Guidance document: risk assessment of patients with cirrhosis prior to elective non-hepatic surgery.

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.

A Review of Risk Scores within Upper Gastrointestinal Bleeding.

Upper gastrointestinal bleeding is a common medical emergency. Thorough initial assessment and appropriate resuscitation are essential to stabilise the patient. Risk scores provide an important tool to discriminate between lower- and higher-risk patients. Very low-risk patients can be safely discharged for out-patient management, while higher-risk patients can receive appropriate in-patient care. The Glasgow Blatchford Score, with a score of 0-1, performs best in the identification of very low-risk patients who will not require hospital based intervention or die, and is recommended by most guidelines to facilitate safe out-patient management. The performance of risk scores in the identification of specific adverse events to define high-risk patients is less accurate, with no individual score performing consistently well. Ongoing developments in the use of machine learning models and artificial intelligence in predicting poor outcomes in UGIB appear promising and will likely form the basis of dynamic risk assessment in the future.

Hepatocellular Carcinoma Risk Scores Predict Patients Under Surveillance at Low Risk of Benefit and High Risk of Harm.

AIMS: Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. Multiple risk scores aim to stratify HCC risk, potentially allowing individualized surveillance strategies. We sought to validate four risk scores and quantify the consequences of surveillance via the calculation of numbers needed to benefit (NNB) and harm (NNH) according to classification by risk score strata. METHODS: Data were collected on 482 patients with cirrhosis during 2013-2014, with follow-up until 31/12/2019. Risk scores (aMAP, Toronto risk index, ADRESS HCC, HCC risk score) were derived from index clinic results. The area under the receiving operating characteristic curve (AUC) was calculated for each. Additionally, per-risk strata, NNB was calculated as total surveillance ultrasounds per surveillance diagnosed early HCC (stage 0/A) and NNH as total ultrasounds performed per false positive (abnormal surveillance with normal follow-up imaging). RESULTS: 22 (4.6%) patients developed HCC. 77% (17/22) were diagnosed through surveillance, of which 13/17 (76%) were early stage. There were 88 false positives and no false negatives (normal surveillance result however subsequent HCC detection). Overall NNB and NNH were 241 and 36, respectively. No score was significantly superior using AUC. Patients classified as low risk demonstrated no surveillance benefit (AMAP, THRI) or had a high NNB of > 300/900 (ADRESS HCC, HCC risk score), with low NNH (24-38). CONCLUSION: Given the lack of benefit and increased harm through false positives in low-risk groups, a risk-based surveillance strategy may have the potential to reduce patient harm and increase benefit from HCC surveillance. CLINICAL TRIALS REGISTRATION: This was not a clinical trial and the study was not pre-registered.

Rebleeding in peptic ulcer bleeding - a nationwide cohort study of 19,537 patients.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB). The associated prognosis remains rather unclear because previous studies generally also included non-ulcer lesions. OBJECTIVE: We aimed to identify predictors for rebleeding; clarify the prognostic consequence of rebleeding; and develop a score for predicting rebleeding. METHODS: Nationwide cohort study of consecutive patients presenting to hospital with PUB in Denmark from 2006-2014. Logistic regression analyses were used to identify predictors for rebleeding, evaluate the association between rebleeding and 30-day mortality, and develop a score to predict rebleeding. Patients with persistent bleeding were excluded. RESULTS: Among 19,258 patients (mean age 74 years, mean ASA-score 2.4), 10.8% rebled, and 10.2% died. Strongest predictors for rebleeding were endoscopic high-risk stigmata of bleeding (Odds Ratio (OR): 2.12 [95% Confidence Interval (CI): 1.91-2.36]), bleeding from duodenal ulcers (OR: 1.87 [95% CI: 1.69-2.08]), and presentation with hemodynamic instability (OR: 1.55 [95% CI: 1.38-1.73]). Among patients with all three factors (7.9% of total), 24% rebled, 50% with rebleeding failed endoscopic therapy, and 23% died. Rebleeding was associated with increased mortality (OR: 2.04 [95% CI: 1.78-2.32]). We were unable to develop an accurate score to predict rebleeding. CONCLUSION: Rebleeding occurs in ∼10% of patients with PUB and is overall associated with a two-fold increase in 30-day mortality. Patients with hemodynamic instability, duodenal ulcers, and high-risk endoscopic stigmata are at highest risk of rebleeding. When rebleeding occurs in such patients, consultation with surgery and/or interventional radiology should be obtained prior to repeat endoscopy.

Increasing the low-risk threshold for patients with upper gastrointestinal bleeding during the COVID-19 pandemic: a prospective, multicentre feasibility study.

Objective: During the COVID-19 pandemic, we extended the low-risk threshold for patients not requiring inpatient endoscopy for upper gastrointestinal bleeding (UGIB) from Glasgow Blatchford Score (GBS) 0-1 to GBS 0-3. We studied the safety and efficacy of this change. Methods: Between 1 April 2020 and 30 June 2020 we prospectively collected data on consecutive unselected patients with UGIB at five large Scottish hospitals. Primary outcomes were length of stay, 30-day mortality and rebleeding. We compared the results with prospective prepandemic descriptive data. Results: 397 patients were included, and 284 index endoscopies were performed. 26.4% of patients had endoscopic intervention at index endoscopy. 30-day all-cause mortality was 13.1% (53/397), and 33.3% (23/69) for pre-existing inpatients. Bleeding-related mortality was 5% (20/397). 30-day rebleeding rate was 6.3% (25/397). 84 patients had GBS 0-3, of whom 19 underwent inpatient endoscopy, 0 had rebleeding and 2 died. Compared with prepandemic data in three centres, there was a fall in mean number of UGIB presentations per week (19 vs 27.8; p=0.004), higher mean GBS (8.3 vs 6.5; p<0.001) with fewer GBS 0-3 presentations (21.5% vs 33.3%; p=0.003) and higher all-cause mortality (12.2% vs 6.8%; p=0.02). Predictors of mortality were cirrhosis, pre-existing inpatient status, age >70 and confirmed COVID-19. 14 patients were COVID-19 positive, 5 died but none from UGIB. Conclusion: During the pandemic when services were under severe pressure, extending the low-risk threshold for UGIB inpatient endoscopy to GBS 0-3 appears safe. The higher mortality of patients with UGIB during the pandemic is likely due to presentation of a fewer low-risk patients.

International multicenter study comparing demographics, therapy and outcomes in bleeding from Mallory Weiss tears and peptic ulcers.

Background and study aims Mallory Weiss tears (MWTs) are relatively uncommon causes of upper gastrointestinal bleeding (UGIB), and patients are generally considered at low risk of poor outcome, although data are limited. There is uncertainty about use of endoscopic therapy. We aimed to describe and compare an international cohort of patients presenting with UGIB secondary to MWT and peptic ulcer bleeding (PUB). Patients and methods From an international dataset of patients undergoing endoscopy for acute UGIB at seven hospitals, we assessed patients with MWT bleeding, including the endoscopic stigmata and endoscopic therapy applied. We compared baseline parameters, rebleeding rate, and 30-day mortality between patients with MWT and PUB. Results A total of 3648 patients presented with UGIB, 125 of whom (3.4 %) had bleeding from a MWT. Those patients were younger (61 vs 69 years, P  < 0.0001) and more likely to be men (66 % vs 53 %, P  = 0.006) compared to the patients PUB. The most common endoscopic stigmata seen in MWTs were oozing blood (26 %) or clean base (26 %). Of the patients with MWT, 53 (42 %) received endoscopic therapy. Forty-eight of them (90 %) had epinephrine injections and 25 (48 %) had through-the-scope clips. The rebleeding rate was lower in MWT patients compared with PUB patients (4.9 % vs 12 %, P  = 0.016), but mortality was similar (5.7 vs 7.0 %, P  = 0.71). Conclusions Although patients presenting with MWT were younger, with a lower rebleeding rate, their mortality was similar to that of patients with PUB. Endoscopic therapy was applied to 42 % MWT patients, with epinephrine injection as the most common modality.

Carvedilol versus endoscopic band ligation for secondary prophylaxis of variceal bleeding-long-term follow-up of a randomised control trial.

BACKGROUND AND AIMS: Carvedilol reduces rates of variceal bleeding and rebleeding by lowering portal pressure. However, an associated pleiotropic survival benefit has been proposed. We aimed to assess long-term survival in a cohort of patients previously randomised to receive either carvedilol or endoscopic band ligation (EBL) following oesophageal variceal bleeding (OVB). METHODS: The index study randomised 64 cirrhotic patients with OVB between 2006 and 2011 to receive either carvedilol or EBL. Follow-up was undertaken to April 2020 by review of electronic patient records. The primary outcome was survival. Other outcomes including variceal rebleeding and liver decompensation events were compared. RESULTS: 26 out of 33 participants received carvedilol in the follow-up period and 28 out of 31 attended regular EBL sessions. The median number of follow-up days for all patients recruited was 1459 (SE = 281.74). On the intention to treat analysis, there was a trend towards improved survival in the carvedilol group (p = 0.09). On per-protocol analysis, carvedilol use was associated with improved long-term survival (p = 0.005, HR 3.083, 95% CI 1.397-6.809), fewer liver-related deaths (0% vs 22.57%, p = 0.013, OR ∞, 95%CI 1.565-∞) and fewer admissions with decompensated liver disease (12% vs 64.29%, p = 0.0002, OR 13.2, 95% CI 3.026-47.23) compared to the EBL group. There was no statistically significant difference in variceal rebleeding rates. CONCLUSION: Following OVB in cirrhotic patients, carvedilol use is associated with survival benefit, fewer liver-related deaths and fewer hospital admissions with decompensated liver disease. Further studies are needed to validate this finding.

Update on the management of upper gastrointestinal bleeding.

Upper gastrointestinal bleeding is a common emergency presentation requiring prompt resuscitation and management. Peptic ulcers are the most common cause of the condition. Thorough initial management with a structured approach is vital with appropriate intravenous fluid resuscitation and use of a restrictive transfusion threshold of 7-8 g/dL. Pre-endoscopic scoring tools enable identification of patients at high risk and at very low risk who might benefit from specific management. Endoscopy should be carried out within 24 h of presentation for patients admitted to hospital, although optimal timing for patients at a higher risk within this period is less clear. Endoscopic treatment of high risk lesions and use of subsequent high dose proton pump inhibitors is a cornerstone of non-variceal bleeding management. Variceal haemorrhage results in higher mortality than non-variceal haemorrhage and, if suspected, antibiotics and vasopressors should be administered urgently, before endoscopy. Oesophageal variceal bleeding requires endoscopic band ligation, whereas bleeding from gastric varices requires thrombin or tissue glue injection. Recurrent bleeding is managed by repeat endoscopic treatment. If uncontrolled bleeding occurs, interventional radiological embolisation or surgery is required for non-variceal bleeding or transjugular intrahepatic portosystemic shunt placement for variceal bleeding.

The association between deprivation and the incidence and survival of patients with hepatocellular carcinoma in the West of Scotland.

INTRODUCTION: This study set out to examine the association between deprivation and the incidence of HCC and survival following diagnosis in the West of Scotland. METHODS: Data were gathered on patients from the prospective West of Scotland regional HCC database from November 2014 to August 2017. Patients were included if they had a new diagnosis of HCC. Data on deprivation were taken from the Scottish Index of Multiple Deprivation (SIMD) 2016. RESULTS: 357 patients were included in the study. There was a higher incidence rate in patients in SIMD quintile 1 (most deprived) compared with quintile 5 (least deprived) (8.4 vs 4.3 per 100,000, respectively, p < 0.0002). There was no difference in stage at diagnosis, treatment intent, or survival, between patients in the most deprived and least deprived quintiles (median survival 368 days vs 325 days, p = 0.8). CONCLUSION: Living in the most deprived areas of the West of Scotland was associated with approximately a twofold increase in the incidence of HCC. However, in contrast to previous research, there was no difference in survival following diagnosis between patients living in the most and least deprived areas.

The Value of Quantitative Faecal Immunochemical Testing as a Prioritisation Tool for the Endoscopic Investigation of Patients With Iron Deficiency.

Difficulty in providing endoscopy for patients with iron deficiency anaemia (IDA) during the COVID-19 pandemic has highlighted the requirement for a prioritisation tool. We aimed to test the validity of qFIT as a prioritisation tool in patients with iron deficiency and its ability to identify patients with advanced neoplastic lesions (ANLs). Data collected from patients referred with biochemically proven iron deficiency (ferritin ≤ 15 µg/L) and synchronous qFIT who underwent full gastrointestinal investigation within NHS Greater Glasgow and Clyde was analysed retrospectively. Patients who did not undergo full investigation, defined as gastroscopy and colonoscopy or CT colonography, were excluded. ANLs were defined as defined as upper GI cancer, colorectal adenoma ≥ 1 cm or colorectal cancer. Area under the curve (AUC) analysis was performed on qFIT results and outcome, defined as the presence of an ANL. AUC analysis guided cut-off scores for qFIT. Patients with a qFIT of <10, 10-200, >200, were allocated a score of 1, 2, and 3, respectively. A total of 575 patients met criteria for inclusion into the study. Overall, qFIT results strongly predicted the presence of ANLs (AUC 0.87, CI 0.81-0.92; P < 0.001). The prevalence of ANLs in patients with scores 1-3 was 1.2, 13.5, and 38.9% respectfully. When controlled for other significant variables, patients with a higher qFIT score were statistically more likely to have an ANL (qFIT score = 2; OR 12.8; P < 0.001, qFIT score = 3, OR 50.0; P < 0.001). A negative qFIT had a high NPV for the presence of ANLs (98.8%, CI 97.0-99.5%). These results strongly suggest that qFIT has validity as a prioritisation tool in patients with iron deficiency; both allowing for a more informed decision of investigation of patients with very low risk of malignancy, and in identifying higher risk patients who may benefit from more urgent endoscopy.

Effect of Hepatocellular Carcinoma Surveillance Programmes on Overall Survival in a Mixed Cirrhotic UK Population: A Prospective, Longitudinal Cohort Study.

INTRODUCTION: Surveillance for hepatocellular carcinoma (HCC) is recommended by national and international guidelines. However, there are no trial data on whether surveillance improves clinical outcomes in a UK cirrhosis population of mixed aetiology. Our aim was to determine the impact of, and adherence to, surveillance on overall survival. METHODS: We prospectively collected data on consecutive patients diagnosed with HCC between January 2009 and December 2015 at two large UK centres. We assessed outcomes depending on whether they had been entered into an HCC surveillance programme, and if they had adhered to that. RESULTS: Out of 985 patients diagnosed with HCC in this study, 40.0% had been enrolled in a surveillance programme. Of these, 76.6% were adherent with surveillance and 24.4% were not. Adherence to surveillance was significantly associated with improved overall survival, even when accounting for lead-time bias using different approaches (HR for 270 days lead-time adjustment 0.64, 0.53 to 0.76, p < 0.001). CONCLUSIONS: When adjusted for lead-time bias, HCC surveillance is associated with improved overall survival; however, the beneficial effect of surveillance on survival was lower than reported in studies that did not account fully for lead-time bias.

Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

1: ESGE recommends in patients with acute upper gastrointestinal hemorrhage (UGIH) the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Patients with GBS ≤ 1 are at very low risk of rebleeding, mortality within 30 days, or needing hospital-based intervention and can be safely managed as outpatients with outpatient endoscopy.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in patients with acute UGIH who are taking low-dose aspirin as monotherapy for secondary cardiovascular prophylaxis, aspirin should not be interrupted. If for any reason it is interrupted, aspirin should be re-started as soon as possible, preferably within 3-5 days.Strong recommendation, moderate quality evidence. 3: ESGE recommends that following hemodynamic resuscitation, early (≤ 24 hours) upper gastrointestinal (GI) endoscopy should be performed. Strong recommendation, high quality evidence. 4: ESGE does not recommend urgent (≤ 12 hours) upper GI endoscopy since as compared to early endoscopy, patient outcomes are not improved. Strong recommendation, high quality evidence. 5: ESGE recommends for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. 6: ESGE recommends for patients with an ulcer with a nonbleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy, or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, high quality evidence. 7 : ESGE suggests that in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic spray/powder or cap-mounted clip should be considered. Weak recommendation, low quality evidence. 8: ESGE recommends that for patients with clinical evidence of recurrent peptic ulcer hemorrhage, use of a cap-mounted clip should be considered. In the case of failure of this second attempt at endoscopic hemostasis, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after failed TAE. Strong recommendation, moderate quality evidence. 9: ESGE recommends high dose proton pump inhibitor (PPI) therapy for patients who receive endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endoscopically. (A): PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g., 80 mg then 8 mg/hour) for 72 hours post endoscopy. (B): High dose PPI therapies given as intravenous bolus dosing (twice-daily) or in oral formulation (twice-daily) can be considered as alternative regimens.Strong recommendation, high quality evidence. 10: ESGE recommends that in patients who require ongoing anticoagulation therapy following acute NVUGIH (e. g., peptic ulcer hemorrhage), anticoagulation should be resumed as soon as the bleeding has been controlled, preferably within or soon after 7 days of the bleeding event, based on thromboembolic risk. The rapid onset of action of direct oral anticoagulants (DOACS), as compared to vitamin K antagonists (VKAs), must be considered in this context.Strong recommendation, low quality evidence.

ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study.

OBJECTIVES: Existing scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB. DESIGN AND SETTING: International cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score's performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk. PARTICIPANTS AND RESULTS: We included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81-84) than existing scores (AUROCs: 0.65-0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4-7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; p<0.001). In LGIB, patients with low, medium and high ABC scores had in-hospital mortality rates of 0.6%, 6.3% and 18%, respectively. CONCLUSIONS: In contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.