Digestive and Liver Disease最新文献

{"title":"In vitro model of liver ischemia/reperfusion injury identifies iRhom2 as a novel disease target","authors":"R. Perriera ,&nbsp;M. Calligaris ,&nbsp;C. Carcione ,&nbsp;R. Busà ,&nbsp;V. Miceli ,&nbsp;S.D. Scilabra ,&nbsp;P.G. Conaldi ,&nbsp;M. Pinzani ,&nbsp;D. Pagano ,&nbsp;G. Zito","doi":"10.1016/j.dld.2025.08.033","DOIUrl":"10.1016/j.dld.2025.08.033","url":null,"abstract":"<div><h3>Background</h3><div>Ischemia/reperfusion injury (IRI) is a leading cause of primary non-function and both acute and chronic failure after liver transplantation. IRI creates a pro-inflammatory environment through the activation of resident Kupffer cells, ultimately compromising allograft viability and promoting rejection. iRhom2 has recently emerged as a key regulator of inflammatory and growth factor signaling, suggesting its potential involvement in IRI. However, no data are currently available on its specific role at the onset of liver injury. Here, we aimed to investigate the function of iRhom2 in liver IRI.</div></div><div><h3>Methods</h3><div>We established an in vitro IRI model using primary macrophages and iPSC-derived hepatocytes in single and co-culture systems. Cold ischemia was simulated by culturing cells in preservation medium under 2% O₂, followed by warm reperfusion for 1, 4, and 24 hours. We compared wild-type (wt) and iRhom2 knockdown (KD) macrophages and evaluated the effects of IRI by ELISA, qPCR, and ATP assays. Shotgun proteomics was performed to analyze the secretome changes in wt and iRhom2 KD cells under IRI. Hepatocyte senescence was assessed by Western blotting and β-galactosidase staining.</div></div><div><h3>Results</h3><div>We show that iRhom2 contributes to IRI progression in transplanted patients, and its downregulation in M1-like primary macrophages leads to reduced secretion of pro-inflammatory cytokines and danger-associated molecular patterns (DAMPs) implicated in IRI. Remarkably, iRhom2 silencing promotes faster macrophage recovery during reperfusion, as indicated by increased viability and reduced cytotoxicity compared to control cells. Furthermore, iRhom2 activity in macrophages drives an IRI-associated senescence phenotype in injured iPSC-derived hepatocytes by modulating the secretion of the DAMP HMGB1, which in turn activates the p21/p53 signaling pathway in target cells. Importantly, hepatocyte senescence could be prevented by anti-HMGB1 neutralizing antibodies, but not by anti-TNFα antibodies, although TNFα is another major cytokine regulated by iRhom2. These findings support the notion that iRhom2-induced HMGB1 secretion, rather than TNFα, is critical in driving hepatocyte senescence during IRI.</div></div><div><h3>Conclusion</h3><div>Overall, our data suggest that iRhom2 modulates the release of cytokines and DAMPs in response to IRI through a mechanism that is at least partly independent of the TNF pathway. Targeting iRhom2 could thus represent a promising therapeutic strategy to reduce IRI-related injury, improve graft recovery, and prevent long-term rejection mediated by hepatocyte senescence.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S330-S331"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver transplantation following HCC rupture and long-term immunotherapy: a case report","authors":"L. Di Marco ,&nbsp;M. Scoppettuolo ,&nbsp;N. De Maria ,&nbsp;A. Pivetti ,&nbsp;C. Sicuro ,&nbsp;M. Montanari ,&nbsp;V. Bernabucci ,&nbsp;A. Colecchia ,&nbsp;C. Caporali ,&nbsp;F. Casari ,&nbsp;A. Pecchi ,&nbsp;A. Spallanzani ,&nbsp;M. Dominici ,&nbsp;M. Salati ,&nbsp;B. Catellani ,&nbsp;S. Di Sandro ,&nbsp;F. Di Benedetto","doi":"10.1016/j.dld.2025.08.039","DOIUrl":"10.1016/j.dld.2025.08.039","url":null,"abstract":"<div><div>Introduction Liver transplantation (LT) provides a curative option for patients with cirrhosis and early-stage hepatocellular carcinoma (HCC). Recently, the use of immune checkpoint inhibitors (ICIs) has broadened treatment options for advanced HCC. Their role in downstaging and bridging to LT, especially in cases complicated by tumor rupture, is still under investigation. Herein, we report a case of a man with advanced HCC who underwent a successful LT after a prolonged treatment with ICIs. Case ReportA 54-year-old Caucasian male was admitted to a Spanish Hospital in June 2019 due to hypovolemic shock secondary to hemoperitoneum. A CT scan showed multifocal lesions within the liver (the majors being 8 cm in diameter at the VIIIs and 4 cm at the IIIs) with radiological features consistent with advanced HCC without biliary or vascular invasion; intraperitoneal bleeding was due to rupture of a nodule. AFP level was 219.8 ng/ml. The patient was then transferred to Our Center with a diagnosis of multifocal HCC in HCV-positive cirrhosis (see figure 1), with a preserved liver function (Child-Pugh A5). The patient underwent percutaneous intralesional injections of Pexa-Vec (3 injections) in the largest nodule and was started on Nivolumab 240 mg IV every 14 days. Both treatments were well tolerated, and no significant complications were recorded. HCV infection was treated using a direct-acting antiviral (sofosbuvir/velpatasvir), with SVR. The patient received a total of 93 ICIs infusions by May 2023. CT, MRI, and PET scans were then performed, which did not show the presence of active disease or portal vein thrombosis (see Figure 1). AFP levels were within the normal range. Considering the complete oncological response, the patient was subsequently screened for an LT, which was performed in September 2023, approximately 12 weeks after discontinuation of Nivolumab. As for July 2025, 21 months after LT, the patient is doing well; he has not experienced any episode of acute cellular rejection, and no radiological signs of HCC recurrence have been recorded. ConclusionsThis is the first case report on a successful LT performed after prolonged ICIs treatment for an advanced HCC with spontaneous intraperitoneal rupture. The positive outcome of LT challenges conventional concerns regarding peritoneal seeding and recurrence risks in ruptured HCC. Moreover, the case supports the emerging role of ICIs in managing advanced HCC, potentially extending transplant eligibility for carefully selected patients. Further research is ongoing to establish guidelines for integrating these therapies into long-term treatment LT protocols.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S333-S334"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"National Trends in Super-Urgent and Macro-Area Urgent Liver Transplantation in Italy (2019-2023): A Registry Analysis Supported by the CNT","authors":"M. Spigaroli ,&nbsp;S. Trapani ,&nbsp;N. Guglielmo ,&nbsp;S. Demma ,&nbsp;M. Colasanti ,&nbsp;C. Telesca ,&nbsp;N. Sperduti ,&nbsp;A. Pellicelli ,&nbsp;M. Merli ,&nbsp;G.M. Ettorre ,&nbsp;G. Feltrin ,&nbsp;V. Giannelli","doi":"10.1016/j.dld.2025.08.024","DOIUrl":"10.1016/j.dld.2025.08.024","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and Aims&lt;/h3&gt;&lt;div&gt;Italy manages life-threatening liver failure through two fast-track pathways: super-urgent listing (classical acute liver failure, national priority within 24–48 h) and urgent listing by macro-area (North/South) for codified indications such as MELD &gt; 30, P1 status after previous LT, or other agreed “in-deroga” cases. We analysed recent registry data to describe activity, timing and outcomes of both pathways, with a focus on the urgent-macro-area cohort.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;CNT registry data (2019-2023) were retrospectively reviewed. Indicators: listings, transplants, mean waiting time (MWT), drop-out, mortality and clinical improvement. Sub-analyses compared North vs South macro-areas and codified vs “in-deroga” urgent indications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between 2019 and 2023, the number of LT performed under the super-urgent pathway declined from 177 to 78. In 2023, the national median waiting time (MWT) for super-urgent cases was 1.8 days, with significant regional variation: 1.5 days in northern regions versus 2.1 days in the south. The overall dropout rate for super-urgent patients in 2023 was 12%. Focusing on the urgent macro-area pathway in 2023, a total of 321 patients were listed, representing a 41% increase compared to 2022, with 235 transplants performed (73%). The case-mix included 214 codified listings (91%) and 21 listings classified as “in-deroga” (9%). Among codified cases, 84% had a MELD-Na score ≥30 (n = 180), while 16% were prioritized re-transplants (Re-LT P1, n = 34).Comparison of outcome indicators between 2022 and 2023 showed a worsening in waiting times, with the MWT increasing from 5.3 to 7.1 days. However, dropout and mortality rates improved slightly: dropout decreased from 17.1% (n = 39) to 14.5% (n = 34), and mortality on the waiting list dropped from 11.0% (n = 20) to 7.0% (n = 17). Notably, the number of patients removed from the list due to clinical improvement nearly doubled, from 21 to 41.Marked disparities were observed in 2023 between northern and southern regions in urgent cases. Northern centers performed 166 transplants compared to 66 in the south, while the median waiting time was significantly longer in the south (9.2 days) than in the north (5.1 days), reinforcing the persistent regional gap in access and outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Between 2019 and 2023 Italy maintained rapid access for super-urgent candidates, yet activity declined and a modest drop-out persisted. Urgent macro-area listings grew markedly, dominated by high-MELD patients. While national performance remains good, the North–South difference in MWT (≈4 days) signals residual organisational imbalance. Recent CNT policies that shorten escalation from macro-area to national priority—and the low proportion of “in-deroga” requests—suggest progress toward more uniform, data-driven allocation. Continuous monitoring and targeted support to slower centres ","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S320"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Early HCC Recurrence After Liver Transplantation: The Predictive Value of 18F-FDG PET/CT and Microvascular invasion","authors":"L. Canova ,&nbsp;E. Alimenti ,&nbsp;M. Iavarone ,&nbsp;G. Aldinio ,&nbsp;D. Dondossolola ,&nbsp;L. Florimonte ,&nbsp;E. Franchi ,&nbsp;G. Marini ,&nbsp;C. Dibenedetto ,&nbsp;L. Caccamo ,&nbsp;M. Castellani ,&nbsp;C. Quintini ,&nbsp;P. Lampertico","doi":"10.1016/j.dld.2025.08.046","DOIUrl":"10.1016/j.dld.2025.08.046","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Liver transplantation (LT) is the most effective treatment against hepatocellular carcinoma, but recurrence remains challenging. Traditional criteria based on tumor size, nodule number and AFP levels have limited success in predicting aggressiveness. 18F-FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), a key predictor of recurrence.</div></div><div><h3>Methods</h3><div>In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. During pre-LT work-up all patients underwent 18F-FDG PET/CT and, following the LT, explant pathology was analyzed for MVI and other histological features. The primary endpoint was to identify predictors of early HCC recurrence (within 24 months after LT). Secondary endpoints included identifying predictors of high-risk histological features at explant, describing recurrence patterns, and assessing post-recurrence survival.</div></div><div><h3>Results</h3><div>The study included 143 patients (median age 59 years [IQR 54-64], 85% males, median MELD 10 [IQR 8-14], median AFP value 8.5 [IQR 4-39] ng/ml. Forty (28%) HCC resulted 18F-FDG PET/CT positive and 25 (17%) developed HCC recurrence post-LT (median post-LT follow-up 49 months [IQR 28.5-77]), with 12 (48%) experiencing early recurrence. MVI at explant was independently associated with early recurrence (HR: 7.20, 95% CI 1.82-28.45, p=0.005), while intra-hepatic 18F-FDG PET/CT positivity within six months before LT independently predicted MVI at explant (OR 3.90, 95% CI 1.30–11.71, p=0.01).</div></div><div><h3>Conclusions</h3><div>18F-FDG PET/CT is a valuable tool for pretransplant risk assessment, predicting MVI, and indirectly predicting early recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S337-S338"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four Decades of Liver Transplantation: Evolving indications, shifting epidemiology, and improved post-transplant outcomes","authors":"M.R. Attanasio,&nbsp;D. Angrisani,&nbsp;F. Picciotto,&nbsp;I. Esposito,&nbsp;G.G. Di Costanzo","doi":"10.1016/j.dld.2025.08.048","DOIUrl":"10.1016/j.dld.2025.08.048","url":null,"abstract":"<div><h3>Background</h3><div>Indications for liver transplantation (LT) changed over the past decades, driven by the introduction of direct-acting antivirals (DAAs), the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), and the expansion of criteria for hepatocellular carcinoma (HCC) listing. Advances in clinical management have led to reduce complications and improve post-transplant survival.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study at the Liver Transplant Center of Cardarelli Hospital in Naples, including 1,496 liver transplant recipients residing in Campania between 1985 and 2025, of whom 581 were transplanted at our center. Patients were stratified into three groups based on transplant period: before 2005 (Group A), 2005–2015 (Group B), and 2016–2025 (Group C). Indication for LT, post-LT neoplasms, and biliary complications were analyzed across the three cohorts.</div></div><div><h3>Results</h3><div>Most transplant recipients were male (p &gt; 0.05). The proportion of patients transplanted for HCC increased significantly over time (Group A: 15%, Group B: 50%, Group C: 46.22%; p &lt; 0.05). MASLD-related cirrhosis has become an increasingly common indication for LT, especially in the most recent decade (Group A: 2.7%; Group B: 4.7%; Group C: 15%, including 6.13% with pure MASLD;; p &lt; 0.05). Conversely, LT for HCV declined markedly (Group A: 38.3%, Group B: 45.2%, Group C: 25.4%; p &lt; 0.05). HBV and HBV/HDV cases were more prevalent in Group A (p &lt; 0.05).The incidence of de novo malignancies post-LT significantly decreased (Group A: 25.16%, Group B: 20.43%, Group C: 9.19%; p &lt; 0.05), likely due to improved immunosuppressive strategies. Although HCC recurrence rates increased (Group A: 3.1%, Group B: 6.52%, Group C: 5.18%; p &lt; 0.05), mortality from HCC recurrence progressively declined across all groups (p &lt; 0.05). Biliary complications also decreased substantially (Group A: 15.8%, Group B: 15.4%, Group C: 10.3%; p &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>The analysis of this large cohort of transplant patients highlights a significant change in indications for liver transplantation over four decades. Currently,HCC and MASLD are the primary indications for liver transplantation. Advances in clinical and immunosuppressive management have contributed to lower rates of biliary complications and de novo malignancies. Despite a rise in HCC recurrence, related mortality has declined, likely reflecting improved therapeutic options.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S338-S339"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient with alcohol-related liver disease: a multidimensional analysis","authors":"F. Mirici Cappa ,&nbsp;M. Valente ,&nbsp;C. Rossi ,&nbsp;I. Costa ,&nbsp;V. Vero ,&nbsp;A. Baldan ,&nbsp;R. Di Donato ,&nbsp;L. Golfieri ,&nbsp;P. Pianta ,&nbsp;M.C. Morelli","doi":"10.1016/j.dld.2025.08.059","DOIUrl":"10.1016/j.dld.2025.08.059","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol-related liver disease (ARLD) is liver damage caused by prolonged alcohol intake. It represents the second indication for liver transplantation in Italy, almost 20% of cases. Studies indicate that psychological-psychiatric and psychosocial variables influence the onset of the disease and the risk of relapse or alcoholic relapse post-transplant.The aim of the study is to evaluate the clinical consequences of alcohol use in liver transplant patients and the impact on the graft, analyze the rate of relapse and relapse and identify psychological-psychiatric risk and protection factors in transplant patients and transplant recipients, in terms of therapeutic adherence, number of post-transplant hospitalizations and onset of significant psychiatric events.</div></div><div><h3>Methods</h3><div>The study consists of two phases: retrospective and prospective. The retrospective phaseexamined clinical, laboratory, psychological-psychiatric and psychosocial data of patientsundergoing liver transplantation for ARLD between 2017 and 2022. The prospective,observational, spontaneous and monocentric phase involves the enrollment of patients with ARLD or etiological components of exotoxicity, afferent to the liver transplant pathway with a 5-year follow-up.</div></div><div><h3>Results</h3><div>The sample of the retrospective phase includes 208 patients, mainly men (81.3%) with a median age of 61 years. The diagnosis of liver cirrhosis, of exclusively exotoxic origin, was found in 62.5% of cases, while 24% of the sample was associated with infections by hepatotropic viruses (HCV, HBV, HIV), dysmetabolic and autoimmune causes. The median of the pre-surgery MELD is 19. 9.1% of the sample had a psychiatric diagnosis prior to transplant, 15.4% reported previous substance abuse and 9.1% reported a previous rehabilitation program. The percentage of post-transplant alcoholic relapse is 11.5% and of relapse is 5.8%.</div></div><div><h3>Conclusions</h3><div>The preliminary retrospective data push to reconsider the transplant patient and the conditions that influence the long-term prognosis and quality of life. Identifying risk profiles could provide a useful tool for the evaluation of patients in screening for transplant and outline multidisciplinary clinical paths compliant with risk factors, reducing cases of alcoholic relapse.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S344"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Other than Insulin Antidiabetic Treatment Associates with Better Status of Frailty in Patients with Cirrhosis and Type 2 Diabetes on Waiting List for Liver Transplantation","authors":"R. Vukotic ,&nbsp;C. Sommovigo ,&nbsp;G. Pratesi ,&nbsp;S. Petruccelli ,&nbsp;G. Cirillo ,&nbsp;A. Trizzino ,&nbsp;L. Petagna ,&nbsp;E. Uruci ,&nbsp;P. Carrai ,&nbsp;D. Ghinolfi","doi":"10.1016/j.dld.2025.08.061","DOIUrl":"10.1016/j.dld.2025.08.061","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Frailty is demonstrated to affect outcomes of liver transplantation (LT) and is considered a modifiable risk factor on the waiting list (WL) through adequate screening for sarcopenia and pre-habilitation. The prevalence of sarcopenia in patients with both cirrhosis and type 2 diabetes (T2D) is uncertain. At present, there are no specific guidelines for the treatment of T2D in cirrhosis. Cirrhotic patients with T2D can be prescribed with most of the currently used antidiabetic strategies, but are mostly treated with insulin. The aim of the study was to explore whether there is a distinct frailty status across patients awaiting LT with T2D according to the choice of antidiabetic strategy.</div></div><div><h3>Methods</h3><div>From January 1st to December 31st 2024, one hundred seventy-six patients entering the WL for LT were consecutively enrolled to be screened for frailty assessment as to start the pre-habilitation program prior to LT.</div></div><div><h3>Results</h3><div>Thirty-eight patients placed on WL for LT had T2D. Among them, 25 were on other than insulin antidiabetic regimen (DPP-4i, GLP-1RA, SGLT-2) and 13 were on insulin. The dynamometer measure of the isometric grip force by hand grip strength (HGS) obtained in 3 attempts resulted higher in ‘other than insulin’ antiabetics treated patients than it those insulin-treated (HGS1 kg, 27 vs 23, p=.0244, HGS2 kg, 28 vs 24, p=.0355, HGS3 kg, 28 vs 24, p=.0131). Similar trend was observed for the percentile of frailty (48 vs 61, p=.0426), Sit-to-stand test, sec (9 vs 13, p=.0571), Liver Frailty Index (3.15 vs 4, p=.0408) and pseudocholinesterase, IU/L (4490 vs 2800, p=.0157).</div></div><div><h3>Conclusions</h3><div>In patients awaiting LT who are also affected by T2D, the antidiabetic regimens other than insulin might positively impact their status of frailty. Longitudinal studies exploring dynamic changes of frailty in patients on WL with T2D could help the identification of the best treatment options for T2D in this setting and highlight the potential benefits of frailty improvement on post-LT outcomes.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S345"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of simultaneous sleeve gastrectomy and liver transplantation compared to liver transplantation alone in obese liver transplanted patients: a meta-analysis","authors":"E. Garlatti Costa ,&nbsp;E. Fumolo ,&nbsp;D. Bitetto ,&nbsp;E. Fornasiere ,&nbsp;A. Ferrarese ,&nbsp;P. Burra ,&nbsp;P. Toniutto","doi":"10.1016/j.dld.2025.08.037","DOIUrl":"10.1016/j.dld.2025.08.037","url":null,"abstract":"<div><h3>Introduction</h3><div>The morbid obesity in liver transplantation (LT) candidates is increasing. In patients failing to achieve weight loss following diet and pharmacological therapies, sleeve gastrectomy (SG) could be considered. The ideal time to perform SG remains a critical issue.</div></div><div><h3>Aim</h3><div>This meta-analysis compares, body mass index (BMI) change from baseline and mortality, 2-years after LT in obese who underwent simultaneous SG and LT compared to LT alone.Methods. A literature search of PubMed database was conducted up to June, 2025. A test of homogeneity (Cochran’s Q test) was conducted to evaluate the degree of variability across selected studies. For BMI change, meta-analyses were conducted using Cohen’s d as the effect size. All analyses were performed using a significance level of α =0,05. Statistical analyses were carried out using IBM SPSS Statistics version 30.</div></div><div><h3>Results</h3><div>Among the 180 articles selected, 3 were considered eligible. Overall, 348 patients were enrolled; 99 and 249 underwent LT+SG and LT alone respectively. A significantly higher BMI decrease from baseline in LT+SG compared to LT alone group 2-years after LT (p &lt;0,001) was reported in the 2/3 studies eligible (Fig. 1). No significant differences in mortality were recorded between groups (p =0,478) (Fig. 2).</div></div><div><h3>Conclusions</h3><div>Simultaneous SG and LT compared to LT alone, resulted in a greater BMI reduction, without increasing the risk of mortality 2 years after LT. Further studies are needed to confirm these results and to assess the benefit of BMI decrease in preventing/treating the recurrence of metabolic associated steatotic liver disease (MASLD).</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S332-S333"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LIRICA and LITALHICA: Redefining Liver Transplantation for Cholangiocarcinoma Through a Multidisciplinary Tumor Board Approach","authors":"E. Gringeri ,&nbsp;A. Furlanetto ,&nbsp;D. Pinelli ,&nbsp;S. Gruttadauria ,&nbsp;A. Lauterio ,&nbsp;F. Di Benedetto ,&nbsp;R. Romagnoli ,&nbsp;D. Ghinolfi ,&nbsp;A. Carraro ,&nbsp;M. Vivarelli ,&nbsp;J. Lanari ,&nbsp;E. Nieddu ,&nbsp;E. Rosso ,&nbsp;S. Lazzari ,&nbsp;C. De Nardi ,&nbsp;I. Billato ,&nbsp;S. Trapani ,&nbsp;M. Cardillo ,&nbsp;G. Feltrin ,&nbsp;L. De Carlis ,&nbsp;U. Cillo","doi":"10.1016/j.dld.2025.08.041","DOIUrl":"10.1016/j.dld.2025.08.041","url":null,"abstract":"<div><h3>Background</h3><div>Liver transplantation (LT) for perihilar cholangiocarcinoma (pCCA) provides outstanding outcomes within the Mayo Clinic protocol (MP). However, an Italian survey revealed that, since 2015, 39% of pCCA patients undergoing LT deviated from the MP due to recurrent cholangitis, untreatable hyperbilirubinemia, or logistical obstacles. Major concerns include diagnostic difficulties, the effect of radiotherapy, and the need to change chemotherapy from the standard of care (SOC). Intrahepatic cholangiocarcinoma (iCCA) has traditionally been a contraindication for LT, but recent studies have explored its potential as a novel transplant oncology indication.</div></div><div><h3>Methods</h3><div>We developed two similar study protocols that propose LT for unresectable iCCA (LIRICA) and pCCA (LITALHICA) after SOC neoadjuvant chemotherapy, serving as a test of time and to asses tumor biology. A multidisciplinary board (comprising hepatobiliary surgeons, transplant surgeons, oncologists, and radiologists) assesses tumor unresectability and confirms adherence to inclusion criteria, providing endorsements for approval by the Italian National Transplantation Center (CNT). Eligible patients undergo six months of SOC chemotherapy and are then restaged by CT, PET-MRI, and diagnostic laparoscopy. Those with stable disease or partial response proceed to transplantation, while patients with disease progression receive second-line chemotherapy.</div></div><div><h3>Results</h3><div>Since protocol approval (January 2024), 72 patients from 12 Italian centers have been evaluated (26 LITALHICA, 46 LIRICA). Of these, 10 were rejected based on exclusion criteria, and 32 were deemed eligible but could not be enrolled in the prospective protocols due to prior chemotherapy initiation. The first per-protocol LITALHICA case was aborted due to peritoneal carcinomatosis at exploratory laparotomy. The first LIRICA patient was successfully transplanted in August 2024 and is alive and recurrence-free after nearly one year. A total of 14 patients received LT while five patients are awaiting LT.</div></div><div><h3>Conclusions</h3><div>Expanding the indications for LT requires robust scientific evidence from prospective trials. A multidisciplinary expert board provides the most effective framework for ensuring rigorous, case-by-case evaluation and strict adherence to criteria, efficiently balancing the principles of resectability and radicality.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S335"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution during the last 20 years, before and after the introduction of DAA, of the characteristics and comorbidities of patients on the waiting list for liver transplantation in a single center","authors":"E. Coltorti ,&nbsp;S. Parisse ,&nbsp;F. Ferri ,&nbsp;F. Melandro ,&nbsp;Q. Lai ,&nbsp;G. Mennini ,&nbsp;M. Rossi ,&nbsp;S. Ginanni Corradini","doi":"10.1016/j.dld.2025.08.045","DOIUrl":"10.1016/j.dld.2025.08.045","url":null,"abstract":"<div><h3>Background</h3><div>The rising prevalence of metabolic syndrome and the decline in HCV rates due to Direct-Acting Antivirals (DAAs) have reshaped the liver transplantation (LT) landscape, leading to more complex evaluations and increased resource needs. The Charlson Comorbidity Index (CCI) has been proposed as a predictor of post-LT outcomes.</div></div><div><h3>Aims</h3><div>to evaluate the impact of epidemiological changes on WL composition, comparing etiology and comorbidities in the pre- and post-DAA eras.</div></div><div><h3>Methods</h3><div>We analyzed all consecutive patients listed for LT from 2005 to 2024, dividing them into pre-DAA (2005–2014) and post-DAA (2015–2024) eras. CCI was calculated for patients with available data on nine comorbidities: diabetes, stroke, coronary artery disease, chronic kidney disease, COPD, peripheral vascular disease, connective tissue disease, congestive heart failure, and prior extrahepatic malignancies. CCI considered categories were 0, 1–2, and &gt;3.</div></div><div><h3>Results</h3><div>We analyzed 648 patients: 55% (n=358) pre-DAA and 45% (n=290) post-DAA. Post-DAA patients were older and had higher median MELDNa scores [54.4 (47.9–60.3) vs 56.9 (49.1–63), p=0.003] and [16 (12–21) vs 17 (13–24), p=0.033]. HCC prevalence was similar. Metabolic dysfunction–associated steatotic liver disease (MASLD) was more common post-DAA (41% vs 24%, p&lt;0.0001), while HCV was less frequent (24% vs 35%, p=0.001). Other etiologies showed no significant differences. CCI was available for 313 pre-DAA and 290 post-DAA patients. Higher CCI scores were significantly associated with MASLD (p&lt;0.0001), older age (p&lt;0.0001), and were more common post-DAA (CCI 0 in 47% vs 52%, CCI 1–2 in 40% vs 32%, and CCI &gt;3 in 18% vs 11% p=0.001).</div></div><div><h3>Conclusion</h3><div>WL composition changed substantially over 20 years, with nearly doubled MASLD prevalence and greater disease severity. Increased extrahepatic comorbidities are probably due to older age and higher metabolic syndrome rates. These trends imply greater demands for pre-transplant assessment and potentially worse post-transplant outcomes.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S337"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}