Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.

Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site's standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher's chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017-2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04-2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.

Textbook Outcome After Trans-arterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: Textbook Outcome (TO) is inclusive of quality indicators and it not been provided for trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data on treatment-naïve HCC patients receiving TACE from 10 centers were reviewed. TO was defined as "no post-TACE grade 3-4 complications, no prolonged hospital stay (defined as a post-procedure stay ≤ 75th percentile of the median values from the total cohort), no 30-day mortality/readmission and the achievement of an objective response (OR) at post-TACE imaging." Grade of adverse event was classified according to the Common Terminology Criteria for Adverse Events and short-term efficacy was assessed by response. Pooled estimates were calculated to account for hospital's effect and risk-adjustment was applied to allow for diversity of patients in each center. RESULTS: A total of 1124 patients (2014-2018) fulfilling specific inclusion criteria were included. Baseline clinical features showed considerable heterogeneity (I2 > 0.75) across centers. TACE-related mortality was absent in 97.6%, readmission was not required after 94.9% of procedures, 91.5% of patients had no complication graded 3-4, 71.8% of patients did not require prolonged hospitalization, OR of the target lesion was achieved in 68.5%. Risk-adjustment showed that all indicators were achieved in 43.1% of patients, and this figure was similar across centers. The median overall survival for patients who achieved all indicators was 33.1 months, 11.9 months longer than for patients who did not. CONCLUSIONS: A useful benchmark for TACE in HCC patients has been developed, which provides an indication of survival and allows for a comparison of treatment quality across different hospitals.

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence.

Narrow-band imaging for the diagnosis of nonerosive reflux disease: an international, multicenter, randomized controlled trial.

BACKGROUND AND AIMS: We examined the accuracy of narrow-band imaging (NBI) findings in nonerosive reflux disease (NERD) patients compared with control subjects and the impact of proton pump inhibitor (PPI) therapy on these mucosal changes in a multicenter, double-blind, randomized controlled trial. METHODS: NERD patients (typical symptoms using a validated GERD questionnaire, absence of erosive esophagitis, and abnormal 48-hour pH study) and control subjects underwent high-definition white-light endoscopy followed by NBI and biopsy sampling of the distal esophagus. Then, NERD patients were randomized to esomeprazole 40 mg/day or placebo for 8 weeks, followed by repeat endoscopy. The presence of distal esophageal mucosal changes on NBI were recorded at baseline and after treatment: intrapapillary capillary loops (IPCLs; number, dilation, and tortuosity), microerosions, increased vascularity, columnar islands, and ridge/villous pattern (RVP) above the squamocolumnar junction. RESULTS: Of 122 screened, 21 NERD and 21 control subjects were identified (mean age, 49.5 ± 14.6 years; 62% men; and 85% white). The combination of IPCL tortuosity, RVP, and microerosions (62% vs 19%, P < .05) had a high specificity (86%) and moderate sensitivity (60%) for NERD with an area under the curve of .74. In 10 NERD patients treated with PPIs, resolution of microerosions was most significant (P = .047) compared with placebo (n = 11). RVP resolved in all NERD patients after therapy (P = .02) and correlated with acid exposure time (P = .004). Papillary length (P = .02) and basal cell thickness (P = .02) significantly correlated with a combination of IPCL tortuosity, RVP, and microerosions. CONCLUSIONS: In this randomized controlled trial, RVP on NBI demonstrated a high specificity, correlated with acid exposure time, and improved with PPI therapy, suggesting that it could be used as a surrogate marker for diagnosis of NERD. (Clinical trial registration number: NCT02081404.).

Characterisation of dysplastic liver nodules using low-pass DNA sequencing and detection of chromosome arm-level abnormalities in blood-derived cell-free DNA.

High-grade dysplasia carries significant risk of transformation to hepatocellular carcinoma (HCC). Despite this, at the current standard of care, all non-malignant hepatic nodules including high-grade dysplastic nodules are managed similarly. This is partly related to difficulties in distinguishing high-risk pathology in the liver. We aimed to identify chromosome arm-level somatic copy number alterations (SCNAs) that characterise the transition of liver nodules along the cirrhosis-dysplasia-carcinoma axis. We validated our findings on an independent cohort using blood-derived cell-free DNA. A repository of non-cancer DNA sequences obtained from patients with HCC (n = 389) was analysed to generate cut-off thresholds aiming to minimise false-positive SCNAs. Tissue samples representing stages from the multistep process of hepatocarcinogenesis (n = 184) were subjected to low-pass whole genome sequencing. Chromosome arm-level SCNAs were identified in liver cirrhosis, dysplastic nodules, and HCC to assess their discriminative capacity. Samples positive for 1q+ or 8q+ arm-level duplications were likely to be either HCC or high-grade dysplastic nodules as opposed to low-grade dysplastic nodules or cirrhotic tissue with an odds ratio (OR) of 35.5 (95% CI 11.5-110) and 16 (95% CI 6.4-40.2), respectively (p < 0.0001). In an independent cohort of patients recruited from Nottingham, UK, at least two out of four alterations (1q+, 4q-, 8p-, and 8q+) were detectable in blood-derived cell-free DNA of patients with HCC (n = 22) but none of the control patients with liver cirrhosis (n = 9). Arm-level SCNAs on 1q+ or 8q+ are associated with high-risk liver pathology. These can be detected using low-pass sequencing of cell-free DNA isolated from blood, which may be a future early cancer screening tool for patients with liver cirrhosis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.

BACKGROUND AND AIMS: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10-6 ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10-4 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10-26 ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10-23 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (ORallelic , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10-4 ). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.

Validation of the AASLD recommendations for classification of oesophageal varices in clinical practice.

BACKGROUND & AIMS: The American Association for the Study of Liver Diseases recommends the use of a 2-grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3-grade classification (grade 1 'small', grade 2 'medium', grade 3 'large') among operators of variable experience. METHODS: High-definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra-observer agreement. RESULTS: Interobserver agreement (all observers) using the 2-grade and the 3-grade system was k = 0.71 (95% CI: 0.64-0.78) and k = 0.73 (95% CI: 0.66-0.79) respectively. When using the 2-grade system, intra-observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86-0.91), k = 0.72 (95% CI: 0.67-0.77), and k = 0.74 (95% CI: 0.67-0.8) respectively. With the 3-grade system; intra-observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87-0.92), k = 0.73 (95% CI: 0.68-0.78), k = 0.77 (95% CI: 0.71-0.82) respectively. CONCLUSIONS: There was no difference in OA between the 2-grade and 3-grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV.

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

BACKGROUND AND AIMS: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.

The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation.

BACKGROUND: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and new-onset DM on liver transplantation (LT) recipients. METHODS: A single-center retrospective analysis of prospectively collected data of LT recipients (1990-2015) was undertaken. RESULTS: Of the 2209 patients, 13% (n = 298) had Pre-DM, 16% (n = 362) developed post-transplant diabetes mellitus (PTDM), 5% (n = 118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n = 1431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM were similar to that of patients with Pre-DM. Incidence of PTDM peaked during the first year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), nonalcoholic fatty liver disease and the use of tacrolimus and sirolimus were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycemic control throughout the follow-up period. Those who developed t-HG seem to have a unique characteristic compared with others. Overall, 9%, 5%, and 8% of patients developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, retransplantation, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM. CONCLUSIONS: In this largest nonregistry study, patients with Pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up.

Healthcare costs of transarterial chemoembolization in the treatment of hepatocellular carcinoma.

BACKGROUND: A meta-analysis comparing drug-eluting beads transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (cTACE) has recently been published. On balance, no significant differences were found in terms of objective response and overall survival. The impact on healthcare costs had been studied in small series based on a hypothetical model and was in favor of DEB-TACE. We aimed to evaluate and compare health-care costs and effectiveness of both modalities in a cohort of patients from Nottingham, UK. METHODS: Using a dedicated radiology database, we identified all patients who had undergone cTACE or DEB-TACE between 2006 and 2012 at a single tertiary referral center based in Nottingham. We collected clinical data, including treatment response, postprocedure complications and 30-day mortality. Costing models were constructed to present both our local hospital perspective as well as the national health service position. RESULTS: During our study period, 101 procedures were performed on 43 patients (76 cTACE procedures on 26 patients and 25 DEB-TACE procedures on 17 patients). Overall, 11/26 in cTACE and 5/17 in DEB-TACE group had progressive disease (p=0.52). Adverse events were seen in 6/76 cTACE compared with 7/25 DEB-TACE group (p=0.16). Based on the predetermined standard pathway there was an unadjusted average cost difference of £3770.30 (TACE =£9070.44, DEB-TACE =£5300.14) in favor of the DEB-TACE. Results from our costing models indicated a £2715.33 (95% CI £580.88-4849.77) cost difference in favor of the same procedure. CONCLUSIONS: Even when the extra costs of DEB-TACE were considered, the overall treatment costs per patient were lower in relation to cTACE.

Patient understanding of liver cirrhosis and improvement using multimedia education.

OBJECTIVE: For patients to engage with the long-term management of liver cirrhosis, sufficient understanding of their condition is essential. The aim of this study was to assess baseline patient knowledge and to test whether a condition-specific multimedia screencast could improve this. DESIGN: Service quality improvement study. SETTING: A UK tertiary liver centre. Patients were recruited during 12 general hepatology outpatient clinics. PATIENTS: Fifty-two patients with liver cirrhosis were included. Sixty-two per cent were male; their median age was 56 years and their median clinic attendance period was 3 years. INTERVENTIONS: Participants completed a baseline questionnaire assessing their knowledge of the management and complications of cirrhosis. They then watched a tailored screencast discussing this condition, which had been developed by expert hepatologists in collaboration with patient representatives. Knowledge was reassessed using a new copy of the original questionnaire after an interval of at least one month. MAIN OUTCOME MEASURES: Patient scores on knowledge questionnaires at baseline and follow-up. RESULTS: Fifty-two patients achieved a median score of 25.0% before viewing the screencast. Thirty-five patients then completed a follow-up questionnaire after an interval period. The median questionnaire score in this group improved from 25.0% to 66.7%; an increase of 41.7% compared with baseline (p<0.001). CONCLUSIONS: Despite regular review at a specialist clinic, participants had poor baseline knowledge of liver cirrhosis. Delivering information by screencast led to a significant improvement. We therefore present an effective way to empower patients with accurate, up-to-date and retainable information that can easily be translated to many other conditions.

Screening for hepatocellular carcinoma: patient selection and perspectives.

Hepatocellular carcinoma (HCC) develops on the background of liver cirrhosis often from multiple, simultaneous factors. The diagnosis of a single small HCC comes with good prognosis and provides a potential for cure. In contrast, the diagnosis of multifocal, large HCC has high mortality and poor prognosis. Unfortunately, the majority of HCC is diagnosed at such late stages. A surveillance program endorsed by regional liver societies involves six-monthly ultrasound surveillance of at-risk patients. This had been in action for the last two decades. It has led to marked increase in the proportion of patients presenting with small unifocal nodules found on surveillance. The development of tools to enhance our ability in optimizing available surveillance is likely to improve the prognosis of patients with HCC. In this review, we discuss the difficulties in utilizing HCC surveillance and possible means of improvement.