Introduction: The Italian Ministry of Health has promoted a national screening program for Hepatitis C Virus (HCV) infections targeting individuals born between 1969 and 1989 who have never taken Direct Antiviral Agents (DAAs).Aim: To evaluate the effectiveness of this age-based screening in the referral area of ASST Papa Giovanni XXIII, Bergamo, with a focus on adherence, HCV antibodies (HCVab) positivity, HCV-RNA positivity, linkage to care, DAA introduction and achievement of sustained virological response (SVR). Materials and Methods. All individuals born between 1969-1989 who underwent HCV screening from May 2022 to June 2025 across four healthcare settings (hospital inpatient wards, outpatient blood collection centers, active screening invitation letter, and physician-initiated testing) were included. HCVab positive subjects were invited to undergo a confirmatory HCV-RNA test, hepatology consultation and ultimately DAAs initiation.Results: Among 23,577 screened individuals [15,594 responding to invitation letters, 4,913 during hospitalization, 2,014 via physician prescription, and 986 during blood collection], 308 (1.3%) tested positive for HCVab [0.8%, 3%, 0.9%, and 1.8% for each respective cohort]: 58% male, 48 (33-55) years-old, 17% of foreign origin. Overall, 49 (0.2%) patients had detectable serum HCV-RNA [0.07%, 0.67%, 1.04%, and 0.2%, respectively], while 259 individuals were HCV-RNA negative, of whom 51% had never received antiviral treatment. Notably, 200 (65%) HCVab positive subjects were already aware of their status, with 186 actively followed-up. Among the 49 HCV-RNA positive individuals [55% already known to have the infection], 24 (49%) started DAA reaching an SVR in 18, while the remaining 6 were non-compliant patients. The remaining 25 HCV-RNA positive patients (predominantly active drug users) never started DAAs due to non-adherence to follow-up visits.Conclusion: The impact of this screening program on the 1969-1989 birth-cohort population is low, thus suggesting an extension to advanced age groups and the implementation of more effective linkage-to-care strategies.

Introduction: Post-transplant lymphoproliferative disorders (PTLDs) represent a spectrum of potentially fatal neoplasms that can develop after liver transplantation (LT). Due to their rarity and heterogeneity, the incidence, clinical outcomes, and clinico-pathological features are not fully elucidated.Material and Methods: In this retrospective study, we reviewed a cohort of 1,908 LT recipients between 1999 and 2024: 730 pediatric patients and 1,178 adults. Only the cases PTLD developed after reaching adulthood were evaluated. The clinical-pathological variables included age, sex, underlying liver disease etiology, immunosuppressive regimens, tumor grading, donor and recipient Epstein-Barr Virus (EBV) status, and histopathological diagnosis.Results: Among the adult cohort, 19 cases of PTLD were identified (incidence 1,2%), 11 were males and 8 females, with a median age at diagnosis of 48 years. Notably, 4 (19%) of these cases involved patients who had undergone LT during childhood. The primary indications for LT were hepatitis C virus (HCV) infection (42.1%, n=8), primary sclerosing cholangitis (PSC) (21.6%, n=4), biliary atresia-associated secondary cirrhosis (15.8%, n=3), and fulminant hepatitis (10.5%, n=2). The median interval from LT to PTLD diagnosis was 94.2 months (1-204 months).Histopathological examination classified 18 cases as monomorphic PTLD (11 DLBCL). EBV activation was detected in 7 patients, suggesting a virus-related event in the pathogenesis. Regarding immunosuppressive therapy, 17 patients received tacrolimus with corticosteroids,two patients cyclosporine with corticosteroids. Following PTLD diagnosis, all patients underwent modifications to their immunosuppressive regimens; 10 patients discontinued tacrolimus, and 9 underwent a minimization of immunosuppression regimen. Therapeutic interventions universally included rituximab, with 8 patients additionally receiving CHOP chemotherapy. During follow-up, 2 (10,5%) patients died from PTLD, with mortality occurring at 4 and 12 months post-diagnosis.Conclusion: These findings suggest that PTLD, despite being an aggressive disease predominantly affecting young individuals, can be treated. In light of the availability of new cellular therapies, it would be important to continually explore the integration of EBV-targeted approaches A noteworthy aspect of this series is the etiology leading to LT. HCV infection, a well-known risk factor for hematological malignancies, was the pre-dominant underlying disease. The high frequency of PSC and fulminant hepatitis among patients developing PTLD underscores the potential impact of immune dysregulation mechanisms, although the precise disease pathways are not yet fully understood. Overall, this study highlights the importance of vigilant monitoring for PTLD in LT recipients, particularly those with HCV- or autoimmune related disease and underscores the need for further research into its pathogenesis and optimal management strategies

Background: chronic exposure to immunosuppressants may accelerate aging in ways not reflected by chronological age. Frailty may be considered a surrogate of biological age and can be assessed using a multidimensional frailty index which explores various deficits across liver function, functional status, cognition, comorbidities and physical performance. AIMS: to assess the multidimensional frailty of adult liver transplant (LT) recipients surviving longer than 20 years compared with the results obtained in the general population of similar age and gender, and to assess the impact of frailty on Quality of Life (QoL).Methods: we conducted a multicenter, cross-sectional prospective study comparing frailty and QoL of LT patients transplanted before 01/01/2005 and in regular follow-up at different LT Centers across Europe (Milan Niguarda, Padua, Milan Policlinico; Bergamo, Bucharest, Montpellier, Valencia, Tubingen, andRome San Camillo), with a control group of non-transplanted subjects of similar age, enrolled in geriatric or hepatological clinics. Frailty was assessed using a revised version of the Frailty Index (FI-39), now called ELITA FI-35, which is calculated as the ratio of the number of health deficits found in the single patient over the total number of potential deficits, that is 35. QoL was assessed with an auto-administered questionnaire, the EQ-5D-5L.Results: from April to November 15th 2025, 350 LT long-survivors’ patients and 80 controls, were enrolled. We present in this abstract the interim analysis on the first 99 cases and 41 controls enrolled until June 30th, 2025.Median (IQR) ELITA FI-35 in LT recipients was 0.26 (0.17-0.31) vs. 0.14 (0.11-0.20) in the control group (p <0.001) Fig1. A linear correlation was found between age and ELITA FI-35 both for the LT and for the control group (Fig.1), showing a progressive increase of the score in both group while age increase (Fig.2). This difference was significant only for the LT group (age<65: 0.14 [0.11, 0.18]; 6575: 0.29 [0.23, 0.31], p<0.001). Beyond liver function, the largest differences between cases and controls were observed in physical performance and cognitive domains, particularly: need for help with housekeeping (14% vs. 0%, p=0.03), balance disorders (20% vs. 5%, p=0.04), memory complaints (24% vs. 7%, p=0.4), and insomnia (32% vs. 12%, p=0.03). However, no significant differences were found in QoL measured by the EQ-5D-5L (median [IQR]: 78 [65–85] in LT patients vs. 75 [70–85] in controls, p=0.793), nor in emergency hospital admission rates (30% vs. 20%, p=0.272).The final analyses on the entire population are ongoing.Conclusion: long-term LT recipients showed a higher frailty burden than controls, especially in physical and cognitive domains, with frailty increasing significantly with age. Nevertheless, similar QoL scores between the 2 groups indicate that LT recipients maintain a preserved perception of well-being.

Background: Pediatric Liver Transplantation (PLT) usually shows excellent long-term outcomes. However, data regarding the quality of life (QOL) of these patients during the transition to adulthood are still limited.Methods: Between September 2017 and September 2025, 130 consecutive PLT recipients were evaluated at the pediatric-adult transitional care clinic of our Center. Transplant characteristics and complications were recorded. Psychosocial aspects and QOL were assessed through in-person interviews conducted during the scheduled clinical and psychological evaluations, using a modified and tailored WHOQOL-BREF questionnaire. Patients’ follow-up was defined until death or at September 30, 2025.Results: Patients were more frequently males (55.4%), with a median age at PLT of 17.7 months (2.8-216.3). A total of 109 patients (83.8%) received a split-graft, 21 patients (16.2%) a whole-liver. Major indications for LT were biliary atresia (60.0%), acute liver failure (6.2%) and metabolic-related liver disease (5.4%). At the end of transition (median age 19.2 years), 66.9% of patients were not hospitalized in the past 3 years; 57.7% had no comorbidities and 25.4% developed post-transplant food allergy. The backbone of maintenance immunosuppressive therapy consisted of tacrolimus in 127 patients (96.9%); 36.9% of patients were on only one medication daily, and 35.4% were on 2 per day. Complete autonomy in managing therapy was reported by 67.7% of patients, 20% still required parental supervision, 12.3% were dependent on their parents; 83.1% of patients reported excellent adherence to therapies. Patients were of normal weight in 66.2% of cases (BMI), underweight in 15.4%, overweight in 18.5% (only 2 cases of obesity); 48 patients (36.9%) regularly practiced sports. Smoking was reported by 16.2% of patients (3.8% electronic), whereas 80.8% reported complete abstinence from alcohol. In our cohort, 9 patients (6.9%) left school before completing secondary education, 70 (53.9%) were still attending secondary school, while 51 (39.2%) had obtained a high school diploma; among the latter, 31 patients were attending a university course. Thirty-eight patients were employed (24 while studying), whereas only 15 patients were neither studying nor working. At the end of the transition, 82.3% of patients reported a perceived QOL of good or better. At the end of the follow up (median post-LT 19.4 years), 117 patients were alive, 11 patients were followed at other Centers while 2 patients died. Nineteen patients had undergone re-LT (14.6%). Graft-survival rates at 1, 5, 10 and 20 years after LT, were 93.8%, 92.3%, 90.6% and 82.8%; patient-survival rates at 10 and 20 years after LT were 100% and 99% respectively.Conclusions: This study shows that, in addition to excellent patient survival outcomes, PLT recipients properly included in a “structured transitional protocol” usually achieve adequate integration into academic and professional life and perceive a good QOL.

BACKGROUND:The combination of hepatitis B immunoglobulin (HBIG) and high-barrier nucleos(t)ide analogues (hbNUCs) is widely considered the standard of care for preventing hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, clinical practices in Italy remains heterogenous, particularly regarding HBIG dosage, administration intervals, formulation choice, and selection of patients eligible for hbNUCs monotherapy or short-course HBIG regimens. This modified Delphi panel aimed to characterize current Italian practices for HBV prophylaxis after LT, focusing on patient risk stratification and HBIG management. METHODS:Sixteen Italian experts from EPAteam network participated in the three-round modified Delphi panel. After defining key clinical questions, a 35-item online survey was conducted. Any item with <66% agreement was designed as "controversial." Survey results and controversial topics were reviewed in a final in-person consensus meeting. RESULTS:All the sixteen panelists completed each Delphi round. There was agreement that the combination of hbNUCs and HBIG constitutes the standard HBV prophylaxis after LT. Patients with HBV-DNA >20,000IU/mL at LT and those with hepatitis D virus (HDV) coinfection were identified as high-risk for HBV recurrence and deemed candidates for life-long HBIG. No consensus was achieved on the optimal duration of prophylaxis for low-risk patients, nor on specific HBIG dosage and administration intervals for either risk group. Subcutaneous formulation was preferred for older patients without caregivers, frequent travelers, and those with coagulopathy. CONCLUSIONS:This modified Delphi panel confirmed that life-long combination of HBIG and NUCs remains the gold standard for the HBV prophylaxis after LT. Significant variability persists in clinical practice. Prophylactic strategies, especially in low-risk patients, are largely determined on a case-by-case basis, guided by patient characteristics rather than standardized protocols.

Background: in Europe, liver transplantation (LT) for acute liver failure (ALF) is reported to be about 8% of all LT. In Italy, LT for ALF has a national priority but few data are available. Within North Italy Transplant program (NITp) area, 9 out of 22 liver italian transplant centres perform about 40% of all LT in Italy. Aim: aims of this study were to evaluate: i) the characteristics of patients transplanted for ALF; ii) the etiologies of ALF and the trends over time taking into account the introduction of mandatory HBV vaccination for newborn and 12-year-old, in Italy, in 1991; iii) post-transplant survival.Methods: we retrospectively analyzed all pediatric and adult recipients who underwent a LT for ALF from the beginning of the activity (1988) to 2024 in the NITp area. Three different periods (1988-2000), (2001-2012), (2013-2024) were also considered to compare HBV to non-HBV ALF. ALF diagnosis was based on specific criteria defined by the National Super-Emergency Protocol (revised on May 15, 2024). Patients with acute-on-chronic liver failure or ALF due to HBV reactivation were excluded.Results: in NITp area, in the period 1988-2024, 356 patients received a LT for ALF. Of them, 294 (82,6%) were adults (161F/133M) and 62 (17,4%) pediatrics (28F/34M). Overall ALF HBV-related were 32,6%, all adult patients except 2 pediatric patients (age range: 15-69 yrs.; median age: 41.7 yrs). Non-HBV related ALF were 67.4% (age range: 0-71 yrs.; median age 33yrs). Etiologies of non-HBV related ALF were: undetermined (42,2%); DILI (8%); autoimmune (7%); mushroom poisoning (5.7%); Budd-Chiari syndrome (2.8%); liver trauma (1.7%).Dividing patients into the three different periods, statistically significant differences were recorded in HBV ALF for a progressive increase of recipient’s age (33 vs 47 years, p<0.001), a reduction in transplant need among younger subjects (51.6% vs 17.1%, p=0.006) and the percentage of foreign-born LT recipients starting from the 2001-2012 period ove r time (0 vs 40%, p=0.002). No differences in the ALF LT total number or HBV/non-HBV ratio were recorded.Overall re-transplantation (re-tx) rate was 10,1% (88.9% early re-tx) with no significant differences between HBV and non-HBV ALF (HBV vs non-HBV, respectively, 12% vs 9%; p= n.s.). Preliminary (post-transplant follow-up available for 309/356 patients) overall patient survival at 1, 3 and 5 year was: 69.9%, 63.9% and 62.6%, respectively.Conclusions: in the NITp area the need of LT for ALF did not change over time despite the introduction of mandatory HBV vaccination probably because of the rise in foreign-born recipients. ALF is a super-urgent indication with a national priority. Transplanted patients, despite re-tx rate, has a high survival rate.

Despite recommendations from scientific societies that hepatitis B immunoglobulin (HBIG) can be safely discontinued, centres across Europe continue to use the combination nucleoside analogues (NAs) plus HBIG for long‐term prophylaxis against hepatitis B virus (HBV) recurrence after liver transplant (LT). The aim of this study was to evaluate the safety of HBIG withdrawal in a cohort of LT recipients on long‐term HBIG+NAs. All patients under third‐generation NAs + HBIG and who adhered to the INSIGHT‐B protocol were followed up after HBIG withdrawal, in a multicentre, prospective, Italian cohort study, to evaluate the risk of HBV reactivation. The probability of HBsAg reappearance after HBIG withdrawal, stratified by presence of HCC at LT, was estimated through Kaplan–Meier curves and Log‐rank tests. Between February 2021 and January 2024, 222 liver transplant (LT) recipients withdrew HBIG 11.6 (IQR 6.7–17.0) years after LT and were followed up for a median time of 24 months. After HBIG withdrawal, Hepatitis B surface antigen (HBsAg) reappearance was observed in 12 patients (5.4%) with a cumulative 1‐, 2‐ and 3‐year recurrence rate of 4.08%, 5.36% and 6.89% respectively. HBsAg serum levels remained very low over the entire period of observation (median 9 months, range 3–20), and in four cases fluctuated around the detectability threshold. In all cases, HBV‐DNA persisted undetectable, liver function tests (LFTs) remained within the normal range, and neither HBV‐related hepatitis nor HCC were observed. No baseline patients' features were found to be significantly associated with the likelihood of HBsAg reappearance after HBIG withdrawal, including the presence of HCC at transplantation. HBIG could be safely withdrawn in HBV mono‐infected LT recipients on long‐term combination HBIG plus third generation NAs.

The Stanford Integrated Psychosocial Assessment for Transplant is a standardized psychosocial assessment recently used at ASST Papa Giovanni XXIII for the assessment of patients under evaluation for liver transplant. Currently, we are presenting a qualitative analysis of the initial group of patients under evaluation with this model. Our goal is to expand the analysis to all our patient population, and therefore to proceed with a quantitative analysis of the variables monitored: incidence of pre-liver transplant risk factors, comorbidities with or without other psychiatric disorders, presence/absence of alcohol and/or substance use disorders, social background, and neuropsychological screening.

IntroductionTransjugular intrahepatic portosystemic shunt (TIPS) placement after liver transplantation (LT) has been reported in a limited number of studies, with controversial results. Prognosis of these patients is still unclear. This study aims at evaluating both long-term graft-/patient-survival and which patients could eventually benefit from this procedure in the post-LT settingMethodsPatients who underwent TIPS for post-LT portal hypertension- or venous-related complications in our two Italian Transplant Centers were retrospectively evaluated. Clinical success was defined according with “SIR Quality Improvement Guidelines for TIPS”. Patients’ follow-up was until death or June 30th 2023.ResultsBetween 2002 and 2021, 74 patients underwent TIPS insertion after LT. Patients were more frequently males (77.0%), with a median age at LT of 52 years (range 18-69) and predominantly viral etiology (74.3%). TIPS was performed after a median time of 11 months (0.6-154) following LT. More frequent indications were: Refractory Ascites (44.6%), Sinusoidal Obstruction Syndrome-related ascites (31.1%), high-risk Gastroesophageal Varices (9.5%) and Portal Vein Thrombosis (6.8%). Recurrence of cirrhosis at the time of TIPS was documented in 30 patients (40.5%). Mean pre-TIPS MELD-score was 13.4±4.4; mean Porto-Systemic pressure Gradient was 15.2±5.4 mmHg pre-TIPS and 6.9±2.9 mmHg post-TIPS. Clinical success was achieved in 57 patients (77.0%). During the follow-up, 26 patients (35.1%) developed at least one episode of encephalopathy; shunt stenosis/occlusion was recorded in 19 patients (25.7%). Median follow up was 47.9 months (0.13-262). Graft- and patient-survival rates at 1, 3 and 5 years post-TIPS were 72.8%, 51.4%, 39.6% and 76.8%, 62.6%, 50.1% respectively. Graft-survival rates were significantly better in patients with age at TIPS <65 years, a time OLT-TIPS <12 months, a pre-TIPS MELD<15 and in patients without cirrhosis recurrence and a pre-TIPS SOS-related refractory ascites.ConclusionsPatients undergoing TIPS insertion after LT showed a 5-year graft-survival post-TIPS of nearly 40%; patient selection can improve survival rate to 65%.

The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient’s overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors’ and recipients’ risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.

BackgroundIn pts with ALD and ACLF a clear characterization of bacterial (BI) and fungal infections (FI) and their impact on survival is still lacking.Aimsto define prevalence and characteristics of BI/FI and their influence on survival and liver transplant need in a population with ACLF and alcoholic cirrhosis(AC).Materials and methods62 pts with ACLF and AC were consecutively admitted at our center from Jan 2016 to Jan 2023. Data on BI and FI were recorded at diagnosis and during hospitalization.Results36 patients at admission (58% of the whole population) presented with FI (5-13.9%) or BI (31- 86.1%). In 6 cases (16.6%) infections coexisted with AH. The distribution of the infection site and identified pathogens is shown in Figure 1. FI were severe, with 2 cases of Aspergillus pneumonia and 3 invasive Candidiasis. Also pts with a suspicious BI were treated. Piperacillina/tazobactam was the most frequent first-line empirical treatment (31 pts -56.5%).A switch to targeted therapy was necessary in 18 pts (58%);antifungal therapy was always targeted. A severe ACLF (grade II or III) was more frequent in infected patients (group A) compared to the others (group B - 72% vs 50%; p=0.07). At OLT, 8 (61.5%) among gA had an ACLF grade 2 or 3 (vs 3- 42.8% gB; p = 0.42).29 pts (46.7%) died, 20 in gA (55.6%) and 9 in gB (34.6%; p=0.10; OR gA/gB 2.36). The OLT free survival was 48 days in gA vs 56 days in gB; p=0.20. None of the pts with MDRO/FIs before transplant had a recurrence of the same pathogen after OLT.Conclusionsour study suggests the tendency to a worse outcome in infected patients. The prevalence of combined MDRO plus FI was high (30.5%). Among the recipients with MDRO/fungal before surgery, none showed a recurrence of the same pathogens.

BACKGROUND:Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM:We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS:In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS:From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS:Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.