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Metal nanomaterials, such as silver and copper, are often incorporated into commercial textiles to take advantage of their antibacterial and antiviral properties. In this study eight different methods were employed to synthesize silver, copper, and silver/copper functionalized cotton batting textiles. Using silver and copper nitrate as precursors, different reagents were used to initiate/catalyze the deposition of metal, including: (1) no additive, (2) sodium bicarbonate, (3) green tea, (4) sodium hydroxide, (5) ammonia, (6,7) sodium hydroxide/ammonia at a 1:2 and 1:4 ratio, and (8) sodium borohydride. The use of sodium bicarbonate as a reagent to reduce silver onto cotton has not been used previously in literature and was compared to established methods. All synthesis methods were performed at 80°C for one hour following textile addition to the solutions. The products were characterized by X-ray fluorescence (XRF) analysis for quantitative determination of the metal content and X-ray absorption near edge structure (XANES) analysis for silver and copper speciation on the textile. Scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) and size distribution inductively coupled plasma mass spectrometry (ICP-MS) were used to further characterize the products of the sodium bicarbonate, sodium hydroxide, and sodium borohydride synthesis methods following ashing of the textile. For the silver treatment methods (1 mM Ag+), sodium bicarbonate and sodium hydroxide resulted in the highest amounts of silver on the textile (8900 mg Ag/kg textile and 7600 mg Ag/kg textile) and for copper treatment (1 mM Cu+) the sodium hydroxide and sodium hydroxide/ammonium hydroxide resulted in the highest amounts of copper on the textile (3800 mg Ag/kg textile and 2500 mg Ag/kg textile). Formation of copper oxide was dependent on the pH of the solution, with 4 mM ammonia and other high pH solutions resulting in majority of the copper on the textile existing as copper oxide, with smaller amounts of ionic-bound copper.

As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment. Well-recognised risks include those of general anaesthesia, bleeding, infections, impaired wound healing, acute kidney injury and cardiovascular compromise. Intra-abdominal or cardiothoracic surgery are particularly high-risk interventions. Clinical assessment supplemented by blood tests, imaging, liver stiffness measurement, endoscopy and assessment of portal pressure (derived from the hepatic venous pressure gradient) can facilitate risk stratification. Traditional prognostic scoring systems including the Child-Turcotte-Pugh and Model for End-stage Liver Disease are helpful but may overestimate surgical risk. Specific prognostic scores like Mayo Risk Score, VOCAL-Penn and ADOPT-LC can add precision to risk assessment. Measures to mitigate risk include careful management of varices, nutritional optimisation and where possible addressing any ongoing aetiological drivers such as alcohol consumption. The role of portal decompression such as transjugular intrahepatic portosystemic shunting can be considered in selected high-risk patients, but further prospective study of this approach is required. It is of paramount importance that patients are discussed in a multidisciplinary forum, and that patients are carefully counselled about potential risks and benefits.

Splenomegaly is a hallmark of myelofibrosis, a debilitating haematological malignancy for which the only curative option is allogeneic haematopoietic cell transplantation (HCT). Considerable splenic enlargement might be associated with a higher risk of delayed engraftment and graft failure, increased non-relapse mortality, and worse overall survival after HCT as compared with patients without significantly enlarged splenomegaly. Currently, there are no standardised guidelines to assist transplantation physicians in deciding optimal management of splenomegaly before HCT. Therefore, the aim of this Position Paper is to offer a shared position statement on this issue. An international group of haematologists, transplantation physicians, gastroenterologists, surgeons, radiotherapists, and radiologists with experience in the treatment of myelofibrosis contributed to this Position Paper. The key issues addressed by this group included the assessment, prevalence, and clinical significance of splenomegaly, and the need for a therapeutic intervention before HCT for the control of splenomegaly. Specific scenarios, including splanchnic vein thrombosis and COVID-19, are also discussed. All patients with myelofibrosis must have their spleen size assessed before allogeneic HCT. Myelofibrosis patients with splenomegaly measuring 5 cm and larger, particularly when exceeding 15 cm below the left costal margin, or with splenomegaly-related symptoms, could benefit from treatment with the aim of reducing the spleen size before HCT. In the absence of, or loss of, response, patients with increasing spleen size should be evaluated for second-line options, depending on availability, patient fitness, and centre experience. Splanchnic vein thrombosis is not an absolute contraindication for HCT, but a multidisciplinary approach is warranted. Finally, prevention and treatment of COVID-19 should adhere to standard recommendations for immunocompromised patients.

Pre-emptive transjugular intrahepatic portosystemic shunt (pTIPSS) should be considered within 72 hours following acute oesophageal variceal bleeding. However, recent studies highlight the difficulty in providing pTIPSS within this narrow timeframe. Delaying pTIPSS beyond 72 hours has not been studied.To determine if the time taken to perform pTIPSS alters patient outcome.Patients referred to 4 UK tertiary centres for pTIPSS between 01 January 2010 and 31 December 2018 were included. Time from endoscopy to pTIPSS was recorded and pre-defined clinically relevant outcomes were observed relative to two groups: early pTIPSS (72 h) and late pTIPSS (72 h-28 days). The primary outcome was transplant-free survival at 1-year. Follow-up was until 31 December 2020.A total of 83 patients received early pTIPSS and 88 received late pTIPSS. Baseline characteristics were similar with no requirement for propensity score-matched analysis. There was no difference between early and late pTIPSS groups for patient outcomes; 1-year transplant-free survival rate (69.9% vs 71.6%, p = 0.73, HR 0.91, 95% CI 0.52-1.58), long-term survival (p = 0.52, HR 1.132, 95% CI 0.77-1.65), variceal rebleeding (4.82% vs 11.36%, p = 0.09, HR 0.411, 95% CI 0.14-1.17), hepatic encephalopathy (43.93% vs 34.61%, p = 0.26) and new or worsening ascites (16.6% vs 13.46%, p = 0.79). Death due to liver failure was significantly more prevalent in those undergoing early pTIPSS compared to late pTIPSS (44% vs 16%, p = 0.046, HR 2.79, 95%CI 1.02-8.32).Placement of pTIPSS within 72 hours offered similar short- and long-term survival benefits compared to pTIPSS placed between 72 hours and 28 days. Early pTIPSS may be associated with an increased risk of liver failure-related mortality. Further large, randomised studies are required to evaluate these findings.

Introduction The impact of sarcopenia in patients undergoing transjugular intrahepatic portosystemic shunt (TIPSS) insertion for refractory ascites is unknown. Methods All adult patients who underwent TIPSS insertion for refractory ascites between 2010 and 2018 were included. Skeletal muscle index at L3 was used to determine sarcopenia status. Results One hundred seven patients were followed for 14.2 months. Sarcopenia was present in 57% of patients. No patient had history of pre-TIPSS hepatic encephalopathy (HE). De novo HE occurred in 30% of patients. On multivariate analysis, only platelet count and L3-SMI predicted de novo HE. On multivariate analysis, age and model for end-stage liver disease with sodium predicted mortality, whereas L3-SMI and sarcopenia did not. In patients with repeat imaging, L3-SMI improved significantly post-TIPSS compared with baseline. Discussion Sarcopenia should not be considered as a contraindication to TIPSS insertion in refractory ascites because it is not associated with de novo HE or increased mortality.

BACKGROUND Tacrolimus minimization is usually restricted to patients with pretransplant renal impairment, and this strategy could result into worse renal outcomes after liver transplantation (LT). METHODS A consecutive cohort of 455 LT patients receiving tacrolimus-based immunosuppression was studied (2008-2013). Cumulative exposure to tacrolimus was calculated as the area under curve of trough concentrations (AUCtc). Patients were stratified as tacrolimus minimization, conventional, or high exposure, according to the thresholds based in the COMMIT consensus. Estimated glomerular filtration rates (eGFR) were assessed by the Modification of Diet in Renal Disease formula (MDRD-4) up to 5 years after LT. RESULTS Seventy patients (15.4%) had pretransplant eGFR < 60 mL/min, which was associated with increased mortality rates, particularly within the first 5 years post-LT (31.4% versus 17.5%; Breslow P = 0.010). After LT, there was an abrupt eGFR decline within the first 3 months (median 18.6 mL/min; P < 0.001), further decreasing up to 12 months (additional 3 mL/min), without any improvement thereafter. According to AUCtc, 33.7% of patients received tacrolimus minimization, 44.8% conventional exposure, and 21.5% high exposure. Conventional/high exposure to tacrolimus resulted in a more pronounced eGFR decline within the first 3 months when compared with minimization (23.3 mL/min versus 9.5 mL/min; P < 0.001). This gap was even higher in patients with initially preserved renal function. Tacrolimus AUCtc was an independent predictor of eGFR decline within the first 3 months after controlling for potential confounders. CONCLUSIONS AUCtc is a surrogate of cumulative exposure to tacrolimus and may be helpful for routine dose adjustments. Tacrolimus minimization should be universally attempted after LT to preserve renal function.

Per- and polyfluoroalkyl substances (PFAS) are a challenging class of environmental pollutants due to a lack of available destructive remediation technologies. Understanding the fundamental mechanisms for degradation of PFAS is key for the development of field scalable and in-situ destructive based remediation technologies. This study aimed to elucidate and refine the current understanding of PFAS degradation mechanisms in water through a series of controlled gamma irradiation studies. Gamma irradiation of PFAS was performed using a cobalt-60 source in a batch irradiation up to 80 kGy at the Australian Nuclear Science and Technology Organisation. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6:2 fluorotelomer sulfonate (6:2 FTS), and a suite of thirteen different PFAS (including C4-C12 PFCAs, C4, C6, C8 PFSAs, and FOSA) were irradiated to investigate degradation, influence of pH, chain length, and transformation. High resolution mass spectrometry was used to identify more than 80 fluorinated transformation products throughout the degradation experiments. These included the -F/+H, -F/+OH, -F/CH

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large‐volume transfusion. This retrospective, single‐center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16‐29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.

Introduction Transjugular intrahepatic portosystemic stent-shunt (TIPSS) insertion is well established as an effective treatment for the management of bleeding in patients with decompensated cirrhosis. Current evidence suggests that early TIPSS (within 72 hours of a variceal bleed) using the GORE® VIATORR® stent effectively reduces portal pressure and improves prognosis in comparison to endoscopic band ligation (EBL) and medical management. We conducted a meta-analysis of trials comparing early TIPSS with EBL in cirrhotic patients with acute variceal bleeding. Methods Systematic literature searches were conducted in MEDLINE, PubMed, EMBASE and Cochrane. Eligible studies were published between May 1999 and May 2020. The outcomes of interest were survival, re-bleeding and rate of hepatic encephalopathy. Risk Ratio (RR) estimates with 95% confidence interval (CI) were calculated using a random effects model and trials were evaluated using the Cochrane tool for the assessment of the risk of bias. Results 8,123 studies were identified by the search and three prospective controlled trials including 152 patients were included in the meta-analysis. Meta-analyses demonstrated that GORE® VIATORR® consistently and significantly reduced incidence of bleeding (RR = 0.20, 95% CI = 0.09–0.42, p = Conclusion TIPSS is more effective in preventing variceal re-bleeding than EBL and medical management, without an increase adverse events. While this was not associated with a statistically significant improvement in survival, it is likely that these findings were underpowered. High quality, adequately powered and multi-centre randomized trials evaluating clinical and quality of life outcomes are required to verify these results and inform robust economic evaluations of TIPSS in the management of variceal bleeding in patients with cirrhosis.

Introduction Variceal bleeding and refractory ascites are common clinical manifestations of liver cirrhosis. Transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedures can increase survival and improve quality of life in some cirrhotic patient populations. TIPSS is clinically effective: versus endoscopic band ligation (EBL) in second line treatment of variceal bleeding; and versus large volume paracentesis (LVP) in refractory ascites. However, there is a sparsity of UK based economic evidence determining the cost-effectiveness of TIPSS for these two indications. This study aimed to establish the cost-effectiveness of (i) TIPSS versus EBL in second line treatment of variceal bleeding, and (ii) TIPSS versus LVP in the management of refractory ascites. Methods A cost-utility analysis was conducted from a UK health perspective including NHS costs and quality adjusted life years (QALYs). A Markov model was constructed which included health states for survival either with or without complications of liver cirrhosis including variceal bleeding, ascites and hepatic encephalopathy. The model was conducted across a 2-year time horizon and applied costs and dis-utilities per complication for each monthly cycle. Uncertainty was analysed in one-way deterministic and probabilistic sensitivity analyses. Results TIPSS with the GORE® VIATORR® stent was cost-effective (dominant) and highly cost saving to the NHS for both populations. For the variceal bleeding indication, when compared with EBL, TIPSS resulted in 0.22 additional QALYs, saved the NHS £1,301 per patient and had a 68% probability of being cost-effective. For the refractory ascites indication, when compared with LVP, TIPSS resulted in 0.526 additional QALYs, saved the NHS £17,983 per patient and had a 100% probability of being cost-effective. Conclusions TIPSS using a GORE® VIATORR® stent to manage patients with severe cirrhosis and RA or bleeding is expected to be cost-saving and improve patient outcomes. While TIPSS remains cost-saving and cost-effective in our base-case analysis for the management of high quality and adequately powered RCTs which also evaluate quality of life and health economics are required to inform robust economic analysis; mainly for the bleeding indication. Increased implementation of TIPSS is likely to improve patient outcomes and be cost saving to the NHS, particularly for the management of ascites.

Liver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial.To assess the utility of liver biopsy in the assessment of clinically severe AH METHODS: The histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores.The STOPAH trial recruited 1068 patients; biopsies were obtained in 182 (17%). One hundred and sixty-one biopsies were adequate for histological assessment and 140 (87%) were diagnostic for ASH. Only three biopsies (2%) did not have histological features of alcohol-related liver injury. In biopsies performed prior to randomisation, ASH was identified in 92.5% of patients meeting clinical trial definitions of severe AH. In biopsies with ASH, taken before or within 48 hours of randomisation, survival differences between Alcoholic Hepatitis Histological Score (AHHS) groups were not significant: comparison of mild / moderate (91%: 21 of 23 patients) with severe (78%: 29 of 37 patients) groups: P = 0.18. The AHHS was not superior to clinical scores of prognosis: area under the curve for 28-day mortality was 0.728, compared with 0.799 for the Glasgow alcoholic hepatitis score and 0.728 for the MELD score.Liver histology taken before treatment rarely changes the diagnosis in patients meeting strict criteria for a clinical diagnosis of AH. The AHHS is similar to clinical scores in determining prognosis. Clinical trial registration EudraCT reference number: 2009-013897-42. ISRCTN reference number: 88782125. MREC number: 09/MRE09/59.9143.

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.

The latest ‘Controversies in…’ series for the Frontline Gastroenterology Twitter debates addressed the challenges of managing patients with portal hypertension, facilitated by Hepatologist and Liver Transplant physician Dr David Patch from the Royal Free London. Key topics discussed include basic principles of managing a patient with variceal bleeding, techniques for treating oesophageal and ectopic varices, pitfalls of vasoactive therapy, indications for transjugular intrahepatic portosystemic shunt, and a brief discussion of portal vein thrombosis. This article aims to summarise key areas of discussion from the event.

'Static' prognostic models in alcoholic hepatitis, using data from a single time point, include the discriminant function (DF), Glasgow alcoholic hepatitis score (GAHS), the age, serum bilirubin, international normalized ratio and serum creatinine (ABIC) score and the model of end-stage liver disease (MELD). 'Dynamic' scores, incorporating evolution of bilirubin at seven days, include the Lille score. The aim of this study was to assess these scores' performance in patients from the STOPAH trial.Predictive performance of scores was assessed by area under the receiver operating curve (AUC). The effect of different therapeutic strategies upon survival was assessed by Kaplan-Meier analysis and tested using the log-rank test.A total of 1,068 patients were studied. The AUCs for the DF were significantly lower than for MELD, ABIC and GAHS for both 28- and 90-day outcomes: 90-day values were 0.670, 0.704, 0.726 and 0.713, respectively. 'Dynamic' scores and change in 'static' scores by Day 7 had similar AUCs. Patients with consistently low 'static' scores had low 28-day mortalities that were not improved with prednisolone (MELD25: 8.6%; ABIC6.71: 6.6%; GAHS9: 5.9%). In patients with high 'static' scores without gastrointestinal bleeding or sepsis, prednisolone reduced 28-day mortality (MELD: 22.2% vs. 28.9%, p = 0.13; ABIC 14.6% vs. 21%, p = 0.02; GAHS 21% vs. 29.3%, p = 0.04). Overall mortality from treating all patients with a DF ≥32 and Lille assessment (90-day mortality 26.8%) was greater than combining newer 'static' and 'dynamic' scores (90-day mortality: MELD/Lille 21.8%; ABIC/Lille 23.7%; GAHS/Lille 20.6%).MELD, ABIC and GAHS are superior to the DF in alcoholic hepatitis. Consistently low scores have a favourable outcome not improved with prednisolone. Combined baseline 'static' and Day 7 scores reduce the number of patients exposed to corticosteroids and improve 90-day outcome.Alcoholic hepatitis is a life-threatening condition. Several scores exist to determine the outcome of these patients as well as to identify those who may benefit from treatment. This study looked at the performance of existing scores in patients who had been recruited to the largest alcoholic hepatitis clinical trial: STOPAH. 'Static' scores are calculable at the start of assessment. The three newer static scores (ABIC, GAHS and MELD) were shown to be superior to the oldest score (DF). ABIC and GAHS could also identify patients who had a survival benefit 28 days after starting prednisolone treatment. 'Dynamic' scores relate to the change in disease over the first week of treatment. Combination of the 'static' scores 'with the 'dynamic' scores or change in 'static' scores allowed identification of patients who could benefit from prednisolone up to 90 days.

Purpose Transjugular intrahepatic portosystemic shunt (TIPS) creation is used to treat portal hypertension complications. Often the most challenging and time-consuming step in the procedure is the portal vein (PV) puncture. TIPS procedures are associated with prolonged fluoroscopy time and high patient radiation exposures. We measured the impact of transabdominal ultrasound guidance for PV puncture on duration of fluoroscopy time and dose. Methods We retrospectively analyzed the radiation dose for all TIPS performed over a four-year period with transabdominal ultrasound guidance for PV puncture (n=212, with 210 performed successfully and data available for 206); fluoroscopy time, dose area product (DAP) and skin dose were recorded. Results Mean fluoroscopy time was 12 min 9 s (SD, ±14 min 38 s), mean DAP was 40.3±73.1 Gy·cm2, and mean skin dose was 404.3±464.8 mGy. Conclusion Our results demonstrate that ultrasound-guided PV puncture results in low fluoroscopy times and radiation doses, which are markedly lower than the only published dose reference levels.

OBJECTIVES: Caval subtraction phase-contrast magnetic resonance imaging (PCMRI) noninvasive measurements of total liver blood flow (TLBF) and hepatic arterial (HA) flow have been validated in animal models and translated into normal volunteers, but not patients. This study aims to demonstrate its use in patients with liver cirrhosis, evaluate measurement consistency, correlate measurements with portal hypertension severity, and invasively validate TLBF measurements. MATERIALS AND METHODS: Local research ethics committee approval was obtained. Twelve patients (mean, 50.8 ± 3.1 years; 10 men) with histologically confirmed cirrhosis were recruited prospectively, undergoing 2-dimensional PCMRI of the portal vein (PV) and the infrahepatic and suprahepatic inferior vena cava. Total liver blood flow and HA flow were estimated by subtracting infrahepatic from suprahepatic inferior vena cava flow and PV flow from estimated TLBF, respectively. Invasive hepatic venous pressure gradient (HVPG) and indocyanine green (ICG) clearance TLBF were measured within 7 days of PCMRI. Bland-Altman (BA) analysis of agreement, coefficients of variation, and Pearson correlation coefficients were calculated for comparisons with direct inflow PCMRI, HVPG, and ICG clearance. RESULTS: The mean difference between caval subtraction TLBF and direct inflow PCMRI was 6.3 ± 4.2 mL/min/100 g (BA 95% limits of agreement, ±28.7 mL/min/100 g). Significant positive correlations were observed between HVPG and caval subtraction HA fraction (r = 0.780, P = 0.014), but not for HA flow (r = 0.625, P = 0.053), PV flow (r = 0.244, P = 0.469), or caval subtraction TLBF (r = 0.473, P = 0.141). Caval subtraction and ICG TLBF agreement was modest (mean difference, -32.6 ± 16.6 mL/min/100 g; BA 95% limits of agreement, ±79.7 mL/min/100 g), but coefficients of variation were not different (65.7% vs 48.1%, P = 0.28). CONCLUSIONS: In this proof-of-principle study, caval subtraction PCMRI measurements are consistent with direct inflow PCMRI, correlate with portal hypertension severity, and demonstrate modest agreement with invasive TLBF measurements. Larger studies investigating the clinical role of TLBF and HA flow measurement in patients with liver disease are justified.

Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.

Introduction Non-alcoholic fatty liver disease (NAFLD) accounts for 15–20% of orthotopic liver transplants (OLT) in the United Kingdom. Index presentations with cirrhotic decompensation impact morbidity and mortality and represents missed opportunities for preventive treatment leaving OLT or palliation as the only options. We aimed to determine the proportion of patients undergoing OLT assessment for NAFLD in whom the first presentation was an episode of cirrhotic decompensation by expanding upon our previous audit. Methods Patient records were interrogated for all NAFLD patients undergoing assessment for OLT at the Royal Free London NHS Foundation Trust liver transplant unit between January 2003 and December 2017. Demographic, clinical, laboratory and outcome data were extracted. Those with an index presentation of jaundice, ascites, variceal bleeding, encephalopathy or HCC at presentation were classified as ‘decompensated’. Results Data were available for 81 patients with NAFLD as the primary diagnosis. At first presentation to healthcare with chronic liver disease (CLD) 52 patients had decompensated cirrhosis while 29 had compensated cirrhosis. A decompensation event diagnosed in secondary care represented the first presentation with liver disease for 91·7% of patients compared to 52·6% referred from primary care. Cirrhosis was not suspected at the time of referral to hospital in 24·7% of patients subsequently assessed for OLT. OLT was performed in 43 patients. Thirty-one (72·1%) of these patients were decompensated at first presentation compared to 55·3% who were not transplanted. Four deaths occurred in OLT recipients within 6 months of transplantation, all of whom presented for the first time with decompensated cirrhosis. figure 1 illustrates the difference in survival between those patients who did and did not undergo OLT. Patients who underwent OLT had a significantly longer mean survival time of 9·81 years (95% CI 8·51–11·12) compared to those who did not undergo OLT 4·62 years (95% CI 3·35–5·89, p Conclusions Most patients undergoing assessment for OLT for NAFLD had decompensated cirrhosis at their first diagnosis of CLD. These data underline the association between the late diagnosis of CLD in NAFLD with emergency hospitalisation and mortality and reinforce the necessity for greater awareness and earlier diagnosis of cirrhosis in NAFLD.

Introduction Recent literature supports the paradigm of a rebalanced, although fragile, haemostasis equilibrium in compensated cirrhosis, poorly reflected by standard coagulation tests. We performed thromboelastography (TEG) to evaluate the global haemostatic profile of patients with stable decompensated cirrhosis, assessing for correlation with liver disease severity. We examined whether portal venous blood displayed an increased pro-thrombotic profile in comparison to peripheral and hepatic venous blood, potentially contributing to the high incidence of portal venous thrombosis in cirrhosis. Methods 18 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt procedures for refractory ascites or previous variceal bleeding were prospectively studied. Exclusion criteria included recent anticoagulation, infection or variceal bleeding (within two weeks), haematological disorders, or splanchnic venous thrombosis. Reaction time (R), kinetic time (K), alpha-angle, and maximum amplitude (MA) were measured in citrated portal, hepatic and peripheral venous blood using TEG Haemostasis Analyser 5000. Correlations were assessed with platelet count, prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration; and evaluated against liver disease severity scores. Statistical analysis was performed using SPSSv24. Results Patients were predominantly male (61%), with Child Pugh B cirrhosis (89%), mean MELD score 11.6±3.6. A frequent hypercoagulable profile was demonstrated (shortened R-time in 89% of patients, shortened K-time in 69%, increased alpha-angle in 81%), despite a prolonged INR, PT, APTT in 56–61% of patients. R-time (reflecting soluble clotting factors concentration) did not significantly correlate with INR or PT. MA (associated with platelet number/function) was normal in 83% of patients, despite thrombocytopenia present in 56%. Portal venous blood displayed a comparable TEG profile to peripheral and hepatic venous blood. The MA parameter of TEG demonstrated the strongest correlation with UKELD (r=-0.7, p=0.001) and MELD (r=-0.6, p=0.02) scores. Conclusion Our cohort of decompensated cirrhotic patients displayed an overall hypercoagulable TEG profile, despite co-existing thrombocytopenia and a prolonged INR, PT and APTT, demonstrating poor representation of the global haemostatic profile by standard coagulation tests. TEG in peripheral venous blood accurately reflected the haemostatic profile of portal venous blood. TEG parameters correlated with liver disease severity scores in spite of poor representation by INR within these scores, thus the potential benefit of utilising TEG for liver disease severity assessment in routine clinical practice warrants further evaluation.

Background Anticoagulation alone in acute, extensive portomesenteric vein thrombosis (PVT) does not always result in spontaneous clot lysis, and leaves the patient at risk of complications including intestinal infarction and portal hypertension. Aim To develop a new standard of care for patients with acute PVT and evidence of intestinal ischaemia. Methods We present a case series of patients with acute PVT and evidence of intestinal ischaemia plus ongoing symptoms despite initial systemic anticoagulation, who were treated with a thrombolysis protocol between 2014 and 2019. This stepwise protocol initially uses low-dose systemic alteplase, and in patients with ongoing abdominal pain, and no evidence of radiological improvement, is followed by local clot dissolution therapy (CDT) through a TIPSS. Outcomes and safety were assessed. Results Twenty-two patients were included. The mean age was 44.6 (standard deviation [SD] 16.0) years, and 64% had an identifiable prothrombotic risk factor. All patients had intestinal wall oedema and 77% had complete occlusion of all portomesenteric veins. Systemic thrombolysis was started 18.7 (SD 11.2) days after the onset of symptoms. 55% of patients underwent TIPSS insertion for CDT. At the end of treatment, symptoms resolved in 91% of patients and recanalisation in 86%. Only one patient required resection for intestinal ischaemia, and there were no deaths. Major complications occurred in two patients (9%). Conclusions Our stepwise protocol is effective, resulting in good recanalisation rates. It can be commenced early while organising transfer to a centre capable of performing local CDT.

Background and Aims Small-bowel varices (SBVs) are an uncommon consequence of portal hypertension. Radiologic intervention is usually considered for first-line management. When radiologic intervention is not possible, management options become very limited. The aim of this study was to evaluate the usefulness of double-balloon enteroscopy (DBE)-facilitated cyanoacrylate-injection endotherapy of SBVs. Methods This was a retrospective review of DBE-facilitated cyanoacrylate-injection endotherapy of SBVs (December 2015 to October 2016). Results Ten DBEs were performed in 6 patients (4 women; median age, 68.5 years). No radiologic or surgical options were deemed feasible. Thirteen nests of SBVs were identified and injected with cyanoacrylate glue without hemorrhagic or embolic adverse events. At the 30-day follow-up after therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding; this was managed conservatively. One patient presented with acute GI bleeding 7 months later, and a repeat DBE with cyanoacrylate-injection endotherapy was successfully performed. One patient succumbed to his underlying advanced cholangiocarcinoma after 2 months. The remaining patients had a median follow-up of 12 months without any recurrent GI bleeding. Conclusions DBE-facilitated cyanoacrylate-injection endotherapy of SBVs appears to be a safe and effective option when other first-line options are not feasible.

Background/aims Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients. Methods We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995-2013) and survived at least 1-year post-LT or died before that due to a major CVS complication. Results Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360). Conclusions Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT.

Background: Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented. Methods: The associations of nutritional status and sarcopenia with post-transplant infections, requirement for mechanical ventilation, intensive care (ICU) and hospital stay, and 1year mortality were assessed in 232 consecutive transplant recipients. Nutritional status and sarcopenia were assessed using the Royal Free Hospital-Global Assessment (RFH-GA) tool and the L3-psoas muscle index (L3-PMI) on CT, respectively. Results: A wide range of RFH-SGA and L3-PMI were observed within similar Model for End-stage Liver Disease (MELD) sub-categories. Malnutrition and sarcopenia were independent predictors of all outcomes. Post-transplant infections were associated with MELD (OR=1.055, 95%CI=1.002-1.11) and severe malnutrition (OR=6.55, 95%CI=1.99-21.5); ventilation>24h with MELD (OR=1.1, 95%CI=1.036-1.168), severe malnutrition (OR=8.5, 95%CI=1.48-48.87) and suboptimal donor liver (OR=2.326, 95%CI=1.056-5.12); ICU stay>5days, with age (OR=1.054, 95%CI=1.004-1.106), MELD (OR=1.137, 95%CI=1.057-1.223) and severe malnutrition (OR=7.46, 95%CI=1.57-35.43); hospital stay>20days with male sex (OR=2.107, 95%CI=1.004-4.419) and L3-PMI (OR=0.996, 95%CI=0.994-0.999); 1year mortality with L3-PMI (OR=0.996, 95%CI=0.992-0.999). Patients at the lowest L3-PMI receiving suboptimal grafts had longer ICU/hospital stay and higher incidence of infections. Conclusions: Malnutrition and sarcopenia are associated with early post-liver transplant morbidity/mortality. Allocation indices do not include nutritional status and may jeopardize outcomes in nutritionally compromised individuals.

Introduction Small bowel varices (SBV) are a rare consequence of portal hypertension and could lead to life-threatening mid-gut bleeding. Radiological intervention (RI) is usually considered first line management (e.g. Trans-jugular intrahepatic portosystemic shunting (TIPS), stenting of occluded mesenteric veins±embolisation of culprit varices). In cases where RI is impossible, management options become very limited. This multicentre case series evaluated the usefulness of double-balloon enteroscopy (DBE) assisted cyanoacrylate injection of SBV. Methods Retrospective review of DBE facilitated cyanoacrylate injection of SBV (December 2015 to October 2016). Demographic, clinical, endoscopic and radiological findings, interventions and follow-up data were analysed. Results Ten DBEs were performed in 6 patients (4 women, median age: 68.5 years). Five patients had previous surgery (hemi-hepatectomy (n=2); SB resection (n=2); appendicitis with peritonitis (n=1)); one patient had a history of intra-abdominal sepsis in childhood causing portal vein thrombosis and one had cryptogenic thrombosis of the portal and the mesenteric vein. No radiological or surgical options were deemed feasible in any case. SBV were diagnosed at capsule endoscopy and triple phase CT mesenteric angiography. At DBE, a total of 13 nests of SBV were identified and injected with cyanoacrylate glue. There were no haemorrhagic or embolic complications but 1 patient developed an infection of a congenital urachal cyst, which was treated successfully with antibiotics. All patients underwent DBEs via the anterograde route, 2 patients required bi-directional DBE for treatment of both proximal and distal SBV and in total 2 patients required a repeat DBE for further treatment of SBV. At 30 day follow-up post-therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding treated conservatively. One patient presented with acute gastrointestinal bleeding 7 months later and a repeat DBE with cyanoacrylate injection therapy was successfully performed. One patient was lost to follow-up. The remaining patients had 12 months of follow-up without any recurrent gastrointestinal bleeding. Conclusion Cyanoacrylate injection therapy of SBV at DBE appears to be a safe and effective management strategy for this condition when other first-line options are not feasible.

Introduction Vitamin D deficiency and reduced BMD are highly prevalent in patients with advanced chronic liver disease. For bisphosphonate treatment for osteoporosis to be effective vitamin D levels must be replete. Moreover, vitamin D deficiency has been associated with an increased risk of infections and increased rejection rates following liver transplantation. The optimal dose and route of vitamin D replacement in cirrhosis is unknown. BSG guidance currently recommends 800 IU/day orally for all patients with cirrhosis/cholestatic liver disease. Methods Retrospective review of 218 cirrhotic patients undergoing evaluation for liver transplant between 2016 and 2017. Vitamin D ‘severe deficiency’ was defined as 50 ng/ml. Response to oral vitamin D therapy was recorded. Results Out of 218 patients, 128/218 (59%) had low Vitamin D levels with 25% (n=55) ‘severely deficient’ and 33% (n=73) ‘deficient’. Overall 33 patients with levels 50 ng/ml received replacement therapy. (p=0.86) Median daily dose of Vitamin D replacement was 2800 units/day (IQR 800–2800) in 50 ng/dl group. No significant difference in dosing between these groups (p=0.12). Data on vitamin D levels pre and post 3 months of treatment with Vitamin D therapy were available in 58 patients. Patients received either 400IU/day (n=6), 800–1600IU/day (n=28) or >1600 IU/Day (n=24). Median delta change in vitamins D levels in the 3 groups were −3 ng/ml, −1 ng/ml and 12 ng/ml over the 3 month treatment period. An average daily dose of >1600 IU/day Resulted in a significantly greater increase in Vitamin D levels when compared to doses When those patients with Vitamin D levels of 50 ng/dl and no significant difference was found between dosages of vitamin D administered. Conclusion Vitamin D deficiency is prevalent, affecting over 50% of patients with advanced cirrhosis. Oral vitamin D replacement therapy is ineffective in cirrhotics at repleting stores over a 3 month period irrespective of dose given. Future evaluation of efficacy of IM administration in this unique cohort of patients is urgently needed to evaluate if this allows normalisation of Vitamin D levels.

Background Transjugular intrahepatic portosystemic shunt (TIPS) has proven clinical efcacy as rescue therapy for cirrhotic patients with acute portal hypertensive bleeding who fail endoscopic treatment. Aims To investigate predictive factors of 6-week and 1-year mortality in patients undergoing salvage TIPS for refractory portal hypertensive bleeding. Methods A total of 144 consecutive patients were retrospectively evaluated. Three logistic regression multivariate models were estimated to individualize prognostic factors for 6-week and 12-month mortality. Log-rank test was used to evaluate survival according to Child–Pugh classes and Bureau’s criteria. Results Mean age 51±10 years, 66% male, mean MELD 18.5±8.3, Child–Pugh A/B/C 8%/38%/54%. TIPS failure occurred in 23(16%) patients and was associated with pre-TIPS portal pressure gradient and pre-TIPS intensive care unit stay. Six-week and 12-month mortality was 36% and 42%, respectively. Pre-TIPS intensive care unit stay, MELD, and Child–Pugh score were independently associated with mortality at 6 weeks. Independent predictors of mortality at 12 months were pre-TIPS intensive care unit stay and Child–Pugh score. Conclusions In this large cohort of patients undergoing salvage TIPS, MELD and Child–Pugh scores were predictive of short- and long-term mortality, respectively. Pre-TIPS intensive care unit stay was independently associated with TIPS failure and mortality at 6 weeks and 12 months. Salvage TIPS is futile in patients with Child–Pugh score of 14–15.