad range of applications through genetic manipulation of organ systems. Future studies will focus on refining this technology to enhance precision in gene expression and explore its implications for clinical transplantation.

Progressive familial intrahepatic cholestasis (PFIC) is a group of disorders characterized by inappropriate bile formation, causing hepatic accumulation of bile acids and, subsequently, liver injury. Until recently, no approved treatments were available for these patients.

Recent clinical trials for PFIC treatment have focused on intestine-restricted ileal bile acid transporter (IBAT) inhibitors. These compounds aim to reduce the pool size of bile acids by interrupting their enterohepatic circulation. Other emerging treatments in the pipeline include systemic IBAT inhibitors, synthetic bile acid derivatives, compounds targeting bile acid synthesis via the FXR/FGF axis, and chaperones/potentiators that aim to enhance the residual activity of the mutated transporters.

Substantial progress has been made in drug development for PFIC patients during the last couple of years. Although data concerning long-term efficacy are as yet only scarcely available, new therapies have demonstrated robust efficacy in a considerable fraction of patients at least on the shorter term. However, a substantial fraction of PFIC patients do not respond to these novel therapies and thus still requires surgical treatment, including liver transplantation before adulthood. Hence, there is still an unmet medical need for long-term effective medical, preferably non-surgical, treatment for all PFIC patients.

The aim of this study was to observe the recovery of liver function in patients with early allograft dysfunction (EAD) at one month postoperatively and explore whether early postoperative ultrasonic hemodynamic parameters can predict this outcome.

Patients with EAD postoperatively, who underwent orthotopic liver transplantation (OLT) in our hospital from December 2012 to June 2021, were retrospectively collected. Based on the recovery of liver function within one month, patients were divided into two groups: the recovery group (FR-1M) and the non-recovery group (Non-FR-1M). Ultrasonic hemodynamic parameters within the first seven days postoperatively were compared between the two groups.

Among the 254 EAD patients included in this study, 158 (62%) patients recovered their liver function within one month. Of the 96 (38%) patients who did not recover, The RI of the non-FR-1M group was significantly lower than that of the FR-1M group on postoperative day 6 (POD6) and POD7. In the high resistance interval (RI all > 0.7), Group FR-1M represents a significant proportion (29/3, ratio 12/1), while in the low resistance interval (RI < 0.5 at least once), Group non-FR-1M accounts for a relatively high proportion (12/27, ratio 5/11). In the middle resistance interval (more than 1 time ≤ 0.7 and all ≥ 0.5), the proportions of the two groups are balanced (85/88, ratio 1/1).

Liver function typically recovers within 1 month in most patients with EAD. The high resistance state of the hepatic artery in the early postoperative period is illustrative an important role in its recovery. Low-resistance state is most unfavorable for the recovery of liver function.

This is a cross-sectional observational study conducted on living liver donors focusing on "long-term remnant liver health" specifically looking at steatosis, inflammation, and fibrosis using multiparametric ultra sonological evaluation and noninvasive blood tests.

Multiparametric ultrasound evaluation included assessment of shear wave elastography (fibrosis), sound speed plane wave ultrasound, attenuation plane wave ultrasound (steatosis), and viscosity plane wave ultrasound (inflammation). Blood test based APRI and FIB-4 were calculated. Liver biopsy was performed if noninvasive evaluation pointed toward clinically relevant fibro progression (F4).

Out of 36 donors, significant fibrosis (>F2) was found in 11 donors (30.5%), seven donors (19.4%) had severe fibrosis (>F3), and two donors had shear wave elastography values suggestive of cirrhosis(F4). Of these two, one donor was extensively evaluated and was found to have biopsy proven cirrhosis with endoscopic evidence of portal hypertension. The prevalence of fatty liver disease in our study group was 50%.

We report the first liver donor cohort with fibroprogression and cirrhosis occurring in the remnant liver. Our donor cohort with a significant proportion having steatosis and fibroprogression underscores the importance of regular follow-up of liver donors and evaluation of remnant liver.

Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods.

To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs.

Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin.

This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states.

To generate pre-hospital symptom networks, explore core, bridge and sentinel symptoms, identify pre-hospital symptom clusters and analyse relationship between influencing factors and symptom clusters in decompensated cirrhosis patients.

A cross-sectional study design using the Strengthening the Reporting of Observational Studies in Epidemiology checklist.

Demographical, physiological, psychological and sociological characteristics and the pre-hospital symptoms of 292 decompensated cirrhotic patients were collected from October 2021 to March 2023 in China. Frequencies, percentages, means, standard deviations, independent samples t-tests, one-way analysis of variance, exploratory factor analysis, multiple stepwise regression analysis and network analysis were used for data analysis.

'I don't look like myself' and itching were core and bridge symptoms, while bloating and lack of energy were sentinel symptoms in decompensated cirrhotic patients. Monthly family income, anxiety, depression, social support and disease duration influenced the neuropsychological symptom cluster, with worrying as the strongest predictor symptom. Influential factors for cirrhosis-specific symptom cluster included Child-Pugh class, monthly family income, disease duration, anxiety and depression, with itching being the strongest predictor symptom. Monthly family income, disease duration and depression were influential factors for gastrointestinal symptom cluster, with loss of appetite as the strongest predictor symptom.

Neuropsychological, cirrhosis-specific and gastrointestinal symptom clusters were formed in decompensated cirrhotic patients. Through network analysis, direct connections between symptoms, symptom clusters and their influencing factors were revealed, thereby offering clinicians a foundation for effectively managing patients' pre-hospital symptoms.

Decompensated cirrhosis patients commonly have multiple symptoms, while the management of pre-hospital symptoms is often suboptimal. This study identified neuropsychological, cirrhosis-specific, gastrointestinal symptom clusters and recognized core, bridge and sentinel symptoms in these patients. It also revealed the most prominent symptoms within each cluster. This provides insight into the hierarchy of symptoms, improving symptom management in decompensated cirrhosis.

There was no patient or public involvement.

Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH.

Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC.

Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram.

This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR.

This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.

Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo study, we assessed HUDC safety and biodistribution in the NOD SCID mouse model at 90 days following the systemic intraosseous administration of HUDCs. Twelve NOD SCID mice (n = 6/group) received intraosseous injection of donor UCB cells (3.0 × 106) in Group 1, or HUDCs (3.0 × 106) in Group 2, without immunosuppression. Flow cytometry assessed hematopoietic cell surface markers in peripheral blood and the presence of HLA-ABC class I antigens in lymphoid and non-lymphoid organs. HUDC safety was assessed by weekly evaluations, magnetic resonance imaging (MRI), and at autopsy for tumorigenicity. At 90 days after intraosseous cell administration, the comparable expression of HLA-ABC class I antigens in selected organs was found in UCB control and HUDC therapy groups. MRI and autopsy confirmed safety by no signs of tumor growth. This study confirmed HUDC biodistribution to selected lymphoid organs following intraosseous administration, without immunosuppression. These data introduce HUDCs as a novel promising approach for immunomodulation in transplantation.

Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT.

Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed.

Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2.

In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models.

To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws.

Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI.

This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.

Hepatic artery thrombosis (HAT) is a devastating vascular complication following liver transplantation, requiring prompt diagnosis and rapid revascularization treatment to prevent graft loss. At present, imaging modalities such as ultrasound, computed tomography, and magnetic resonance play crucial roles in diagnosing HAT. Although imaging techniques have improved sensitivity and specificity for HAT diagnosis, they have limitations that hinder the timely diagnosis of this complication. In this sense, the emergence of artificial intelligence (AI) presents a transformative opportunity to address these diagnostic limitations. The develo pment of machine learning algorithms and deep neural networks has demon strated the potential to enhance the precision diagnosis of liver transplant com plications, enabling quicker and more accurate detection of HAT. This article examines the current landscape of imaging diagnostic techniques for HAT and explores the emerging role of AI in addressing future challenges in the diagnosis of HAT after liver transplant.

Regenerative medicine is taking a step forward in treating multiple diseases. The possibility of renewing damaged tissues with stem cells has become a topic of interest in recent decades. Still a relatively new research topic, many issues in this discipline are being addressed, from cell culturing to the study of different graft materials, and, moreover, cell delivery. For instance, direct intravenous injection has a big downfall regarding its lack of precision and poorly targeted treatment. Trans-arterial and direct percutaneous infusion to the aimed tissue/organ are both considered ideal for reaching the desired region but require image guidance to be performed safely and precisely. In this context, interventional radiology becomes pivotal for providing different cell delivery possibilities in every case. In this review, we analyze different basic stem cell therapy concepts and the current and future role of interventional radiology with a focus on trans-arterial delivery.

ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration.

The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire.

Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants.

With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study.

Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival.

62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI ​= ​2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios.

Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.

Identification of chronic rejection risk factors in liver transplant recipients is critical for early detection and prevention of further graft loss. We investigated characteristics of liver transplant recipients who had experienced chronic rejection and the associated risk factors versus patients without chronic rejection.

Data from 3022 adult liver transplant recipients between 2011 and 2018 were analyzed; of these, 80 patients had experienced chronic rejection. The control group included 98 randomly selected liver transplant recipients who did not have chronic rejection.

The age of the recipients and the donors was significantly lower in the group with chronic rejection versus the group without chronic rejection.The results indicated that chronic rejection was significantly associated with the sex of the recipients (hazard ratio 3.2, 95% CI 1.77-6.08; P < .001) and with the sex concordance between the recipients and donors (hazard ratio 2.93, 95% CI 1.67-5.13; P < .001, respectively). Also, in the group without chronic rejection, there were no male donors; however, the group with chronic rejection had mostly male donors (P <.001). Cold ischemia time was longer in patients with chronic rejection versus that shown in the control group (P = .031), and there was a significant difference between the 2 groups in acute rejection frequency (P < .001).

Recipient sex and sex concordance were independent risk factors for chronic rejection. Most transplantrecipients with chronic rejection responded to medicaltreatment, and the rate of graftloss was low among our recipients.

The high prevalence of liver cirrhosis in Slovakia leads to a great need for transplant treatment. The outcome of liver transplantation is influenced by several factors.

The main objective of this study is to test the effectiveness of prehabilitation compared to standard of care.

Prospective, double-arm, randomized, open-registry study.

Patient in F. D. Roosevelt Teaching Hospital, Slovakia, Banská Bystrica.

The participants consisted of patients with liver cirrhosis (55 men, 25 women).

The patients were randomized to the active prehabilitation group (N.=39) or the standard of care group (SOC) (N.=41). SOC represents the standard of care for patients prior to liver transplantation, consisting of a formal oral interview lasting 30 minutes. In addition to SOC, each patient with decompensated liver cirrhosis also underwent a prehabilitation intervention that included rehabilitation and nutrition support. Patients completed the exercises under the supervision of a physician during hospitalisation.

After one month, the liver frailty index improved in the prehabilitation group (P=0.05). No improvement in MELD (Model of End Stage Liver Disease) was found in the group that underwent the prehabilitation program (P=0.28), and no improvement was found in the Child-Pugh score after one month (P=0.13). In the prehabilitation groups compared with the SOC group, differences were not found in the MELD score (P=0.11). Better clinical outcomes according to the Child-Pugh score was found for the prehabilitation group compared with the SOC group (P=0.02). According to LFI, there was no difference between the groups (P=0.26). Very low adherence was found after three months. Only three patients in the SOC group and six patients in the prehabilitation group came to the check-up. Due to low adherence after 3 months in patients with liver cirrhosis, it is not possible to make an adequate comparison between groups after three months.

Despite the great effort to maintain adherence, it was not possible to draw a conclusion about the effectiveness of prehabilitation in patients before liver transplantation compared to standard of care because the main problem in Slovak patients with liver cirrhosis is low adherence. More studies are needed to identify the barriers that lead to low adherence in patients with liver cirrhosis.

A promising result was found due to improvement of the Liver Frailty Index and the Child-Pugh Score after one month in the prehabilitation group.

As the only reliable treatment option for end-stage liver diseases, conventional liver transplantation confronts major supply limitations. Accordingly, the decellularization of discarded livers to produce bioscaffolds that support recellularization with progenitor/stem cells has emerged as a promising translational medicine approach. The success of this approach will substantially be determined by the extent of extracellular matrix (ECM) preservation during the decellularization process. Here, we assumed that the matrix metalloproteinase (MMP) inhibition could reduce the ECM damage during the whole liver decellularization of an animal model using a perfusion-based system. We demonstrated that the application of doxycycline as an MMP inhibitor led to significantly higher preservation of collagen, glycosaminoglycans, and hepatic growth factor (HGF) contents, as well as mechanical and structural features, including tensile strength, fiber integrity, and porosity. Notably, produced bioscaffolds were biocompatible and efficiently supported cell viability and proliferation in vitro. We also indicated that produced bioscaffolds efficiently supported HepG2 cell function upon seeding onto liver ECM discs using albumin and urea assay. Additionally, MMP inhibitor pretreated decellularized livers were more durable in contact with collagenase digestion compared to control bioscaffolds in vitro. Using zymography, we confirmed the underlying mechanism that results in these promising effects is through the inhibition of MMP2 and MMP9. Overall, we demonstrated a novel method based on MMP inhibition to ameliorate the ECM structure and composition preservation during liver decellularization as a critical step in fabricating transplantable bioengineered livers.

Although transfusion management has improved during the last decade, orthotopic liver transplantation (OLT) has been associated with considerable blood transfusion requirements which poses some challenges in securing blood bank inventories. Defining the predictors of massive blood transfusion before surgery will allow the blood bank to better manage patients' needs without delays. We evaluated the predictors of intraoperative massive transfusion in OLT.

Data were collected on patients who underwent OLT between 2007 and 2017. Repeat OLTs were excluded. Analyzed variables included recipients' demographic and pretransplant laboratory variables, donors' data, and intraoperative variables. Massive transfusion was defined as intraoperative transfusion of ≥10 units of packed red blood cells (RBCs). Statistical analysis was performed using SPSS version 17.0.

The study included 970 OLT patients. The median age of patients was 57 (range: 16-74) years; 609 (62.7%) were male. RBCs, thawed plasma, and platelets were transfused intraoperatively to 782 (80.6%) patients, 831 (85.7%) patients, and 422 (43.5%) patients, respectively. Massive transfusion was documented in 119 (12.3%) patients. In multivariate analysis, previous right abdominal surgery, the recipient's hemoglobin, Model for End Stage Liver Disease (MELD) score, cold ischemia time, warm ischemia time, and operation time were predictive of massive transfusion. There was a direct significant correlation between the number of RBC units transfused and plasma (Pearson correlation coefficient r = .794) and platelets (r = .65).

Previous abdominal surgery, the recipient's hemoglobin, MELD score, cold ischemia time, warm ischemia time, and operation time were predictive of intraoperative massive transfusion in OLT.

In 2021, the National Academy of Medicine began collaborating with YouTube to highlight high-quality channels for patients seeking medical information. This study evaluates whether YouTube videos from accredited publishers are useful for patients searching for information regarding liver transplantation.

After searching "Liver Transplant" on YouTube, the first 100 results under 10 min long with English text or audio were transcribed. The Flesch-Kincaid grade level was used to quantify reading grade level. Viewership metrics and the accreditation status of the video publisher were identified. The DISCERN score was used to grade the quality of medical information. We adapted an informed consent curriculum for surgical interns to create an eight-point content metric that we coined the "Anderson-Lau score". Higher scores indicated higher content quality. Statistical significance was calculated using Wilcoxon rank-sum and chi-squared tests with a significance level of P = 0.05.

Of the 100 videos assessed, 37 met the average American reading level (8th grade) and none met the reading level of the average Medicare patient (5th grade). The median Flesch-Kincaid grade level was 9th grade. The median content ("Anderson-Lau") and quality (DISCERN) scores were 2/8 and 1/5, respectively. While 56% of videos mentioned operative indications and benefits, under 25% mentioned operative steps, risks, alternatives, and postoperative expectations. A total of 75 videos were from accredited publishers, and there was no significant difference between the quality of videos from accredited and unaccredited publishers.

Videos made by accredited sources regarding liver transplantation were not of higher educational quality or content. More informative educational materials are needed to advise patients about liver transplantation, help them understand the procedure, and to supplement discussions with their transplant team.

Living Donor Liver Transplantation (LDLT) is a promising approach to treating end-stage liver diseases, however, some post-operatory complications such as pneumonia, bacteremia, urinary tract infections, and hepatic dysfunction have been reported. In murine models using partial hepatectomy (PHx), a model that emulates LDLT, it has been determined that the synthesis of hepatic cell proliferation factors that are associated with noradrenaline synthesis are produced in locus coeruleus (LC). In addition, studies have shown that PHx decreases GABA and 5-HT2A receptors, promotes loss of dendritic spines, and favors microgliosis in rat hippocampus. The GABA and serotonin-altered circuits suggest that catecholaminergic neurons such as dopamine and noradrenaline neurons, which are highly susceptible to cellular stress, can also be damaged. To understand post-transplant affections and to perform well-controlled studies it is necessary to know the potential causes that explain as a liver surgical procedure can produce brain damage. In this paper, we review several cellular processes that could induce gliosis in LC after rat PHx.

Acute and chronic liver diseases cause significant morbidity and mortality worldwide, affecting millions of people. Liver transplantation is the primary intervention method, replacing a non-functional liver with a functional one. However, the field of liver transplantation faces challenges such as donor shortage, postoperative complications, immune rejection, and ethical problems. Consequently, there is an urgent need for alternative therapies that can complement traditional transplantation or serve as an alternative method. In this review, we explore the potential of liver tissue engineering as a supplementary approach to liver transplantation, offering benefits to patients with severe liver dysfunctions.

Emerging computational tools such as healthcare digital twin modeling are enabling the creation of patient-specific surgical planning, including microwave ablation to treat primary and secondary liver cancers. Healthcare digital twins (DTs) are anatomically one-to-one biophysical models constructed from structural, functional, and biomarker-based imaging data to simulate patient-specific therapies and guide clinical decision-making. In microwave ablation (MWA), tissue-specific factors including tissue perfusion, hepatic steatosis, and fibrosis affect therapeutic extent, but current thermal dosing guidelines do not account for these parameters. This study establishes an MR imaging framework to construct three-dimensional biophysical digital twins to predict ablation delivery in livers with 5 levels of fat content in the presence of a tumor. Four microwave antenna placement strategies were considered, and simulated microwave ablations were then performed using 915 MHz and 2450 MHz antennae in Tumor Naïve DTs (control), and Tumor Informed DTs at five grades of steatosis. Across the range of fatty liver steatosis grades, fat content was found to significantly increase ablation volumes by approximately 29-l42% in the Tumor Naïve and 55-60% in the Tumor Informed DTs in 915 MHz and 2450 MHz antenna simulations. The presence of tumor did not significantly affect ablation volumes within the same steatosis grade in 915 MHz simulations, but did significantly increase ablation volumes within mild-, moderate-, and high-fat steatosis grades in 2450 MHz simulations. An analysis of signed distance to agreement for placement strategies suggests that accounting for patient-specific tumor tissue properties significantly impacts ablation forecasting for the preoperative evaluation of ablation zone coverage.

Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.

Liver transplantation is the ultimate treatment option for end-stage liver failure. However, liver graft injury remains a challenge. This study aimed to investigate the role of connexin32 (Cx32) in liver graft injury and elucidate its mechanism of action. Through detecting liver graft samples from 6 patients, we observed that changes in the Cx32 level coincided with liver graft injury. Therefore, we established autologous orthotopic liver transplantation (AOLT) models using Cx32-knockout and wild-type mice and hypoxia/reoxygenation (H/R) and lipopolysaccharide (LPS) pretreatment models using alpha mouse liver 12 (AML12) cells, to explore Cx32 mechanisms in liver graft injury. Following in vivo and in vitro Cx32 knockout, oxidative stress and inflammatory response were inhibited through the regulation of PKC-α/NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, thereby reducing Bak/Bax-related apoptosis and ameliorating liver graft injury. When the Cx32-based gap junction (GJ) was blocked with 2-aminoethoxydiphenyl borate (2-APB), ROS transfer was attenuated between neighboring cells, exacerbated oxidative stress and inflammatory response were prevented, and aggravation of liver graft injury was mitigated. These results highlight the dual regulation mechanism of Cx32 in liver graft injury. Through interaction with PKC-α, Cx32 regulated the NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, thus directly triggering oxidative stress and inflammatory response. Simultaneously, mass-produced ROS were transferred to neighboring cells through Cx32 channels, for which oxidative stress and the inflammatory response were aggravated indirectly. Finally, Bak/Bax-related apoptosis was activated, thereby worsening liver graft injury. Our findings propose Cx32 as a dual mechanistic factor for oxidative stress and inflammatory signaling pathways in regulating cell apoptosis on liver graft injury, which suggests a promising therapeutic targets for liver graft injury.

Perihilar cholangiocarcinoma (pCCA) is a highly malignant tumor arising from the biliary tree. Radical surgery is the only treatment offering a chance of long-term survival. However, limited by the tumor's anatomic location and peri-vascular invasion, most patients lose the chance for curative treatment. Therefore, more methods to increase the resectability of tumors as well as to improve outcomes are needed.

A 68-year-old female patient had a hepatic hilar mass without obvious symptoms. Laboratory results showed hepatitis B positivity. Magnetic resonance imaging indicated that the mass (maximum diameter: 41 mm) invaded the left and right branches of the main portal vein, as well as the middle, left and right hepatic veins; enlarged lymph nodes were also detected in the hilum. The patient was diagnosed with pCCA, and the clinical stage was determined to be T4N1M0 (stage IIIC). Considering the tumor's anatomic location and vascular invasion, systematic conversion therapy followed by ex vivo liver resection and autotransplantation (ELRA) was determined as personalized treatment for this patient. Our original systemic sequential therapeutic strategy (lenvatinib and tislelizumab in combination with gemcitabine and cisplatin) was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment, without severe toxicity. ELRA, anastomotic reconstruction of the middle hepatic vein, right hepatic vein, root of portal vein, inferior vena cava and right hepatic artery, and lymph node dissection were performed at one month after systemic therapy. Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis. Although the middle hepatic vein was partially obstructed four months later, hepatic vein stent implantation successfully addressed this problem. The patient has survived for 22 mo after the diagnosis, with no evidence of recurrence or metastasis.

An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.