Several advances in liver transplantation (LT) have provided an increased rate in 1-year patient survival, currently reported between 84.5% and 91.4%. However, this significant improvement is not widely maintained after the 1-year of follow-up. In this study, we analyze short-term and long-term results in LT recipients.

A retrospective observational cohort study, including patients who underwent LT between 1990 and 2009 and were followed for a minimum 15-year period, analyzing the causes and risk factors of mortality and patient and graft survival from LT up to the last outpatient visit.

A total of 594 patients with LT were included (median age, 53-year and 69.7% male). The most common indications for LT were HCV-cirrhosis (267 patients), alcoholic cirrhosis (250 patients), and hepatocellular carcinoma (HCC) (144 patients). Post-LT complications were acute rejection in 44.1%, cardiovascular in 40.6%, chronic kidney disease in 40.1%, hypertension in 22.6%, and de novo tumors in 25.6%. Retransplantation was performed in 40 (6.7%) patients. A total of 388 (65.3%) patients died during a follow-up over 20 years: 106 (17.8%) in the first year post-LT; 76 (12.8%) between 2 and 5 years; 75 (12.6%) between 6 and 10 years; 73 (812.3%) between 11 and 15 years; 30 (5%) between 16 and 20 years; and 28 (4.7%) after 20 years. The overall causes of death were infection in 69 (11.6%) patients, cardiovascular complications in 58 (9.8%) patients, pulmonary complications in 8 (1.3%) patients, liver graft failure in 126 (21.2%) patients, HCC recurrence in 15 (2.6%) patients, de novo tumors in 72 (12.1%) patients, and miscellaneous in 40 (6.7%) patients. Rates of actuarial patient survival at 1-, 3-, 5-, 10-, 15-, and 20-year after LT were 82.7%, 75.6%, 70%, 58.6%, 45.2%, and 37.6%, respectively, and actuarial graft survival were 80%, 72.5%, 67.1%, 54.8%, 42.6%, and 34.6%, respectively. Advanced recipient age, blood transfusion, and infection were the main risk factors for patient mortality.

The highest mortality rate was within the first year of LT, and the most common causes of death were hepatic failure, de novo tumors, infection, cardiovascular disease, and HCC recurrence.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the primary hepatic malignancies with established pathways to transplantation and model for end-stage liver disease (MELD) exception points. Other tumors managed with liver transplantation (LT) include hepatic epithelioid hemangioendothelioma and fibrolamellar HCC. LT for metastatic neuroendocrine tumor has been established with patient selection criteria and a path to MELD exception points. Additionally, recent data on LT for patients with unresectable hepatic colorectal metastases demonstrate increasingly encouraging initial results.

Systemic inflammation drives the progression of portal hypertension in patients with liver cirrhosis. Interleukin-6 is a key mediator of the cytokine network in acute inflammation that stimulates the production of many acute phase reactants. In this study, we investigated the association between serum interleukin-6 and acute phase reactant levels and the disease stage and prognosis of patients with liver cirrhosis.

A single-center retrospective cohort of 359 patients with liver cirrhosis was staged according to the symptomatic decompensation. Baseline serum C-reactive protein , interleukin-6, procalcitonin, and serum amyloid A protein levels were measured. The outcomes of further decompensation, hepatocellular carcinoma development, and mortality were identified during a 3.3-year median follow-up period.

Serum C-reactive protein , interleukin-6, and procalcitonin levels were significantly different across the stages. The multivariate Cox proportional hazards model identified serum interleukin-6 as an independent predictor of further decompensation in patients with compensated and the first single decompensated cirrhosis. Kaplan-Meier analyses showed that the probability of further decompensation was stratified by serum interleukin-6 level in a dose-dependent manner. In the entire cohort, serum interleukin-6 level also showed a significant association with liver-related and all-cause mortalities, but not with hepatocellular carcinoma development, independent of stage and liver disease severity indices.

Elevated levels of serum markers of systemic inflammation were associated with symptomatic decompensation, and serum interleukin-6 level is a predictor of further decompensation and mortality in patients with liver cirrhosis.

Liver transplantation (LT) is the gold standard for end-stage liver disease, but ischemic cholangiopathy (IC) remains a significant complication. Ex-situ normothermic machine perfusion (ESNMP) has emerged as a potential strategy to mitigate ischemic injury. However, the effect of ESNMP on reducing post-LT IC remains controversial. This study aimed to perform an updated meta-analysis to evaluate the impact of ESNMP on IC incidence.

A systematic review and meta-analysis were conducted following PRISMA guidelines. The literature search included studies from 2015 to 2025 comparing LT outcomes using ESNMP vs. static cold storage (SCS). The primary outcome was the incidence of IC. Risk of bias was assessed using the ROBINS-E tool. Statistical analysis, including random-effects meta-analysis, sensitivity analysis, and meta-regression, was performed to evaluate heterogeneity, potential confounders, and the impact of follow-up duration.

Seventeen studies, including 76,045 patients (4843 ESNMP; 71,202 SCS), were analyzed. No statistically significant difference in IC incidence was found between ESNMP and SCS (1.3 % vs. 0.6 %; RR = 0.68, 95 %CI = 0.41-1.13; P = 0.14). Sensitivity analysis excluding one outlier study revealed a reduction in IC risk with ESNMP (RR = 0.62, 95 %CI = 0.38-1.01; P = 0.054). Two sub-analyses of studies with ≥12 months of follow-up (RR = 0.51, 95 %CI = 0.26-0.99; P = 0.049) and DCDs (RR = 0.33, 95 %CI = 0.16-0.67; P = 0.002) showed risk reduction. The meta-regression revealed that the back-to-base perfusion approach was associated with the occurrence of IC, with an OR of 1.03 (95 %CI = 1.00-1.07, P = 0.035).

a correlation between ESNMP use and IC reduced risk appears to exist, especially with longer follow-up periods and DCDs, though more high-quality studies are needed to confirm this finding.

Pregnancy after orthotopic liver transplantation (OLT) puts the mother, child, and transplanted organ at risk. Little is known about long-term outcomes. We performed a nationwide retrospective cohort study to evaluate short-term and long-term outcomes of post-OLT pregnancies. The secondary aim was to assess predictors for adverse pregnancy outcomes. A composite outcome of preeclampsia, preterm birth, low birth weight, and neonatal intensive care unit admission was made. Survival of women who received a transplant at <50 years of age with and without pregnancy after OLT were compared (Dutch Organ Transplantation Registry data). Descriptive statistics, regression analysis, Kaplan-Meier and log-rank analysis, and generalized estimating equation analysis were used. Among the included 70 women with 113 pregnancies >20 weeks of gestation, hypertension occurred in 20% and preeclampsia in 12%. The live birth rate was 87%; 33% were preterm, and 23% had low birth weight. Long-term follow-up (median 10 y [IQR: = 4-14]) showed small changes in serum creatinine and bilirubin ( p < 0.001). Sixteen mothers (23%) died during follow-up (median 8 y [IQR: = 4-12]), with all their children aged <18 years. No difference in survival was found when comparing women with and without pregnancy after OLT. The composite outcome occurred in 43/98 of pregnancies. Higher body mass index (BMI) and maternal age at conception increased the composite outcome risk (OR: 1.24, p < 0.01, and OR: 1.25, p = 0.01, respectively). To conclude, pregnancy after OLT does not seem to influence long-term outcomes of graft, kidney function, or patient survival in most cases. However, although pregnancy does not seem to impact survival after OLT, we do show that a substantial number of children will lose their mothers early in life. We believe this is important for pregnancy couseling of patients with an OLT and their partners.

Hepatitis B virus (HBV) remains a leading etiology for liver transplantation (LT). In a large cohort of HBsAg-positive patients, this study evaluates long-term patient and graft survival after LT over the past 30 years while analyzing trends and outcomes following waiting list (WL) inclusion over the last 15 years.

HBsAg-positive patients who underwent transplantation between 1991 and 2020 and were waitlisted from 2006 to 2020 at Padua Hospital were included in the analysis. Patients were stratified according to hepatitis delta virus (HDV) coinfection, transplant indication (decompensated cirrhosis vs. hepatocellular carcinoma (HCC)), and WL inclusion period.

Among 321 HBsAg-positive LT recipients (31.5% HDV-coinfected, 46.4% HCC), 1-year and 5-year patient/graft survival rates were 87.6%/86.7% and 82.6%/82.2%, respectively. From 2006 to 2020, 284 HBsAg-positive patients were waitlisted (32.6% HDV-coinfected), with a significantly higher prevalence of HCC compared to non-HBV patients (p = 0.008). High-barrier nucleos(t)ide analogues (hbNUCs) significantly reduced mortality (p = 0.041) and improved survival post-WL inclusion (p = 0.007). Survival rates were consistent regardless of LT indication, HDV coinfection, or WL inclusion period. Post-transplant prophylaxis predominantly involved immunoglobulins (HBIG) + NUCs, resulting in only two cases of HBV reactivation, both clinically inconsequential.

Over the past 30 years, HBV has remained a consistent indication for LT at our center. Thanks to hbNUCs, WL outcomes have improved and HCC has become the main indication for LT.

Patients with hepatitis D virus (HDV)/hepatitis B virus (HBV)-related end-stage liver disease candidates for liver transplantation (LT) have traditionally been regarded as a special population, although their outcomes are controversial. An intention-to-treat (ITT) analysis of long-term outcomes of HDV/HBV-coinfected patients waitlisted for LT in Italy, between 2011 and 2020, was performed and compared with HBV-monoinfected LT candidates. Of 1731 HBV-infected LT candidates, 1237 (71.5%) had HBV monoinfection and 494 (28.5%) HDV/HBV coinfection. At listing, HDV/HBV-coinfected patients were significantly younger, listed mainly for decompensated cirrhosis, and with fewer hepatocellular carcinoma (HCC) cases; (26% vs 65.8%; P <.0001) compared with HBV-monoinfected patients. HDV/HBV-coinfected patients showed better 5-year ITT survival (83.2%; 95% CI: 79.4%-83.4%, vs 71.6%; 95% CI: 68.8%-74.2%; P < .0001). ITT-multivariable analysis identified the presence of HCC, advanced recipient age, and high model for end-stage liver disease-Na scores as mortality risk factors. Five years after LT, 99.1% of HDV/HBV-coinfected patients received oral nucleos(t)ide analogs, with immunoglobulins against antigen of the hepatitis B virus in 91.8% of cases. HBV and HDV viral recurrences were 1.1% and 0.2%, respectively, whereas recurrent or de novo HCC were 8.9% and 0.3%, respectively. In Italy, HDV/HBV-coinfected patients waitlisted for LT showed more favorable outcomes compared with HBV-monoinfected patients, both before and after LT. These excellent results, from the largest cohort reported so far, suggest that HDV/HBV-coinfected LT recipients do not represent a risky population and may be considered for simpler long-term antiviral prophylactic strategies.

Conflicting data exist regarding optimal prophylaxis for HBV recurrence (HBV-R) after liver transplantation (LT), particularly in patients with hepatocellular carcinoma (HCC). We assessed current practices for HBV-R prophylaxis in Italy, evaluating rates, risk factors, and the clinical impact of HBV-R and HCC-R.

We performed a multicentric, retrospective study involving 20 Italian LT centers. All patients who underwent LT for HBV-related liver diseases between 2010 and 2021 were included. Logistic regression was used to identify predictors of HBV-R and HCC-R. Survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test.

We included 1,205 LT recipients (60.8% with HCC). HBV prophylaxis was prescribed in 99.7% of recipients, mostly with lifelong hepatitis B immunoglobulin+nucleos(t)ide analogues (HBIG+NUCs) (83.9%). Rates of HBV-R were 2.1% and 3.1% in patients transplanted without and with HCC, respectively. Median times from LT were 60 [9.5-77.5] and 5.5 [1-13] months, respectively. Recipients on lifelong HBIG+NUCs experienced lower rates of HBV-R than those in whom HBIG was withdrawn, used only during LT, or in those who received NUCs alone (2.3% vs. 6.2% vs. 1.9% vs. 8%, respectively; p = 0.042). In recipients with HCC, HCC-R rate was 10.8% (median time from LT: 18 months). At multivariate analysis, HBV-R (odds ratio [OR] 10.329; 95% CI 3.665-29.110), Child-Pugh C (OR 3.519; 95% CI 1.305-9.484), and microvascular invasion (OR 3.088; 95% CI 1.692-5.634) were independently associated with HCC-R. Five-year survival was lower in recipients who experienced HCC-R (32.5% vs. 92.4% in those who did not; p <0.001).

In Italy, HBV prophylaxis is mostly based on lifelong HBIG+NUCs. HBV-R was rare and not associated with survival in patients transplanted for decompensated cirrhosis. In patients transplanted for HCC, HBV-R was independently associated with HCC-R. The clinical implications of these findings deserve further investigation.

In Italy, the combination of high-barrier nucleos(t)ide analogues and hepatitis B immunoglobulins remains the most widely used regimen for antiviral prophylaxis following liver transplantation for HBV-related liver disease. Hepatitis B recurrence after liver transplantation is a rare event and not associated with reduced survival. In transplant recipients with hepatocellular carcinoma, HBV recurrence was independently associated with hepatocellular carcinoma recurrence, though this may simply reflect an epiphenomenon without any causal relationship.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a significant global health challenge due to its high mortality rate. The epidemiology of HCC is closely linked to the prevalence of chronic liver diseases, the predominant etiology being hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD). HCC incidence varies widely globally, with the highest rates observed in East Asia and sub-Saharan Africa. This geographic disparity is largely attributed to the endemicity of HBV and HCV in these regions. In Western countries, the incidence of HCC has been rising, driven by increasing rates of alcohol abuse and the presence of steatosis liver disease. MASLD-associated HCC has a higher body mass index, a higher rate of type 2 diabetes mellitus, hyperlipidemia, hypertension, and association with cardiovascular diseases. Steatosis-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related liver disease and viral hepatitis. Prevention strategies vary by region, focusing on vaccination against HBV, antiviral treatments for HBV and HCV, alcohol moderation, and lifestyle interventions along with weight reduction to reduce obesity and incidence of MASLD-related HCC incidence.

The optimal calcineurin inhibitor after liver transplantation (LT) for primary biliary cholangitis (PBC) remains debated. We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis from the Scientific Registry of Transplant Recipients. We included adults with PBC who underwent primary LT from 1995 to 2022. Patients with initial cyclosporine treatment were 1:3 matched with those with initial tacrolimus treatment, ensuring exact calendar-period match. Primary outcomes were patient and graft survival. After matching, 579 patients with PBC and initial cyclosporine and 1348 with tacrolimus were well balanced for baseline characteristics. During a median follow-up of 11.1 years, 1044 (54%) deaths and 124 (6%) re-LTs occurred. In the overall matched sample, no significant survival difference emerged between cyclosporine and tacrolimus. However, tacrolimus conferred a survival advantage in some secondary analysis, such as LT after year 2000 and women, and in a 6-month landmark analysis excluding early postoperative events and calcineurin inhibitor switches. Cyclosporine did not reduce graft loss from PBC recurrence or affect laboratory markers of recurrence. In conclusion, we found no benefit of starting immunosuppression with cyclosporine after LT for PBC.

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.

Liver transplantation is the only curative option for patients with advanced stages of liver disease, with tacrolimus used as the immunosuppressive drug of choice. Genetic variability can interfere with drug response, potentially leading to overexposure or underexposure. This study aims to investigate the association of CYP3A4 (rs2740574, rs2242480, rs35599367), CYP3A5 (rs776746, rs10264272), POR (rs1057868) and ABCB1 (rs1128503, rs2229109, rs9282564) gene polymorphisms with infection, acute rejection, and renal failure. The logistic regression model found an influence of CYP3A5 (rs776746) and POR28 (rs1057868) on the development of acute rejection after liver transplantation (p = 0.028). It also found an association between carriers of the variant allele of the POR*28 gene and infection.

Invasive fungal infection (IFI) is a severe complication in organ transplant patients and a major diagnostic and therapeutic challenge. The aim of this comprehensive retrospective study was the characterization of IFI in context of chronic liver transplant failure regarding prevalence, morphological changes, and inducing fungal species. All explanted liver transplants due to chronic transplant failure from Heidelberg University Hospital were extensively reexamined for the presence of mycotic infection. Special stains were performed to uncover severity and associated conditions of IFI and fungal species were identified on the molecular level. Light-microscopic examination revealed fungal infection in 41 (27.5%) of 149 explanted livers with chronic transplant failure, with 68% representing newly specified cases compared to primary reports. We could show an increase of the proportion of mycotic infections during the investigated time period (1991-2021) as well as a shorter transplant survival when compared to the non-affected organs. Typically, large bile ducts were affected, accompanied by acute inflammation with frequent abscess and bile concrement formation. In 35 of 41 cases, the identification of the fungal species was achieved, revealing Candida albicans as prominent species (74.3%). In three autopsy livers of patients that died after liver transplantation of septic multiorgan failure, Candida spp. could be identified. Our data show the underestimated prevalence and high diagnostic and clinical relevance of mycotic infection in chronic liver transplant failure. Adapting diagnostic procedures, molecular pathological analyses, and therapeutic strategies is relevant to identify and prevent chronic transplant organ failure caused by IFIs.

In China, liver transplantation is an important discipline in the field of organ transplantation. China Liver Transplant Registry (CLTR) is a scientific project that has been set up to advance surgical techniques and procedures and to improve both short- and long-term post-transplant follow-up and outcome of the liver recipients. CLTR also serves as a robust data support platform for the National Liver Transplant Quality Control Center in the quest to upscale its quality control protocols. The mission of CLTR is to register all liver transplantation activities in the mainland of China and to conduct scientific analyses of the collected data. The huge number of compiled cases and the scientific research conducted over the past decade based on this database drastically revolutionized the clinical practice in the country. All CLTR activities and projects will be a guarantee to foster progresses of liver transplantation in China in a more scientific way, to standardize the systematic care in the field of liver transplantation.

Tumor recurrence, the Gordian knot of liver transplantation for malignancies, may be attributed to many parameters. The technique of the "classical" recipient hepatectomy is believed to be one of the potential reasons to cause tumor evasion because of the possible increase of circulating tumor cells, thus leading to an increased recurrent rate. On this background, the no-touch oncological recipient hepatectomy technique has been developed. A comprehensive review of the development and the key surgical steps of the no-touch recipient hepatectomy is presented. This technique might improve clinical outcomes, especially for those recipients who are at a high risk for tumor recurrence. Multicenter prospective studies should be set up to further validate the prognostic role of this technique in patients with liver cancer treated with liver transplantation.

Mitochondrial dysfunction mediated by c-Jun N-terminal kinase (JNK) plays an important role in lipotoxic liver injury in nonalcoholic steatohepatitis (NASH). This study aims to investigate the pharmacological mechanism of Jiangzhi Granule (JZG), a Chinese herbal formula against NASH, with a focus on its regulation of JNK signaling-mediated mitochondrial function.

Hepatocytes were induced by palmitic acid (PA) for 24 h to establish an in vitro lipotoxic model, which was simultaneously treated with either JZG or vehicle control. Male C57BL/6J mice were fed a high-fat diet (HFD) for 22 weeks and then treated with JZG via gavage for additional 8 weeks. Lipotoxic injury in hepatocytes or mice liver tissues, as well as JNK signaling-related molecules, were further investigated.

JZG improved PA-induced lipid deposition, cell viability, apoptosis, and mitochondrial dysfunction in hepatocytes. In NASH mice, JZG reduced hepatosteatosis, and inflammatory infiltration, and improved mitochondrial morphology and quantity in liver tissues. Additionally, elevated phosphorylation ratio of non-receptor tyrosine kinase c-Src (Src) and reduced phosphorylation ratio of JNK and SH2-containing protein tyrosine phosphatase (SHP-1) were found in both hepatocytes and mice liver tissues treated with JZG versus those with the vehicle.

Taken together, JZG could improve mitochondrial dysfunction and reduce lipotoxic liver injury in NASH in vivo and in vitro models. The inhibition of the JNK signaling pathway may contribute to the underlying mechanism of JZG in preventing and reversing NASH development.

Patients with cirrhosis-associated and portal hypertension-associated complications may benefit from TIPS and/or liver transplantation. In many patients, the decision of whether or not TIPS should be placed prior to liver transplantation is fairly clear-cut. Nevertheless, there are some patients in whom the decision can be more complex. On one hand, TIPS is easily available in contrast to liver transplantation, and patients with TIPS may have clinical improvement. On the other hand, although TIPS may improve the situation of the patient, this improvement may not be sufficient to significantly improve the quality of life. Furthermore, TIPS malposition may be challenging for liver transplantation surgery. This review approaches the advantages and disadvantages of TIPS placement in patients who are candidates for liver transplantation and proposes decision pathways for patients with complications of portal hypertension on the liver transplant waiting list.

With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options.

This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months.

Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009).

Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis.

NCT04895943.

Introduction We aimed to assess whether partial hepatectomy has an influence on conventional and speckle tracking parameters on echocardiography in living liver donors in the early postoperative period. Methods This study was a retrospective study to investigate the cardiac effects of liver donation after the transplant operation in a high-volume liver transplant center. Ninety living liver donors were included in the study. The echocardiographic images were obtained from 90 living liver donors before and five to seven days after the operation. The echocardiographic examinations were evaluated with a Philips Epiq 7 ultrasound system (Philips Ultrasound; Bothell, WA, USA) by experienced cardiologists in accordance with the recommendations of the American Society of Echocardiography. These included M-mode, two-dimensional imaging, tissue Doppler assessment at the septal and lateral mitral annulus, and strain imaging in all patients at rest in the left decubitus position. The changes in echocardiographic parameters in living liver donors were analyzed. Paired T-test was used to assess significant differences. Results The left ventricular (LV) global longitudinal strain (GLS), right ventricular (RV) GLS, and RV free wall LS, reservoir phase of left atrial strain (LAS-r), conduit phase of LAS (LAS-cd) did not show significant changes after the operation (for all, p>0.05). However, the absolute atrial contraction phase of LAS (LAS-ct) mean value increased significantly (14.2±8.8 vs 16.6±8.3, p=0.025) postoperatively. Among the conventional echo parameters, isovolumic relaxation time (IVRT) and the E/A ratio demonstrated notable postoperative alterations. The mean IVRT (87.3 ± 22.4 vs. 80.8 ± 18.1, p=0.014) and E/A ratio (1.5 ± 0.5 vs. 1.3 ± 0.3, p=0.012) exhibited a postoperative decline. Conclusions To the best of our knowledge, our study is the first to evaluate the effect of partial hepatectomy on cardiac functions by echocardiography in living liver donors, and there was no deterioration in the functions of both the ventricles and left atrium.

Liver transplantation currently represents a therapeutic option for patients with Wilson disease presenting with end-stage liver disease or acute liver failure. Indeed, it has been associated with excellent postoperative survival curves in view of young age at transplant and absence of recurrence. Attention has shifted over the past decades to a wise expansion of indications for liver transplantation. Evidence has emerged supporting the transplantation of carefully selected patients with primarily neuropsychiatric symptoms and compensated cirrhosis. The rationale behind this approach is the potential for surgery to improve copper homeostasis and consequently ameliorate neuropsychiatric symptoms. However, several questions remain unanswered, such as how to establish thresholds for assessing pretransplant neuropsychiatric impairment, how to standardize preoperative neurological assessments, and how to define postoperative outcomes for patients meeting these specific criteria. Furthermore, a disease-specific approach will be proposed both for the liver transplant evaluation of candidates with Wilson disease and for patient care during the transplant waiting period, highlighting the peculiarities of this systemic disease.

Cholestatic liver diseases, accompanied by the hepatic accumulation of bile salts, frequently lead to liver fibrosis, while underlying profibrogenic mechanisms remain incompletely understood. Here, we evaluated the role of extracellular pH (pHe) on bile salt entry and hepatic stellate cell (HSC) activation and proliferation. As modulators of intracellular pH (pHi), various proton pump inhibitors (PPI) were tested for their ability to prevent bile salt entry and HSC activation. Lastly, the PPI pantoprazole was employed in the 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC)-diet model of cholestatic liver fibrosis. We found in vitro, that slightly acidic pHe (7.2-7.3) enhanced bile salt accumulation in HSC and was a prerequisite to bile salt-induced HSC activation. Pantoprazole in the DDC model exhibited antifibrotic effects. We conclude that bile salt-induced activation of HSC may depend on the slightly acidic microenvironment present in the perisinusoidal space and modulation of pHi in HSC may offer a novel pharmacological target in cholestatic disease.

To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice.

Retrospective multicentrer cohort study.

Four Italian regions (Lombardy, Veneto, Lazio, Sardinia).

Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI).

Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use.

The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65).

The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients.

Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of "MELD purgatory," that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT.

In obese patients, metabolic dysfunction-associated steatotic liver disease is becoming a leading etiology of end-stage liver disease and HCC. Simultaneous liver transplantation and sleeve gastrectomy (LT-SG) have been proposed in the United States, but the safety and efficacy of the procedure have not been widely explored in Europe. Between January 2016 and December 2022, morbidly obese patients listed for liver transplantation at Tor Vergata University were enrolled in the LT-SG study. Primary outcomes were (1) safety expressed as 30- and 90-day overall survival and (2) major postoperative complications (Clavien-Dindo >IIIa). The secondary outcome was efficacy expressed as a 3-year %excess body mass index (BMI) loss. Eleven patients were enrolled in the study. The median BMI at transplantation was 42 (IQR 38-48). Indications of LT-SG were HCC (63.6%) and cirrhosis (36.4%). In 54% of cases, donors had high-risk characteristics (eurotransplant donor risk index >1.6). The 30- and 90-day overall survival were 63.6% and 54.5%, respectively. All deaths occurred in patients with P-SOFT >15 or in patients who had at least 3 of the following characteristics: >60 years, BMI >45, metabolic syndrome, MELD >25 or eurotransplant donor risk index >1.6. The 6 months, 1, 2, and 3 years %excess BMI loss was 73%, 60%, 50%, and 43%, respectively. LT-SG is a complex procedure that may carry excess risk in an unselected population. It should be considered only in highly selected patients. Standard donors are recommended, and prioritization of severely obese patients on the waiting list should be considered.

Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients.

The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence.

LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age.

Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes.

Ischemia reperfusion injury represents a significant yet difficult to assess risk factor for short- and long-term graft impairment in human liver transplantation (LT). As a non-invasive, non-ionizing tool, hyperspectral imaging (HSI) is capable of correlating optical properties with organ microperfusion. Hence, we here performed a study of human liver allografts assessed by HSI for microperfusion and prediction of initial graft function.

Images of liver parenchyma of 37 human liver allografts were acquired at bench preparation, during normothermic machine perfusion (NMP), if applicable, and after reperfusion in the recipient. A specialized HSI acquisition software computed oxygen saturation (StO2), tissue hemoglobin indices (THI), near infrared perfusion indices (NIR), and tissue water indices (TWI). HSI parameters were analyzed for differences with regard to preservation technique, reperfusion sequence and presence of early allograft dysfunction (EAD).

Organ preservation was performed by means of NMP (n = 31) or static cold storage (SCS; n = 6). Patients' demographics, donor characteristics, presence of EAD (NMP 36.7% vs. SCS 50%, p = 0.6582), and HSI parameters were comparable between both groups of preservation method. In organs developing EAD, NIR at 1, 2, and 4 h NMP and after reperfusion in the recipient was significantly lower (1 h NMP: 18.6 [8.6-27.6] vs. 28.3 [22.5-39.4], p = 0.0468; 2 h NMP: 19.4 [8.7-30.4] vs. 37.1 [27.5-44.6], p = 0.0011; 4 h NMP: 26.0 [6.8-37.1] vs. 40.3 [32.3-49.9], p = 0.0080; reperfusion: 13.0 [11.5-34.3] vs. 30.6 [19.3-44.0], p = 0.0212).

HSI assessment of human liver allografts is feasible during organ preservation and in the recipient. NIR during NMP and after reperfusion might predict the onset of EAD. Larger trials are warranted for assessment of this novel technique in human LT.

Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT.

This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion.

A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p = 0.012), and the incidence of early allograft dysfunction (EAD) (p = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045).

An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.

Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations.

The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached.

A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk.

The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol-related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation.

From 1990 to 2015, all patients transplanted for ALD were included.

A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years.

Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non-modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD.

To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH).

The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models.

We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness.

Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation.

What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients?

We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center. The study included patients admitted between January 1, 2010, and May 31, 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalization and at 1 year, admission to the ICU, and risk of pneumonia with Pseudomonas aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P aeruginosa.

We analyzed data from 403 hospitalizations of 333 solid organ recipients. In > 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than one-half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at 1 year postevent (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring 1 year after admission. Early blood cultures and bronchoscopy in the first 24 h significantly increased the odds of establishing an etiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonized patients, mostly lung transplant recipients.

This comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasizes the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients.

To review the current indications for liver transplantation (LT) in cirrhosis, including evolving criteria for hepatocellular carcinoma (HCC) and other malignancies, how donor organ allocation is established, and to address challenges of long-term complications post-transplantation.

A comprehensive review of the literature was conducted to evaluate advancements in LT indications, pretransplant evaluation protocols, organ allocation strategies, and management approaches for long-term post-transplant complications.

Liver transplantation remains the definitive treatment for cirrhosis and offers substantial survival benefits for patients with early-stage HCC. Recent advancements have expanded eligibility criteria to include patients with multiple comorbidities, advanced-stage HCC, and select malignancies, provided they meet specific selection criteria. The increasing demand for donor organs has driven innovations in donor pool expansion, which presents new challenges in recipient management, including the need for tailored pretransplant workups and strategies to mitigate long-term complications.

The field of liver transplantation continues to evolve, with broader indications and innovative approaches to donor pool expansion. These advancements necessitate careful patient selection, rigorous pretransplant evaluation, and effective long-term management strategies to optimize outcomes for transplant recipients.

Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival.

TransMet was a multicentre, open-label, prospective, randomised controlled trial done in 20 tertiary centres in Europe. Patients aged 18-65 years, with Eastern Cooperative Oncology Group performance score 0-1, permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer responsive to systemic chemotherapy (≥3 months, ≤3 lines), and no extrahepatic disease, were eligible for enrolment. Patients were randomised (1:1) to liver transplantation plus chemotherapy or chemotherapy alone, using block randomisation. The liver transplantation plus chemotherapy group underwent liver transplantation for 2 months or less after the last chemotherapy cycle. At randomisation, the liver transplantation plus chemotherapy group received a median of 21·0 chemotherapy cycles (IQR 18·0-29·0) versus 17·0 cycles (12·0-24·0) in the chemotherapy alone group, in up to three lines of chemotherapy. During first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) of 94 patients had received triplet regimens; 76 (80%) of 94 patients had targeted therapy. Transplanted patients received tailored immunosuppression (methylprednisolone 10 mg/kg intravenously on day 0; tacrolimus 0·1 mg/kg via gastric tube on day 0, 6-10 ng/mL days 1-14; mycophenolate mofetil 10 mg/kg intravenously day 0 to <2 months and switch to everolimus 5-8 ng/mL), and postoperative chemotherapy, and the chemotherapy group had continued chemotherapy. The primary endpoint was 5-year overall survival analysed in the intention to treat and per-protocol population. Safety events were assessed in the as-treated population. The study is registered with ClinicalTrials.gov (NCT02597348), and accrual is complete.

Between Feb 18, 2016, and July 5, 2021, 94 patients were randomly assigned and included in the intention-to-treat population, with 47 in the liver transplantation plus chemotherapy group and 47 in the chemotherapy alone group. 11 patients in the liver transplantation plus chemotherapy group and nine patients in the chemotherapy alone group did not receive the assigned treatment; 36 patients and 38 patients in each group, respectively, were included in the per-protocol analysis. Patients had a median age of 54·0 years (IQR 47·0-59·0), and 55 (59%) of 94 patients were male and 39 (41%) were female. Median follow-up was 59·3 months (IQR 42·4-60·2). In the intention-to-treat population, 5-year overall survival was 56·6% (95% CI 43·2-74·1) for liver transplantation plus chemotherapy and 12·6% (5·2-30·1) for chemotherapy alone (HR 0·37 [95% CI 0·21-0·65]; p=0·0003) and 73·3% (95% CI 59·6-90·0) and 9·3% (3·2-26·8), respectively, for the per-protocol population. Serious adverse events occurred in 32 (80%) of 40 patients who underwent liver transplantation (from either group), and 69 serious adverse events were observed in 45 (83%) of 54 patients treated with chemotherapy alone. Three patients in the liver transplantation plus chemotherapy group were retransplanted, one of whom died postoperatively of multi-organ failure.

In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases.

French National Cancer Institute and Assistance Publique-Hôpitaux de Paris.