Non-selective beta blocker (NSBB) is the preferred treatment option for primary prophylaxis of high-risk oesophageal varices, and endoscopic band ligation (EBL) is reserved for those intolerant to NSBB. In this meta-analysis, we aim to compare the outcomes of NSBB, EBL and combined therapy for primary prophylaxis of high-risk oesophageal varices.

Major databases, such as MedLine, Embase and Cochrane Library were searched in October 2024 to identify studies comparing clinical outcomes between combined approaches versus NSBB versus EBL only. Only randomised trials were included. Meta-analysis was performed using the random-effects model, and heterogeneity was assessed by I2% statistics.

Six randomised trials were included, which consisted of 1011 participants (NSBB 302, EBL 300 and 409 combined) (75.27% males), with an average age of 51.06 years. The NSBBs used were propranolol, nadolol and carvedilol, with an average follow-up of 17.54 months. The combined approach significantly reduced the first episode of variceal bleeding compared to NSBB alone (pooled RR 0.39 [95% CI 0.19-0.76], p = 0.009) and EBL alone (RR 0.46, 0.29-0.74; p = 0.002). The pooled rate of bleeding with the combined approach was 9.4% [95% CI 6%-14.3%], with NSBB being 28.2% [95% CI 12.9%-51%] and with EBL being 13.9% [6%-17%]. Pooled ratios for bleeding-related mortality were significantly better with the combined approach when compared to NSBB alone.

Primary prophylaxis of high-grade varices by combined therapy demonstrated a significantly lower risk of variceal bleeding than NSBB or EBL alone. We recommend these findings be incorporated into forthcoming guidelines.

Portal hypertension (PH), a common complication of liver cirrhosis, results in development of esophageal varices. When esophageal varices rupture, they cause significant upper gastrointestinal bleeding with mortality rates up to 20% despite state-of-the-art treatment. Thus, prophylactic measures are of utmost importance to improve outcomes of patients with PH. Several high-quality studies have demonstrated that non-selective beta blockers (NSBBs) or endoscopic band ligation (EBL) are effective for primary prophylaxis of variceal bleeding. In secondary prophylaxis, a combination of NSBB + EBL should be routinely used. Once esophageal varices develop and variceal bleeding occurs, standardized treatment algorithms should be followed to minimize bleeding-associated mortality. Special attention should be paid to avoidance of overtransfusion, early initiation of vasoconstrictive therapy, prophylactic antibiotics and early endoscopic therapy. Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding, and potentially in Child B patients with active bleeding at endoscopy. The use of carvedilol, safety of NSBBs in advanced cirrhosis (i.e. with refractory ascites) and assessment of hepatic venous pressure gradient response to NSBB is discussed. In the present review, we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.

Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years. There are several different treatments to prevent bleeding, including: beta-blockers, endoscopic sclerotherapy, and variceal band ligation. However, there is uncertainty surrounding their individual and relative benefits and harms.

To compare the benefits and harms of different treatments for prevention of first variceal bleeding from oesophageal varices in adults with liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for prevention of first variceal bleeding from oesophageal varices according to their safety and efficacy.

We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to December 2019 to identify randomised clinical trials in people with cirrhosis and oesophageal varices with no history of bleeding.

We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and oesophageal varices with no history of bleeding. We excluded randomised clinical trials in which participants had previous bleeding from oesophageal varices and those who had previously undergone liver transplantation or previously received prophylactic treatment for oesophageal varices.

We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR), and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute for Health and Care Excellence Decision Support Unit guidance. We performed the direct comparisons from randomised clinical trials using the same codes and the same technical details.

We included 66 randomised clinical trials (6653 participants) in the review. Sixty trials (6212 participants) provided data for one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those at high risk of bleeding from oesophageal varices. The follow-up in the trials that reported outcomes ranged from 6 months to 60 months. All but one of the trials were at high risk of bias. The interventions compared included beta-blockers, no active intervention, variceal band ligation, sclerotherapy, beta-blockers plus variceal band ligation, beta-blockers plus nitrates, nitrates, beta-blockers plus sclerotherapy, and portocaval shunt. Overall, 21.2% of participants who received non-selective beta-blockers ('beta-blockers') - the reference treatment (chosen because this was the most common treatment compared in the trials) - died during 8-month to 60-month follow-up. Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates all had lower mortality versus no active intervention (beta-blockers: HR 0.49, 95% CrI 0.36 to 0.67; direct comparison HR: 0.59, 95% CrI 0.42 to 0.83; 10 trials, 1200 participants; variceal band ligation: HR 0.51, 95% CrI 0.35 to 0.74; direct comparison HR 0.49, 95% CrI 0.12 to 2.14; 3 trials, 355 participants; sclerotherapy: HR 0.66, 95% CrI 0.51 to 0.85; direct comparison HR 0.61, 95% CrI 0.41 to 0.90; 18 trials, 1666 participants; beta-blockers plus nitrates: HR 0.41, 95% CrI 0.20 to 0.85; no direct comparison). No trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation had a higher number of serious adverse events (number of events) than beta-blockers (rate ratio 10.49, 95% CrI 2.83 to 60.64; 1 trial, 168 participants). Based on low-certainty evidence, beta-blockers plus nitrates had a higher number of 'any adverse events (number of participants)' than beta-blockers alone (OR 3.41, 95% CrI 1.11 to 11.28; 1 trial, 57 participants). Based on low-certainty evidence, adverse events (number of events) were higher in sclerotherapy than in beta-blockers (rate ratio 2.49, 95% CrI 1.53 to 4.22; direct comparison rate ratio 2.47, 95% CrI 1.27 to 5.06; 2 trials, 90 participants), and in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison rate ratio 1.72, 95% CrI 1.08 to 2.76; 1 trial, 140 participants). Based on low-certainty evidence, any variceal bleed was lower in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison HR 0.21, 95% CrI 0.04 to 0.71; 1 trial, 173 participants). Based on low-certainty evidence, any variceal bleed was higher in nitrates than beta-blockers (direct comparison HR 6.40, 95% CrI 1.58 to 47.42; 1 trial, 52 participants). The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons.

Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates may decrease mortality compared to no intervention in people with high-risk oesophageal varices in people with cirrhosis and no previous history of bleeding. Based on low-certainty evidence, variceal band ligation may result in a higher number of serious adverse events than beta-blockers. The evidence indicates considerable uncertainty about the effect of beta-blockers versus variceal band ligation on variceal bleeding. The evidence also indicates considerable uncertainty about the effect of the interventions in most of the remaining comparisons.

The recurrence of esophageal varices remains high in patients with hepatic portal hypertension after the endoscopic esophageal variceal eradication therapies, including endoscopic variceal band ligation (EVL), injection sclerotherapy (EIS) or EVL plus EIS. The aim of this study was to evaluate the endoscopic ultrasound probe examinations (EUP) findings in the prediction of recurrence following esophageal variceal eradication in a prospective cohort.

A total of 206 cirrhotic portal hypertension patients with esophageal variceal eradication, who underwent endoscopic variceal therapy (EVL or EIS or EVL plus EIS) were initially enrolled. All patients were scheduled for a follow-up every 6 months for up to 3 years. EUP was performed to evaluate peri-esophageal collateral veins (peri-ECVs), perforating veins (PFV) and para-esophageal collateral veins (para-ECVs). In addition, computed tomography (CT) were conducted to detect portal vein diameter, portal vein embolus, and major portosystemic collateral shunts. The relationship between esophageal variceal recurrence and EUP findings were analyzed.

We found that as high as 93.5% of patients developed esophageal variceal recurrence in the 3-year follow-up. The time of esophageal variceal recurrence after variceal eradication was 13.4 months (13.4 ± 9.2 months). Furthermore, the median time of recurrence in patients who were undertaken EVL,EIS and EVL plus EIS was 10, 13 and 12 months, respectively. We identified that the risk factors, including EVL (OR 0.23, 95% CI 0.08-0.71, p < 0.01), Child-Pugh score (OR 3.32,95% CI 1.31-35.35, p < 0.05), large peri-ECVs (OR 4.56, 95% CI 2.17-9.58, p < 0.0001), and existence of PFV (OR 2.14, 95% CI 1.44-3.16, p < 0.001), were significantly associated with the recurrence of esophageal varices. The peri-ECVs and PFV showed better ability to predict esophageal variceal recurrence. When cut-off value of peri-ECVs diameter was 3.5 mm, the specificity of prediction 1-year variceal recurrence was 86% and the sensitivity was 45%.

The EUP appears to be very effective, convenient and economical examinations to predict esophageal varices recurrence after variceal eradication by endoscopic therapies. The high Child-pugh score, large peri-ECVs, and PFV are independent risk factors related to esophageal varices recurrence.

There are scanty data on the long-term outcome of endoscopic variceal band ligation (EVL) for esophageal varices.

Adult patients suffering from a chronic liver disease (CLD) undergoing EVL of esophageal varices of grade 2 and above between January 2006 and December 2015 were followed up for the recurrence of varices, worsening of portal hypertensive gastropathy (PHG), rebleeding, and mortality. EVL was done as primary prophylaxis of bleeding in 72 and as secondary prophylaxis in 175 patients. All received propranolol after EVL if there was no contraindication.

Two hundred and forty-seven CLD patients (mean age 51.83 ± 11.28 years, 179 males) underwent 306 EVL sessions. The most common etiology was alcohol (53%). Sixty-eight percent of patients had grade 3 esophageal varices 76.5% had PHG. There was no immediate post-EVL bleeding or 30-day mortality. Variceal obliteration was achieved in 100% with 19% recurrence within a mean period of 53.74 ± 27.2 months. PHG worsened in 49.7%. Overall, rebleeding occurred in 13.8%, 4.3% from recurrent varices. There was no difference in variceal recurrence (16.7% vs. 20%) and incidence of rebleeding (9.7% vs. 13.7%) between patients undergoing EVL for primary and secondary prophylaxis. Cumulative rebleeding rates after 1, 5, and 9 years were 1.6%, 9.2%, and 11.4%, respectively. The overall mortality was 85%, mostly from progressive CLD, and only 8.6% was due to rebleeding. On subgroup analysis, the factors significantly associated with rebleeding was Child-Pugh class C and worsened PHG those with mortality were alcohol and Child-Pugh class C.

EVL is effective in the long-term for both primary and secondary prophylaxis of esophageal variceal bleeding.

Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used.

To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding.

(Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP.

Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567).

EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

Chronic radiation proctopathy (CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbid-mortality. Endoscopy has a role in the diagnosis, staging and treatment of this disease. Currently available endoscopic modalities are formalin, potassium titanyl phosphate laser, neodymium:yttrium-aluminum-garnet laser, argon laser, bipolar electrocoagulation (BiCAP), heater probe, band ligation, cryotherapy, radiofrequency ablation and argon plasma coagulation (APC). Among these options, APC is the most promising.

The objective of this work is to assess the use of constant-wavelength synchronous fluorescence spectroscopy (SFS) in comparison to conventional fluorescence spectroscopy (CFS) for the investigation of the supramolecular host-guest interaction of β-CD with propranolol (PPL) in aqueous solutions. Scanning for the optimal Δλ at which the SFS can be performed in the presence of β-CD was examined. The results obtained revealed three distinguishable shapes for PPL using SFS that can be represented by three different Δλ values, namely 10, 40, and 100 nm. However, the effect of the β-CD concentration on the fluorescence intensity of PPL was examined using CFS and SFS of PPL at a Δλ of 10 and 100 nm. The change in the fluorescence intensity was used to calculate the equilibrium constant (Keq) for the formation of the β-CD:PPL inclusion complex by applying the Benesi-Hildebrand method. Keq values of 108, 112, and 117 M(-1) were obtained using SFS with a Δλ of 10 and 100 nm, and CFS, respectively. Further, the SFS method was successfully employed to examine the iodide quenching effect on the fluorescence intensity of PPL, where the results obtained revealed a Stern-Volmer quenching constant of 42.8 M(-1), which is in good agreement with results obtained using CFS. All results obtained using the SFS method were compared with the results obtained using the CFS method.