Background & Aim: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating complications of portal hypertension (PH) in patients with cirrhosis. However, there is a gap in the knowledge in patients with PSVD, being a rare condition. This study aimed to evaluate the efficacy and outcomes of TIPS placement in patients with PSVD. Methods Retrospective, multicenter study in patients with histologically confirmed PSVD undergoing TIPS across 27 centers worldwide. Demographic, clinical, and procedural data were systematically documented. Time-to-event outcomes were analyzed using Cox proportional-hazards models. Results The cohort comprised 260 patients, 64% males, median age 52 years (40-63), with 66% having associated conditions, predominantly hematological disorders. Nodular regenerative hyperplasia was the most common histopathological finding (33%). Pre-TIPS portal vein thrombosis (PVT) was present in 47%, with complete occlusion in 14%. Median MELD score was 9 (8-11).All patients received covered stents, dilated to 10mm (39%) or 8mm (36%). Median portal pressure gradient decreased from 19 mmHg (15-23) to 8 mmHg (5-11); 76.54% reached a PPG <12 mmHg.After TIPS positioning, 93.2% of patients undergoing TIPS for bleeding from varices did not experienced rebleeding, while ascites was controlled in 86.3%; additionally, 36.2% discontinued diuretics.Stent dysfunction occurred in 22.7%, with thrombosis making up 54.2% of cases. Pre-TIPS PVT did not predict stent thrombosis (p=0.089), but prothrombotic genetic disorders increased the risk of post-TIPS PVT (HR: 4.30, 95%CI 1.85-10.32; p=0.003). Cardiac failure was observed in 5.8% of cases, and liver failure in 1.2%.Overt hepatic encephalopathy (oHE) occurred in 24%, with pre-TIPS ascites being the only independent risk factor (HR:2.52, 95%CI 1.30-4.9; p=0.006). During follow-up [31 months (34-66)], 4.2% of patients underwent liver transplants, and 14.6% died, with only 7 deaths directly caused by liver disease. Transplant-free survival was 30 months (25–58), with 93.0% at 1 year and 77.9% at 5 years. In multivariate analysis, ascites control after TIPS (HR: 0.28, 95%CI 0.098-0.82; p=0.02), bacterial infection after TIPS (HR: 3.28, 95%CI 1.12–9.58; p=0.03), and hematological disorders (HR: 0.19, 95%CI 0.04–0.87; p=0.033) predicted transplant or death. For non-liver-related deaths, hematological disorders (HR: 2.2, 95%CI 1.02–4.9; p=0.04) and CKD (HR 3.6, 95%CI 1.4–9.4; p=0.008) were independent factors. Conclusions In this large cohort, TIPS appears to be effective in managing complications of portal hypertension in PSVD patients, despite a high rate of stent dysfunction. Multidisciplinary evaluation and customized risk assessment remain essential due to the significant influence of the associated conditions on survival.

Background-Aim: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease. Epidemiological data in Italy are limited. To address this the Italian PBC Registry was established in 2019 to collect retrospective and prospective data. This study provides an overview of the Registry and its collected data.Methods: The Registry is based on a centralized database collecting demographics, biochemistry, disease stage and treatments. Tests at diagnosis were defined as those performed 3 months before to 30 days after diagnosis; tests at 1 year after UDCA were those performed 11–15 months after treatment initiation. Categorical variables are reported as frequencies (%); continuous variables are reported as mean ± SD or median and interquartile range (IQR). ALP, AST, ALT, GGT are expressed as ratios of their ULN, bilirubin as mg/dL.Results: From 2019 to 2025 enrolment increased from 128 to 3310 (37±22 patients/month). 3199 were analyzed (111 excluded for missing data). The Registry involves 69 active centers, 61 entering data, distributed across Italy (40 North, 9 Center, 20 South/Islands). 2836 (89%) were female with mean age 55.3 ± 12 years, BMI 24.96 ± 4.64, 3067 (96.7%) were Caucasian. Median follow-up was 6.9 years [3.1, 12.6]. 2018 (80.3%) reported no alcohol consumption, 456 (18.1%) consumed < 10/20 g/day (women/men) and 40 (1.6%) consumed >10/20 g/day (women/men). 1724 (70%) never smoked, 423 (17.2%) were former and 315 (12.8%) were current smokers. Optional biological samples (blood, urine, stool, liver tissue) are collected; 13 centers collect blood annually (recruitment/follow-up): 422 patients provided one sample, 116 two and 105 three or more. At diagnosis, among 1840 patients (57.5%) with available tests, the mean values were: ALP 1.59 [1.07, 2.67], AST 1.25 [0.83, 2.10], ALT 1.32 [0.80, 2.18], GGT 3.90 [1.89, 7.49], bilirubin 0.65 [0.50, 0.92] mg/dL. AMA positivity was detected in 1241 (68.5%), while 243 (13.4%) were negative and 328 (18.1%) had not been tested. Liver biopsy was performed in 666 (20.8%) patients and transient elastography in 653 (20.4%) with a median liver stiffness of 6.6 kPa [5.0, 9.1]. After one year of UDCA 809 (25.3%) patients had: ALP 1.11 [0.78, 1.64], AST 0.78 [0.59, 1.06], ALT 0.70 [0.48, 1.10], GGT 1.26 [0.70, 2.78], bilirubin 0.60 [0.44, 0.83] mg/dL. Elevated ALP (>1.67) was observed in 185 (22.9%) patients. However, considering the entire cohort, 923 (28.8%) patients initiated second-line therapy: 429 (46.5%) with Obeticholic Acid (OCA), 277 (30%) with fibrates (bezafibrate/fenofibrate), 163 (17.7%) with combination therapy (OCA and fibrate). Regarding the new PPAR-targeted therapies, 125 (13.5%) patients initiated Elafibranor and 52 (5.6%) initiated Seladelpar.Conclusions: The Italian PBC Registry provides a national picture of PBC, supporting disease monitoring and management. Continued commitment from participating centers will enhance data completeness and strengthen the reliability of future analyses.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced hepatocellular carcinoma, increasing opportunities for downstaging and conversion to liver transplantation (LT) eligibility. However, the use of ICIs in the LT setting raises challenges regarding the optimal timing and duration of treatment, safety, and assessment of tumor response. Moreover, the use of ICIs for hepatocellular carcinoma recurrence after LT is associated with an increased risk of acute cellular rejection and potential graft failure. This article presents expert consensus guidance developed by a panel of 9 LT experts from the Permanent Transplant Commission of the Italian Association for the Study of the Liver (AISF) and conducted based on the modified Delphi method. Fifteen clinically relevant questions were developed through an iterative process involving structured literature review, clinical experience, and identification of practice gaps. Each question was assigned to 1 to 2 panel members with topic-specific expertise, who were responsible for performing a targeted literature review, drafting the evidence summary, and proposing a recommendation. Statements receiving >75% agreement in 2 rounds of voting were considered approved and presented in this article. Until prospective data become available, this guidance aims to assist clinical decision making within the evolving field of LT oncology.

Donation after cardiovascular determination of death (DCD) has expanded the liver donor pool but remains limited by concerns over prolonged donor warm ischemia and inferior outcomes, particularly in countries such as Italy where legally mandated asystolic periods increase donor risk. This study evaluates trends in DCD liver transplantation at a high-volume Italian center, to assess whether accumulated experience and advanced reconditioning strategies influenced outcomes over time. We retrospectively analyzed adult DCD liver transplants performed between 2016 and 2023. Donor characteristics, recipient risk profiles, perfusion strategies, ischemia times, and post-transplant outcomes were compared between an early (2016–2021) and a late (2022–2023) period. Temporal trends were evaluated using linear regression. Seventy-five DCD liver transplants were included. Later-period recipients had more advanced liver disease (39.1

Background:Kidney transplant recipients remain at high cardiovascular risk despite improved graft and patient survival. Physical inactivity, weight gain, and suboptimal dietary habits are common after transplantation and may contribute to this burden. Methods:The KT-LIFESTYLE trial is a pragmatic, multicentre, prospective, open-label randomized controlled study designed to evaluate whether a structured lifestyle intervention can reduce cardiovascular risk in kidney transplant recipients. Participants will be randomized 1:1 to individualized exercise prescription plus tailored dietary counselling or standard lifestyle advice. The intervention combines multidisciplinary assessment, individualized exercise programming, motivational interviewing, and nutritional counselling integrated into routine transplant follow-up. The primary endpoint is the change in 10-year cardiovascular risk, assessed by the Framingham score over 36 months. Secondary outcomes include renal function estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation estimated glomerular filtration rate, body composition, inflammatory markers, gut microbiota composition, health-related quality of life, adherence to physical activity and dietary counselling, hospital admissions, major adverse cardiovascular events, and all-cause mortality. Conclusions:KT-LIFESTYLE aims to provide evidence on the effectiveness and feasibility of a long-term lifestyle intervention after kidney transplantation. The study may also clarify the mechanisms through which lifestyle modification influences cardiovascular risk, inflammation, body composition, and gut microbiota in this population.Clinical trials registration number: NCT06806670.

Background Extended criteria donors (ECDs) have become an important source of organs, but their association with infection risk remains unclear. This systematic review assessed the impact of ECD versus standard criteria donors (SCDs) on infection rates in kidney and liver transplant recipients and analyzed the variability of ECD definitions.Methods Three different literature databases were searched up to June 2024 for randomized controlled trials or observational studies comparing infection rates between ECD and SCD recipients. Studies without quantitative data or comparator groups were excluded. Outcomes were measured at 30-180 days and 1, 3, and 5 years posttransplant, evaluating both bacterial and viral infections.Results A total of 11 119 articles were screened and 131 studies included. At 30 days, bacterial infections occurred at similar rates between ECD and SCD recipients (odds ratio [OR] 1.15, 95% confidence interval [CI] .86-1.53, P = .36). However, liver transplant recipients from ECDs had a higher infection risk (OR 1.73, 95% CI 1.12-2.68, P = .01). Definitions of ECD varied notably, especially in liver transplantation, while kidney transplantation criteria were more consistent.Conclusions Current evidence does not definitively establish a link between ECD and infection risk, highlighting the need for standardized donor definitions and routine reporting of infections as ECD outcomes.

Background and Objectives: Adult-onset cryptogenic cholestasis (AOCC) remains a diagnostic challenge. With the increasing use of Next-Generation Sequencing (NGS), variants in genes traditionally linked to paediatric cholestatic disorders are increasingly detected in adults. This study evaluated the diagnostic yield of a multigene panel and explored genotype–phenotype correlations in a large Italian AOCC cohort.METHODS:From February 2017 to May 2023, outpatients >14 years with AOCC were consecutively enrolled in four Italian tertiary centres. High-throughput sequencing covering up to 36 genes—including PFIC-related ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, VPS33B, MYO5B, KIF12, SEMA7A, SLC51A, USP53, VPS39, ZFYVE19—was performed. Variants were classified following ACMG criteria. Clinical, biochemical, and histological features were compared between patients with pathogenic/likely pathogenic mutations (P/LPMs) and those without, considering both the whole panel and PFIC genes alone. RESULTS: A total of 233 patients were analysed; median age at testing was 46 years (35.0–55.0), and 108 (46.4%) were male. Serum bile acids (8; 4.0–18.8 μmol/L), γ-GT (97; 43.0–187.0 IU/L), and alkaline phosphatase (127.5; 92.0–187.0 U/L) showed mild elevation. Liver stiffness values indicated absent or minimal fibrosis (5.3; 4.3–7.3 kPa). P/LPMs were detected in 45 patients (19.3%); 106 (45.5%) carried either P/LPMs or VUS. Frequently affected genes were ABCB4, TJP2, SLCO1B3, ABCB11, MYO5B, ABCC2, VPS33B, and ATP8B1.Patients with P/LPMs more commonly had intrahepatic cholestasis of pregnancy (ICP), early-onset cholelithiasis, LPAC, a family history of liver disease, younger age (<40 years) and higher bile acids (p<0.05). The rate of P/LPMs in PFIC genes across the entire cohort was 15.5% (36 patients). In this subgroup, subjects more often reported ICP, LPAC, early cholelithiasis and familial liver disease, were younger at testing, and had higher alpha-fetoprotein values (p<0.05).Two multivariate models were developed. In the first, male sex (OR 4.065; 95% CI 1.564–10.568; p=0.004), bile acids (OR 1.016; 95% CI 1.001–1.032; p=0.044) and early-onset cholelithiasis (OR 2.412; 95% CI 1.000–5.959; p=0.050) independently predicted P/LPMs in the cholestasis panel. In the second, focusing on PFIC genes, ICP (OR 5.313; 95% CI 1.788–15.783; p=0.003) and early-onset cholelithiasis (OR 3.163; 95% CI 1.422–7.032; p=0.005) were the only independent predictors. CONCLUSIONS: Variants in inherited cholestasis genes are frequent in AOCC and associate with distinct phenotypes, particularly early-onset cholelithiasis and ICP, largely involving PFIC genes. ABCB4 remains the most commonly implicated gene. Integrating NGS into diagnostic pathways may improve recognition of genetic cholestatic disorders in adult hepatology.

Normothermic regional perfusion (NRP) is increasingly implemented to optimize the outcome of transplantation from donors undergoing circulatory determination of death. NRP shortens the duration of warm ischemia, allowing splanchnic reperfusion with oxygenated blood. This supports the abdominal organs throughout recovery, allowing for their thorough assessment, avoids the need for rapid recovery, and restores a near physiological environment. However, after NRP, the grafts are exposed to a period of cold ischemia preceding further evaluation and reconditioning through ex situ machine perfusion or direct transplantation. The duration of cold ischemic time may be extremely variable. During cold ischemic time, the liver and the kidneys are indirectly protected by a decrease in metabolic demands induced by deep hypothermia. To optimize protection, the hypothermic state is initiated in situ, immediately after extracorporeal blood flow interruption, via topical cooling with sterile ice and intravascular cooling. The latter is usually induced by the administration of cold preservation solution (CPS) by gravity. We performed an observational study to assess the feasibility, safety, and effectiveness of a controlled strategy of CPS administration and oxygenation employing the NRP circuit and cannulae in controlled circulatory determination of death undergoing abdominal NRP. This approach provided a controlled, fast, and consistent flow, ensuring a prompt induction of hypothermia. Moreover, during CPS administration, the delivery of a fresh gas flow through the membrane lung resulted effective in significantly increasing the oxygen tension in the CPS. The hyperoxygenation of the blood-free perfusate might provide a metabolic substrate to the cells, preconditioning the grafts before cold ischemia.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibro-inflammatory lesions of the biliary tree. In the absence of available, effective medical therapies, many patients progress to liver failure, making PSC one of the leading indications for liver transplantation (LT), despite its rarity. While LT in PSC is associated with good overall short- and long-term survival, post-transplant outcomes are limited by recurrent PSC (rPSC), which affects up to one quarter of PSC recipients with a significant risk of graft loss and re-transplantation. The risk of rPSC reflects a complex interaction between donor and recipient factors including associated inflammatory bowel disease (IBD), and long-term exposure to immunosuppression. Therefore, post-transplant management requires an individualized multidisciplinary approach and tailored immunosuppressive regimens aimed at balancing the risk of rejection and rPSC with the risk of infection and malignancy. Optimal control of IBD has emerged as a key modifiable determinant of rPSC risk and post-transplant outcomes. In addition, patients with PSC, particularly PSC-IBD patients, carry a significantly increased risk of hepatobiliary and colorectal cancer. Importantly, this oncological risk persists after LT. Thus, long-term, structured cancer surveillance must remain an integral component of post-transplant care. Looking ahead, novel therapies targeting shared hepatic and intestinal fibro-inflammatory pathways are currently being investigated to modify disease activity in the pre-transplant setting. Future studies are needed to assess whether these agents might be applicable also in the post-transplant setting to improve long-term graft and patient survival.

BACKGROUND AND AIMS:Sarcoidosis is a rare systemic granulomatous disease involving the liver in up to 20% of cases. Data on hepatic sarcoidosis (HS) prevalence and management remain limited. This study aims to provide a comprehensive analysis of HS patients across Italy, focusing on diagnostic pathways, management strategies, and prognostic factors. METHODS:This multicenter retrospective study, conducted from April 2022 to December 2023, includes data from 36 hepatology units, affiliated with the Italian Association for the Study of the Liver (AISF), invited to analyse consecutive cases of HS reported between 2003 and 2023. RESULTS:A total of 78 patients with HS were identified, with complete data available for 58 (median age 53 years; 57% female; 81% Caucasian), prospectively followed for a median of 41 months. Pulmonary and lymphatic involvement were present in 45% and 34% of cases, respectively. Isolated hepatic involvement was seen in 10%. Liver biopsy revealed granulomas in all specimens. Histological cirrhosis and clinically significant portal hypertension (CSPH) were observed in 10% and 14% of patients, respectively. Patients with CSPH had a significantly higher body mass index (BMI) compared to those without (33 vs. 25, p = 0.002). Steroids and ursodeoxycholic acid were the first-line treatments for 80% and 28% of patients, respectively, while 29% required second-line therapies. One patient died from liver-related complications. CONCLUSIONS:This nationwide study underscores the variability in HS presentation and management across Italy. Liver biopsy remains essential for diagnosis and staging. While steroids are the primary treatment, many patients require second-line therapies. Our finding of a higher BMI in patients with CSPH suggests that metabolic factors may play a role in disease progression, warranting further investigation.

To identify a tumor-mean absorbed dose (Dmean) that can predict response to Yttrium-90 resin-microsphere transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC) and evaluate its efficacy and safety. Patients with HCC eligible for TARE in two centers between January 2020 and May 2024 were retrospectively analyzed. Clinical, radiological, and procedural data were collected. Objective response rate (ORR) on lesion, complete response (CR), overall response, time-to-local progression (TLP), and time-to-progression (TTP) were evaluated on contrast-enhanced CT at 3 and 6 months according to mRECIST. The optimal Dmean of ORR on the target lesion and of CR was identified with ROC analysis at 3-months. Fischer’s test compared ORR, Kaplan–Meier survival outcomes, and Cox regression was used for uni-and multivariable analyses. Seventy-six lesions in 64 patients (mean age 71.3 ± 9.6; 54 men) were evaluated. Median follow-up was 15.0 months (IQR 8.0–24.3). Mean tumor diameter was 55.2 (± 31.8) mm. CR on target lesion at 3-months was achieved in 42 lesions. Mean TLP and OS were 27.6 ± 2.5 and 36.2 ± 2.9 months, respectively. The calculated Dmean for ORR was 296.74 Gy (specificity 100, PPV 100

Background & Aims:Hepatocellular carcinoma (HCC) may develop in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) even in the absence of cirrhosis. Whether the risk of HCC in non-cirrhotic MASLD is substantial to justify surveillance, and which patients may benefit, remains unclear. Methods:Post-hoc analysis conducted on a prospective MASLD cohort. All participants underwent baseline liver stiffness measurement (LSM) using SuperSonic Imagine (SSI) two-dimensional shear wave elastography (2D-SWE) and were surveilled every 6-12 months. Exclusion criteria were less than 6 months follow-up, unavailable LSM-SSI, prior HCC. Primary outcome was HCC, with hepatic decompensation and portal vein thrombosis (PVT) as competing risks. To improve risk stratification, LSM-SSI optimized cut-offs were applied: <7.4 kPa to rule-out advanced fibrosis, ≥15.6 kPa to rule-in cirrhosis, based on recent meta-analytic data, and were integrated in different risk stratification algorithms. Results:Among 352 patients with a median follow-up of 31 (14.1-57.8) months, 257 (73%) had LSM-SSI <7.4 kPa, 67 (19%) between 7.4-15.6 kPa, and 28 (8%) ≥15.6 kPa. During follow-up, 9 (2.6%) developed HCC, 6 (1.7%) decompensation, 2 (0.6%) PVT. No events occurred in patients with LSM-SSI <7.4 kPa. In the 7.4-15.6 kPa group, HCC and decompensation occurred in 3 (4.5%) and 1 (1.5%), respectively. For non-cirrhotic patients (LSM-SSI <15.6 kPa), LSM-SSI was significantly associated with HCC risk (HR 1.542, p<0.0001). Following multivariate analysis, independent HCC predictors were: LSM-SSI (HR 1.052, 95% CI 1.030-1.075, p<0.001), type 2 diabetes mellitus (HR 4.555, 95% Ci 1.091-19.012, p=0.038), and gamma-glutamyl transferase (HR 1.004, 95% CI 1.001-1.006, p=0.003). A two-step non-invasive algorithm combining LSM-SSI and the PLEASE score yielded 100% negative predictive value and 89.5% accuracy in identifying patients for HCC surveillance. Conclusion:HCC is the leading liver-related complication in non-cirrhotic MASLD. LSM-SSI <7.4 kPa effectively excludes high-risk patients. A two-step algorithm further enhances risk stratification and surveillance precision.

BACKGROUND:The advent of machine perfusion (MP) has significantly improved post-liver transplantation (post-LT) outcomes, potentially enabling the use of increasingly marginal grafts and expanding the organ donor pool. METHODS:We present a retrospective cohort study of consecutive adult patients who underwent LT between 2018 and 2023 at a leading Italian institution. The objective was to evaluate outcomes following the use of hypothermic oxygenated perfusion (HOPE) in high-risk grafts. RESULTS:A total of 507 patients were included in the final analysis, of whom 420 (83%) received extended criteria donor (ECD) grafts. Among ECD grafts, 62 (15%) were from donation after circulatory death (DCD) donors, and 64 (15%) were previously discarded by other centers. HOPE was applied in 248 (49%) cases. Recipients in the HOPE group experienced significantly lower rates of early allograft dysfunction (EAD) (20% vs. 32%, p = 0.007), primary nonfunction (2% vs. 7%, p = 0.017), and severe postoperative complications (Clavien-Dindo grade ≥ 3b) (19% vs. 28%, p = 0.026). Notably, marginal grafts treated with HOPE achieved survival outcomes comparable to those of standard risk. CONCLUSIONS:HOPE is associated with improved outcomes in LT using ECD grafts and can enable the safe use of higher-risk organs with acceptable results when performed in experienced centers.

In the last decades, the world of hepatology has widely changed. Although relevant advances have be achieved (e.g. the way toward eradication of hepatitis C virus), many challenges are far to be won. Patients with liver disease continue to face noteworthy barriers to early diagnosis and effective disease management. In response to these tasks, the Italian Association for the Study of the Liver formed a multidisciplinary commission to address the unmet needs of people affected by liver diseases. We analyzed the state of the art of the following consolidated unmet needs: stigma (with particular attention to alcohol-related disease and obesity), specific criticisms of elderly, socioeconomic barriers that patients with liver disorders can face, gender gap in many aspects of liver disease and, finally, the complex issue of quality of life. For each unmet need, we proposed a key-message task and some concrete future perspectives. Preserving a holistic vision and using both multidisciplinary and interdisciplinary method, represent the only effective approach to take on the many unmet needs of patients with liver disorders.