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%.

MethodsThree LT types are included according to the donor: standard Deceased Brain Donors (DBDs); Deceased Cardiac Donors (DCDs); high-risk DBDs; Living donors (LDs). The data collection (retrospective/completed or prospective/ongoing includes [high volume (>65 LTs/yr) and intermediate-volume (≤65 LTs/yr)]. Each Center enrolled a fixed number of LT to minimize Center-volume bias.ResultsThe retrospective data consists of 3,884 LT from 2017 to 2019. There were 2958 (76.2%) standard DBDs, 797 (20.5%) DCD & amp; high-risk DBDs, 129 (3.3%) LDs. We stratified the cases into 5 geographical areas (Fig. 1A): Italy (N=1,766); Europe except-Italy (N=936); Asia-Oceania (N=496); North-America (N=377); South-America (N=309). Among the 53 LT centers of the retrospective cohort, there were 27 high-volume centers and 26 intermediate-volume centers). Italy and Asia had the larger adoption of machine perfusion, while DCDs were prevalent in Europe and North-America. Extended Criteria Donors (ECD) were mainly performed in Italy and North-America. Italy shows the highest donor age followed by Europe except Italy, North-America, South-America and Asia-Oceania. The mean recipient age was similar in all the areas, with a prevalence of hepatocarcinoma in Italy (Fig. 1B). The differences in the prevalence of other indications are summarised (Fig. 1C).ConclusionsThe analysis of IMPROVEMENT data depicts a screenshot of global liver transplant activity, never done before. Differences are due to epidemiological and logistic factors. The prospective data (ongoing) will provide more accurate information.

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.

IntroductionAlthough compulsory hepatitis B virus (HBV) vaccination greatly reduced new hepatitis D virus (HDV) disease in native Italians, migratory flows from HDV endemic areas are increasingly reconstituting the reservoir of this infection in Italy.AimTo report the preliminary results of a survey on the epidemiologic, virologic and clinical features of contemporary HDV cases in Italy.Materials and MethodsConsecutive patients positive for hepatitis B surface antigen (HBsAg) and antibodies to HDV (anti-HD) referred to 27 third-level Italian Centers were prospectively enrolled from August 2022 to October 2023.ResultsA total of 497 patients positive for anti-HD were recruited; median age was 56 (IQR 45–62) years and most patients were male (62.2%). Native Italians were 298 (60.0%). Among patients born abroad, the majority (n=166; 86.5%) were from Eastern Europe, followed by Africa (n=19; 9.9%) and Asia (n=4; 2.1%). Native Italians were older (median age 60, IQR 56–64, years vs. 44, IQR 37–51 years in patients born abroad; p<0.001) and had a more advanced liver disease (cirrhosis: 64.2% vs 51.1%; p=0.005; HCC: 14.5% vs 1.6%; p<0.001; liver stiffness: 12.0, IQR 7.9–18.5 kPa vs 9.2, IQR 6.3–14.4 kPa, p=0.001) compared to patients born abroad. One-hundred-thirty-three patients underwent centralized serum HDV-RNA assessment (RoboGene®v2) and HDV genotyping (direct sequencing). Overall, 103 (77.4%) patients were HDV-RNA-positive (median 5.26, IQR 4.03–6.04 Log IU/mL). The prevalent genotype was HDV-1 (n=100); 3 patients were infected with HDV-5. HDV-RNA correlated with ALT values (rs=0.303, 95%CI 0.105–0.484; p=0.004) and HDV-RNA-positivity was significantly associated with liver cirrhosis (OR=3.03, 95%CI 1.14–8.07; p=0.027).ConclusionsIn Italy, patients born abroad accounted for nearly half of the overall HDV infections collected in the past year. Most patients had advanced liver disease with high levels of serum HDV-RNA. These preliminary findings confirm that HDV infection in migrants represents an increasing medical alert in Italy.This research was supported by Gilead Sciences, Inc (study ID: IN-IT-980-6382).

BackgroundOLT is an effective option in ACLF, AH and sAH. However, is still unclear how many patients with a potential indication, can eventually access this option.Aimsto evaluate the real access rate of waitlisting for liver transplant and the rate of recurrence of alcohol use disorder (AUD) after OLT in pts with ACLF and ALD.Materials and methodsWe retrospectively analyzed 62 patients with ACLF and ALD admitted at our center from Jan16 to Jan23. The following scores were used to assess patient status at baseline and during fup: MELD-Na, Maddrey DF, GAHS, ABIC, Lille, Child-Pugh, CLIF-ACLF, CLIF-SOFA. Alcohol relapse after OLT was defined by the presence of signs/biochemical alterations associated with heavy alcohol use.ResultsThe clinical characteristics of the population are summarized in Table 1. 57 pts (92%) were potentially transplantable for age. 19 pts (31.6 %) were waitlisted or experienced a change in UNOS priority after the development of ACLF. 3 patients (4.8%) were already waitlisted maintaining an unmodified UNOS status after ACLF development.40 pts (66.6%) were never waitlisted: the most common reasons for ineligibility are shown in Table 2. Overall 20 pts were transplanted. Among them, the prevalence of AUD was relevant (7 pts-35%). During follow-up, 6 recipients (30%) experienced alcohol misuse after a median time of 1019 d [410-1564 d]; 2 pts (10%) developed ALD and died of liver failure.ConclusionsOLT represents an effective option in pts with ACLF and ALD. However, the access to waitlist is very limited mostly because of multiple active substances abuse and inadequate psychosocial profile. The recurrence of alcohol abuse was more frequent in pts without AUD at admission. The involvement of addiction center specialists in post-LT follow-up might be enforced as a potentially protective action against alcohol abuse.

BackgroundPatients with ACLF superimposed to alcoholic cirrhosis (AC) represent a peculiar subpopulation characterized by hampered access to OLT, potentially risk of graft failure due to alcohol use relapse and increased susceptibility to infections. Aims: To assess the evolution of ACLF superimposed to alcoholic cirrhosis (AC), need for critical care, transplantation and survival rates.Materials and methodsThe clinical data of 62 patients with ACLF and AC admitted at our center from Jan16 to Jan23, were retrospectively analyzed. The following scores were adopted to assess patient status: MELD-Na, Maddrey DF, GAHS, ABIC, Lille, Child-Pugh, CLIF-ACLF, CLIF-SOFA. Patient's eligibility for transplantation were routinely evaluated by a multidisciplinary team.Resultsthe clinical characteristics of the population are summarized in Table 1. The majority of patient (54 - 87%) presented with an identifiable trigger, with bacterial infections being the most common, followed by acute alcoholic hepatitis. 6 pts (9.6%) presented with both infection and AH. ACLF grades at presentations were: 34% ACLF-1, 37% ACLF-2, 29% ACLF-3.29 pts (47%) showed a rapid and positive response to the first line treatment, while 14 (23%) remained stable and 19 (30%) worsened. 20 pts (32%) were admitted at ICU/HDCU with the following median scores: CLIF-ACLF score 61 [52-65]; CLIF-SOFA 13 [IQR 12-14]; Meld 29 [26-35]. Seven pts (37%) needed continuous renal replacement therapy (RRT); 14 pts (74%) needed major vasopressor support; 10 patients underwent orotracheal intubation (OI) both for lung failure (7 pts- 37%) or severe HE (3 pts-15%).20 patients (32%) were transplanted, with the following condition severity at the time of OLT: 33% no ACLF, 6% ACLF-1, 28% ACLF-2, 33% ACLF-3. 29 patients died during follow-up (47%), 7 of which after OLT (35%). No deaths were observed in waitlisted patients while 2 recipients (10%) died in the immediate post-operative period. OLT-free survival at 1 year was very poor (20%), while overall survival (OS) at 1 and 5 years in transplanted patients was 90% and close to 60%.ConclusionsOLT represents an effective therapeutic option in patients with ACLF and alcoholic cirrhosis, with most patients showing an improvement in survival after OLT despite the severity of the condition at the time of transplantation. However, OLT is not a viable option in most of such patients due to the presence of severe psychosocial contraindications, frequently associated with AUD.

Background and AimsSevere thrombocytopenia [platelet count (PLTs) <50,000/µL] poses challenges in management of patients with chronic liver disease (CLD). Recently, thrombopoietin receptor agonists, such as lusutrombopag, have been developed to obviate the need for platelet transfusions. Existing real-world data are limited to sporadic reports or administrative databases. We aimed to assess the first post-marketing real-world European cohort of cirrhotic patients treated with lusotrombopag to verify the efficacy and safety of the drug.MethodIn the REAL-world lusutrombopag treatment in Italy (REALITY) study, we collected data from consecutive cirrhotic patients receiving lusotrombopag before invasive procedures between March 2021 and March 2023 from 19 Italian hepatologic centers, mostly affiliated with the “Club Epatologi Ospedalieri” (CLEO). Efficacy, defined as the ability of lusutrombopag to raise PLTs to ≥50,000/µL and avoid transfusions, as well as treatment-related adverse events, were recorded and analyzed.Results73 patients were enrolled (Table 1). Twelve patients (16%) had a previous medical history of portal vein thrombosis. Chronic viral hepatitis was the most common cause of CLD (55%), and endoscopic band ligation (38%) was the most common procedure performed (27%). Lusutrombopag induced a significant increase in PLTs [from 37,000 (33,000-44,000/µL) to 58,000 (49,000-82,000), p<0.001]. The efficacy of lusotrombopag was 74%. Logistic regression analysis (Table 2) identified baseline platelet value as the only independent factor associated with the response (OR 1.13, CI 95% 1.04-1.26, p 0.01) and with an adequate discriminative ability (AUROC of 0.78). Notably, we identified the baseline PLTs ≤29,000/µL as the threshold for identifying patients unlikely to respond to the drug (sensitivity 91%). Finally, de novo portal vein thrombosis was observed in 4 patients (5%).ConclusionIn this initial real-world European series of CLD, lusutrombopag demonstrated efficacy and safety consistent with findings from registrative trials. According to our results, patients with baseline platelets ≤29,000/µL are unlikely to respond to the drug.

Background Primary sclerosing cholangitis (PSC) represents 5% of the indications for liver transplantation (LT). Recurrence of PSC (rPSC) is reported to occur in 8-27% and it has a great impact on both graft and patient survival. Methods the clinical data of 35 patients with PSC who underwent LT at our center in the last 20 years were retrospectively evaluated. Twentyfive were male (71,4%) with a history of IBD before OLT (67%). Tacrolimus+steroid was the most frequent immunosoppressive schedule (84.8%). Five patients (15.1%) underwent re-OLT (3 for rPSC, 2 for immunological damage). Graft and patient survival at 5 years were 73.6% and 88%. A female transplanted for the first time at the age of 17 years, redeveloped aggressive rPSC, with the need for a third LT. The time interval between second and third LT was much shorter than between the first and second LT (2015-2019-2021). In order to modulate the patient's immune reactivity, within 3 months from the 3rdLT, stem cell mobilization (cyclophosphamide+G-CSF) was performed, and CD34+ cells were selected: the patient eventually underwent autologous hematopoietic stem cell transplantation (aHSCT), preceded by a conditioning regimen (melphalan+rabbit antithymocyte globulin). In the immediate post-aHSCT, the patient experienced a E. Coli-related sepsis. The full immunosuppressive regimen was reintroduced 18days after aHSTC. Three and 14 months after aHSCT, she underwent follow-up liver biopsies which excluded rPSC and showed a picture of mild ectasia of centrolobular veins and pericentral sinusoids, associated with initial aspects of sclero-atrophy of the bile ducts, consistent with liver injury secondary to chemotherapy. Liver test were maintained normal. Conclusion ReLT is the only treatment option for aggressive rPSC. Our patient succesfully underwent 3rd R-LT combined with aHSCT with no evidence of rPSC at over 14 months follow-up: this may represent a successful approach as a preemptive strategy in selected cases of reLT for rPSC. Primary sclerosing cholangitis (PSC) represents 5% of the indications for liver transplantation (LT). Recurrence of PSC (rPSC) is reported to occur in 8-27% and it has a great impact on both graft and patient survival. the clinical data of 35 patients with PSC who underwent LT at our center in the last 20 years were retrospectively evaluated. Twentyfive were male (71,4%) with a history of IBD before OLT (67%). Tacrolimus+steroid was the most frequent immunosoppressive schedule (84.8%). Five patients (15.1%) underwent re-OLT (3 for rPSC, 2 for immunological damage). Graft and patient survival at 5 years were 73.6% and 88%. A female transplanted for the first time at the age of 17 years, redeveloped aggressive rPSC, with the need for a third LT. The time interval between second and third LT was much shorter than between the first and second LT (2015-2019-2021). In order to modulate the patient's immune reactivity, within 3 months from the 3rdLT, stem cell mobilization (cyclophosphamide+G-CSF) was performed, and CD34+ cells were selected: the patient eventually underwent autologous hematopoietic stem cell transplantation (aHSCT), preceded by a conditioning regimen (melphalan+rabbit antithymocyte globulin). In the immediate post-aHSCT, the patient experienced a E. Coli-related sepsis. The full immunosuppressive regimen was reintroduced 18days after aHSTC. Three and 14 months after aHSCT, she underwent follow-up liver biopsies which excluded rPSC and showed a picture of mild ectasia of centrolobular veins and pericentral sinusoids, associated with initial aspects of sclero-atrophy of the bile ducts, consistent with liver injury secondary to chemotherapy. Liver test were maintained normal. ReLT is the only treatment option for aggressive rPSC. Our patient succesfully underwent 3rd R-LT combined with aHSCT with no evidence of rPSC at over 14 months follow-up: this may represent a successful approach as a preemptive strategy in selected cases of reLT for rPSC.

neuropathic pain, mood stabilization, etc. Queries to the database are anonymous, the key information that is recorded is the country of origin.Results: During 51 months of follow-up, a total of 94, 695 queries from 98 countries were recorded by website users to check DDIs between eiAEs and DAAs.The most frequently requested DAAs were glecaprevir/pibrentasvir (GP; 23.3%) and sofosbuvir/velpatasvir (22.3%).Among the eiAEs, carbamazepine was the most frequently requested eiAE (37.9%) followed by phenytoin (19.9%) and oxcarbazepine (18.7%).Until recently, all of these combinations were contraindicated (red flag).On an individual level, the most frequently requested DDI between an eiAE and a DAA was carbamazepine & GP (n = 7, 773 queries).Conclusion: During our observation period, we received an average number of 1, 857 requests per month for a potential DDI between an eiAE and a DAA, demonstrating a huge demand globally for advice on concomitant use of these drugs.Our recommendations have recently been updated to reflect recent real-life data.Given the high number of DDI requests involving an eiAE and DAAs, we believe physicians should be informed that treatment options have now been improved, and HCV treatment should no longer be deferred when an eiAE is on board.

Introduction Discontinuation of hepatitis B (HBV) immune globulin (HBIG) after liver transplantation (LT) for HBV-related cirrhosis with and without hepatocellular carcinoma (HCC) represents a challenging option. The adherence to this option in real-life practice is unknown. Aim In a contemporary cohort of patients transplanted for HBV, with and without HCC, we aimed to; 1) assess the rate of HBV recurrence (HBV-R); 2) evaluate risk factors for HBV-R; 3) evaluate the association between HBV-R and HCC recurrence (HCC-R) and patient survival. Materials and Methods This is a multicentric, retrospective study designed by the "Permanent Transplant Commission" of the Italian Association for the Study of the Liver. All recipients who underwent LT for HBV cirrhosis were included. Exclusion criteria were: LT prior to January 1, 2010; age <18 years old; combined transplantation; HIV coinfection; duration of follow-up after LT <12 months. HBV-R was defined by positivity of HBV-DNA and/or HBsAg. Uni and multivariate linear regression analysis were used to identify predictors of HBV/HCC-R. Results 1115 patients were included. Indications for LT were HCC (51%), decompensated cirrhosis (41.2%), acute on chronic liver failure (ACLF) (3.4%), and acute liver failure (ALF) (4.2%). Life-long HBIG + nuclos(t)ide analogues (NA) was the most common used prophylaxis (94.4%). Overall rate of HBV-R was 2.2% (median time after LT: 7 months). Patients under life-long HBIG + NA had lower rates of HBV-R than those in whom HBIG were withdrawn and those who received NA alone (1.4% vs. 10.7% vs. 13.6%; respectively, p<0.001). HBV-R was associated with a lower survival after LT (p=0.008). In patients transplanted for HCC (n=535), the rate of HBV-R was 2.8% and of HCC-R was 10.3% (median time from LT: 17 months). Rate of HBV-R was higher in patients with vs. without HCC-R (14.6% vs. 1.2%; p<0.001). Multivariate analysis showed that HBV-R was the only parameter independently associated with HCC-R (HR: 20; CI95% 5-86; p<0.001). HCC-R was associated with a significantly reduced survival after LT (5-year survival 36% vs. 94%; p<0.001). Conclusion Life-long HBIG + NA is the most commonly used scheme for HBV-R prophylaxis after LT in Italy, leading to a low risk of HBV-recurrence. In LT recipients, HBV recurrence is associated with an increased risk of death. In patients transplanted for HCC, HBV-R is independently associated with HCC recurrence. Therefore, discontinuation of HBIG in these patients should be considered only in the setting of clinical trials