This review explores the evolving role of endoscopic ultrasound (EUS) in the diagnosis and management of liver diseases, with a particular focus on chronic liver disease, focal hepatic lesions, portal hypertension, and post-transplant anatomy. A comprehensive literature review of PubMed, MEDLINE, and Embase studies up to August 2025 was conducted to identify the latest evidence on EUS-guided procedures, comparing them with traditional techniques. In diagnostics, EUS-guided liver biopsy provides real-time visualisation and precise tissue sampling, achieving longer specimen lengths and better patient outcomes compared to traditional percutaneous and transjugular approaches. For portal hypertension assessment, EUS-guided portal pressure gradient measurement is a promising alternative to conventional methods, with validation studies demonstrating strong correlation with hepatic venous pressure gradient measurements. In therapeutic applications, EUS facilitates precise interventions including gastric variceal treatment through combined coil and glue injection, management of visceral arterial pseudoaneurysms, selective portal vein embolisation, and targeted tumour ablation. While some applications remain in developmental stages, studies support the safety and efficacy of EUS in improving diagnostic accuracy and expanding therapeutic options for liver diseases. Ongoing technological advances in needle design, imaging capabilities, and artificial intelligence integration are expected to further enhance the utility of EUS in hepatology.

Supplementary Method S1. Dendritic cell manufacture.

BACKGROUND:Digital single-operator cholangioscopy (dSOC) has improved the diagnostic accuracy of indeterminate biliary duct strictures (IBDS) through targeted intraductal biopsy sampling. However, the optimal biopsy technique remains uncertain. METHODS:This international, multicenter, prospective interventional study (November 2020-August 2022) included patients with IBDS undergoing dSOC. Stricture sampling involved obtaining at least four single biopsies and at least one bite-on-bite biopsy (BBB) in all patients. Definitive diagnosis was established by pathology outcomes and 1-year clinical follow-up. The primary outcome was the accuracy of both biopsy techniques. RESULTS:89 patients were included, with 76 hilar strictures and 13 distal strictures. Technical success for obtaining adequate tissue samples was 82/89 (92.1 %) for single biopsies and 78/89 (87.6 %) for BBB. Malignancy was confirmed in 31/82 (37.8 %) and 29/78 (37.2 %) cases in single biopsies and BBB, respectively. Among 76 patients in whom both techniques were successful, pathology results were discordant in three cases (3.9 %), primarily due to understaging by BBB. Among 82 patients with complete follow-up, malignancy was confirmed in 51 (62.2 %). Sensitivity, specificity, and accuracy for malignancy or high grade dysplasia were 66.0 %, 100 %, and 78.8 % for single biopsies, and 63.8 %, 100 %, and 77.6 % for BBB, respectively. Sensitivity and accuracy were significantly decreased after stent placement or intraductal tissue acquisition during prior ERCP. The number of BBBs did not impact sensitivity or accuracy. CONCLUSIONS:BBB did not outperform at least four single biopsies for IBDS. Prior manipulation of IBDS, through stent placement or prior tissue acquisition, was associated with a decreased diagnostic yield.

PURPOSE:A previous study by our group using dendritic cells (DC) pulsed ex vivo with the lysate of the HepG2 cell line showed evidence of antigen-specific T-cell responses in some patients with advanced hepatocellular carcinoma. The ImmunoTACE trial evaluated the preliminary activity of this vaccine in combination with transarterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma. PATIENTS AND METHODS:A randomized phase II trial was conducted in three tertiary referral centers in the United Kingdom. Eligible patients were randomly assigned in a 1:1 ratio to TACE + preconditioning cyclophosphamide or to TACE + preconditioning cyclophosphamide + DC infusions. The primary endpoint was progression-free survival time using RECIST v1.1 criteria. Additional endpoints included safety and immune responses. RESULTS:Between March 2016 and October 2019, 55 patients were randomized, of whom 48 were evaluable (24 in each group). The median progression-free survival time using RECIST criteria was 18.6 months in patients treated with chemoembolization + preconditioning cyclophosphamide + DC infusions compared with 10.4 months in those treated with chemoembolization + preconditioning cyclophosphamide alone (HR = 0.43; upper value of one-sided 80% confidence interval, 0.57; P = 0.016). The addition of DC infusions did not significantly increase the incidence or severity of adverse events. An enhanced antigen (α-fetoprotein)-specific immune response was observed in patients treated with DC vaccination. CONCLUSIONS:The addition of DC infusions to TACE and preconditioning cyclophosphamide has shown promising preliminary activity and merits further investigation in a larger randomized trial.

Aims Indeterminate biliary duct strictures (IBDS) are a difficult diagnostic challenge. Digital single operator cholangioscopy (d-SOC) has improved diagnostic yield by the ability to obtain targeted intra-ductal biopsies by direct mucosal visualization. However, the optimal biopsy technique remains unclear. The aim of this study was to compare the diagnostic yield of d-SOC guided single standard biopsies to those obtained via bite-on-bite-biopsy (BBB) technique in patients with IBDS.

Background and study aims Pancreatic cysts are common incidental findings, with an estimated prevalence of 13% to 15% in imaging done for other reasons. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS). The primary aim was to assess the performance of NGS in identifying mucinous cyst. The secondary aims were to assess DNA yield between the cyst fluid and cyst wall tissue, complication rate and performance of conventional investigations.Patients and methods Twenty-four patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a polymerase chain reaction assay targeting several hotspots within 50 genes, including GNAS , KRAS and VHL .Results The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the nine of 24 available matched cyst fluid samples. The sensitivity, specificity, and diagnostic accuracy of NGS for diagnosing mucinous cyst were 93%, 50% and 84%; for standard of care, they were -66.6%, 50% and 63.1%; and for standard of care with NGS, they were 100%, 50%, and 89.4% respectively. Cyst wall biopsy was able to diagnose 19 of 24 cysts (4 high risk, 7 intraductal papillary mucinous neoplasms, 4 cysts of mucinous origin, and 4 benign).Conclusions NGS data correlate well with histology and may aid in diagnosis and risk stratification of pancreatic cysts. Cyst wall biopsy performs well in diagnosing cysts but was inadequate in five of 24 patients.

Introduction While non-invasive tests are increasingly used to risk stratify fibrosis, liver biopsy (LB) remains the gold standard for diagnosis and staging. Percutaneous LB (P-LB) and transjugular LB (TJLB) are well-established methods for tissue acquisition, while endoscopic ultrasound-guided liver biopsy (EUS-LB) is a novel approach. Our primary aim was to compare diagnostic adequacy of EUS-LB against P-LB and TJLB. Secondary aims were to assess adequacy of fibrosis staging, length of stay post-procedure and 30-day complication rates between different modalities. Methods Data was collected prospectively from patients undergoing non-lesional P-LB, TJLB or EUS-LB in a single tertiary hospital from September 2022 to February 2023. The study was approved by the Trust review board. P-LB used 16G Biopince® needle performed by hepatologists or interventional radiologists, TJLB used 18G Argon® needle by interventional radiologists and EUS-LB used a 19G Acquire® FNB needle by endohepatologists. Demographics, biopsy indication, cumulative specimen length, number of complete portal tracts (CPT), length of stay (LoS), 30-day complications and diagnostic yield were recorded. Diagnostic adequacy was assessed by comparing cumulative specimen length and CPTs between techniques, using BSG guideline standards (>11 CPTs; specimen length ≥ 20mm). Histopathology assessment blinded to technique gave a fibrosis score and clinical diagnosis for each sample. Results 121 patients (51% male) had a liver biopsy. Mean age was 55.2 years, and was similar across groups (p= 0.82). Fifty nine (49%) biopsies were P-LB, 10 (8.2%) were TJLB and 52 (43%) were EUS-LB. Fifty eight samples reported number of CPTs and 100 reported total specimen length. Median cumulative length was 27mm, 26mm and 41.5mm for P-LB, TJLB and EUS-LB respectively (p<0.01). Median number of CPTs was comparable between techniques: 19 for P-LB, 14.5 for TJLB and 22.5 for EUS-LB, (p=0.29). Samples were sufficient for histological diagnosis in 97% in P-LB, 100% in TJLB and 97% of EUS-LB cases. Complications occurred in 2 following P-LB (significant bleed; pain) and 1 following EUS-LB (duodenal wall perforation); all resolved with medical management. Patients undergoing EUS-LB had a significantly lower median LoS (3.22 hours), than those undergoing P-LB (8.01 hours) and TJLB (4.55 hours);p <0.001. Adequacy for fibrosis staging was 96% in P-LB samples, 90% in TJLB and 95% of EUS-LB (p=ns). Discussion The diagnostic utility and adequacy of fibrosis staging using EUS-LB compared favourably with other established techniques. Length of post-procedural stay was significantly lower for patients undergoing EUS-LB, which may release cost-savings in Daycase services, but presents challenges in training and service delivery compared to traditional LB pathways. Future comprehensive liver assessment may include single session EUS elastography, variceal screening, biopsy and portal pressure assessment.

ABSTRACTChylous ascites is a rare condition found in 1 in 20 000 patients admitted to hospital with abdominal distention. It is caused by a limited number of pathologies but can, in rare situations, be idiopathic. Its management is difficult and usually involves correcting the primary pathology, making idiopathic chylous ascites particularly difficult to manage. We present a case of idiopathic chylous ascites extensively investigated over a period of several years. An incidental finding of B cell lymphoma was initially suspected to have been the primary cause of the ascites; however, after successful treatment of this condition, the patient’s ascites did not resolve. Diagnostic difficulties and management are discussed and an overview of the diagnostic process is outlined through this case.

Background and Aims: EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. Methods: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. Results: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to <= 50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). Conclusions: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study investigated these discrepancies and considered whether a tissue water content correction, as assessed by MRI relaxometry, could provide better agreement. 110 patients were scanned in a 1.5 T Philips scanner and biopsies were obtained. Multiple echo MRS (30 × 30 × 30 mm volume) was used to determine Proton Density Fat Fraction (PDFF). Biopsies were assessed by visual assessment for fibrosis and steatosis grading. Digital image analysis (DIA) was also used to quantify fat fraction within tissue samples. T1 relaxation times were then used to estimate tissue water content to correct PDFF for confounding factors. PDFF values across the four visually assessed steatosis grades were significantly less in the higher fibrosis group (F3–F4) compared to the lower fibrosis group (F0–F2). The slope of the linear regression of PDFF vs DIA fat fraction was 1 in the low fibrosis group and 0.77 in the high fibrosis group. Correcting for water content based on T1 increased the gradient but it did not reach unity. In fibrotic livers, PDFF underestimated fat fraction compared to DIA methods. Values were improved by applying a water content correction, but fat fractions were still underestimated.

“Band and leave” strategy has been described for the resection of submucosal tumors of the digestive tract to reduce the complications related to deep submucosal resection such as bleeding and perforation. We present the case of a patient with multiple comorbidities, chronic liver disease, and portal hypertension diagnosed to have T1 adenocarcinoma in Barrett's esophagus overlying a column of varix. This was successfully treated by band ligation and allowing the neoplastic mucosa to slough. We propose this technique as an alternative therapeutic option for the management of early Barrett's neoplasia in such high-risk patients with portal hypertension.

Introduction: Alcohol is the leading cause of cirrhosis in Western populations. The early identification of high-risk drinkers followed by intervention is an effective way to reduce harm. We aim to assess the feasibility of integrating transient elastography (TE) into community alcohol services, and to determine its impact on modifying drinking behaviours. Method: A prospective cohort study was conducted at a community alcohol clinic in Nottingham, UK (April 2012 to March 2014). Patients (>18 years) with a primary alcohol problem were recruited. Those known to liver services or those known to have chronic liver disease were excluded. Significant liver fibrosis was defined by a liver stiffness of >8 kilopascal (kPa). Follow-up was for a minimum of six months. Data were descriptively analysed for significant differences between patients with a normal liver stiffness versus raised liver stiffness. Results: 156 patients were invited; n = 87 attended and n = 86 underwent successful TE. The majority were male (n = 53, 70.0%), and the mean age was 46.3 years (SD ± 9.8). Median liver stiffness was 6.9 kPa (range 3.1–75.0kPa). Clinically significant liver fibrosis was identified in n = 33 (38.4%), of which n = 6 were in the cirrhotic range (≥15 kPa). The baseline median self-reported alcohol intake for normal stiffness was 126 units per week (range 24–378) and in raised stiffness was 149.0 units per week (range 39.0–420.0); this difference was nonsignificant (p = 0.338). The median reduction in self-reported alcohol intake in the whole cohort was 65.0 units per week (range 27.0–88.0, p < 0.001); in the normal liver stiffness group it was 25.0 units per week (range 18.0–75.0, p = 0.154), and in the raised liver stiffness group it was 78.5 units per week (range 36.0–126.0, p < 0.001). Conclusion: The study demonstrated that transient elastography is a feasible tool to stratify clinically significant liver disease in community alcohol services. It can stimulate a change in high-risk drinking behaviour and a normal liver stiffness result does not provide false reassurance to participants.

Introduction Alcohol is the leading cause of cirrhosis in western populations. Early identification of high-risk drinkers followed by intervention is an effective way to reduce harm. We aim to assess the feasibility of integrating transient elastography (TE) into community alcohol services and to determine its impact on modifying drinking behaviours. Method A prospective cohort study was conducted at a community alcohol clinic in Nottingham (April-2012 to March-2014). Patients (>18years) with a primary alcohol problem were recruited. Those known to liver services or to have chronic liver disease were excluded. Significant liver fibrosis was defined by a liver stiffness measure (LSM) of >8 kilopascals (kPa). Follow-up was for a minimum of six months. Data were descriptively analysed for significant differences between patients with a normal LSM versus raised LSM. Results 156 patients were invited; n=87 attended and n=86 underwent successful TE. The majority were male (n=53, 70.0%) and the mean age was 46.3 years (SD +/-9.8). Median liver stiffness was 6.9kPa. Clinically significant liver fibrosis was identified in n=33 (38.4%), of which n=6 were in cirrhotic range (≥15 kPa). Baseline median self-reported alcohol intake for normal stiffness was 126 units per week and in raised stiffness was 149.0 units per week the difference was non-significant (p=0.338). Median reduction in self-report alcohol intake in whole cohort was 65.0 units per week (p=<0.001), in normal liver stiffness group was 25.0 units per week (p=0.154), and in raised liver stiffness group was 78.5 units per week (p<0.001). Conclusion The study demonstrated that transient elastography is a feasible tool to stratify clinically significant liver disease in community alcohol services. It can stimulate a change in high-risk drinking behaviour and a normal liver stiffness result does not provide false reassurance to participants.

Endoscopic ultrasound guided choledochoduodenostomy (EUS-CDD) with electrocautery enhanced lumen apposing metal stents (EC-LAMS) has recently emerged as a viable option in the management of patients with malignant distal biliary obstruction (MDBO). We conducted a multi-centre collaboration from the UK and Ireland with an aim to analyse the pooled efficacy, safety and long term outcomes of EUS-CDD for treatment of MDBO.

Introduction Endoscopic ultrasound guided choledochoduodenostomy (EUS-CDD) with electrocautery enhanced lumen apposing metal stents (EC-LAMS) has emerged as a viable option in the management of patients with malignant distal biliary obstruction (MDBO). We conducted a multi-centre collaboration from the UK and Ireland with an aim to analyse the pooled efficacy, safety and long term outcomes of EUS-CDD for treatment of MDBO. Methods Consecutive patients with MDBO who underwent EUS-CDD with EC-LAMS at 8 tertiary hepatopancreatobiliary institutions between September 2016 and September 2020 were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and follow-up data. Results 112 patients (59 male) were identified. The mean age was 72 years old (range 46 - 94 years old). Pancreatic adenocarcinoma was the commonest underlying malignancy in 63.4% (n=71). The indications for EUS-CDD were: an inaccessible papilla (n=49), tumour infiltration of papilla (n=29) and unsuccessful biliary cannulation/stricture impassable with guidewire (n=34). Technical success was achieved in 91.1% (n=102) of patients. Additional stenting with plastic pigtails through the EC-LAMS was performed in 26 patients at the discretion of the endoscopist to augment biliary drainage. Data for clinical success (reduction of serum bilirubin to ≤50% of original value at day 7) was available for 90 patients and was achieved in 94.4% of these (n=84). The adverse event rate was 16.9% (n=19) and further details are summarised in the table. The biliary re-intervention rate was 8.1% (n=8) in 99 patients with successful EUS-CDD (3 lost to follow-up), over a median follow-up of 70 days (range 3 - 761 days). Eight patients underwent attempted surgical resection of their primary tumour and in those who did, resection and formation of hepaticojejunostomy was successful. Conclusion We present the first collaborative data from the UK and Ireland demonstrating EUS-CDD in MDBO to be efficacious with a reasonable safety profile.

INTRODUCTION Increasing rates of liver transplantation and improved outcomes have led to greater numbers of transplant recipients followed up in non-transplant centres. Our aim was to document long-term clinical outcomes of liver transplant recipients managed in this 'hub-and-spoke' healthcare model. METHODS A retrospective analysis of all adult patients who underwent liver transplantation between 1987 and 2016, with post-transplant follow-up in two non-transplant centres in the UK (Nottingham) and Canada (Ottawa), was performed. RESULTS The 1-, 5-, 10- and 20-year patient survival rates were 98%, 95%, 87% and 62%, and 100%, 96%, 88% and 62% in the Nottingham and Ottawa groups, respectively (p=0.87). There were no significant differences between the two centres in 1-, 5-, 10- and 20-year cumulative incidence of death-censored graft-survival (p=0.10), end-stage renal disease (p=0.29) or de novo cancer (p=0.22). Nottingham had a lower incidence of major cardiovascular events (p=0.008). CONCLUSION Adopting a new model of healthcare provides a means of delivering post-transplant patient care close to home without compromising patient survival and long-term clinical outcomes.