Abstract

INTRODUCTION Acute variceal haemorrhage (AVH) in patients with cirrhosis remains a topic of great interest. Although several guidelines recommend endoscopy within 24 hours after AVH, there is no consensus on the most appropriate time to perform this intervention. The purpose of this study is to identify whether urgent endoscopy (within 6 hours after gastroenterological consultation) is superior to non-urgent endoscopy (between 6 hours and 24 hours after gastroenterological consultation) in reducing the rebleeding rate of these patients. METHODS AND ANALYSIS This is a single-centred, prospective, randomised clinical trial. Between March 2021 and December 2023, an estimated 400 patients will be randomised in a 1:1 ratio to receive endoscopic intervention either within 6 hours or between 6 and 24 hours after gastroenterological consultation. Randomisation will be conducted by permuted block randomisation, with stratification by age, systolic blood pressure and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of AVH. The secondary efficacy endpoints mainly include all-cause mortality within 42 days after randomisation, persistent bleeding, length of hospitalisation, etc. ETHICS AND DISSEMINATION The study protocol was approved by the Ethical Committees of Jinling Hospital (authorised ethics no. DZQH-KYLL-21-01). This trial will provide valuable insights into the timing of endoscopic intervention for AVH in patients with cirrhosis. Furthermore, the trial results and conclusions could provide high-quality evidence to guide clinical research and treatment. TRIAL REGISTRATION NUMBER NCT04786743.

Abstract

The optimal treatment for gastric varices (GVs) has not yet been fully determined. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis. Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). The primary outcomes were gastric variceal rebleeding or all-cause rebleeding. The patient characteristics were well-balanced between two groups. The mean follow-up time was 27.1 ± 12 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. The probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (p = 0.024). The probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection vs BRTO was 77% vs 96.3% and 65.2% vs 92.6% (p = 0.004). The survival rates, frequency of complications, and worsening of EVs were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs. CONCLUSIONS BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.

Abstract

BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children and adolescents with chronic liver disease or portal vein thrombosis. Prevention is, therefore, important. Randomised clinical trials have shown that non-selective beta-blockers and endoscopic variceal band ligation decrease the incidence of variceal bleeding in adults. In children and adolescents, band ligation, beta-blockers, and sclerotherapy have been proposed as primary prophylaxis alternatives for oesophageal variceal bleeding. However, it is unknown whether these interventions are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES To assess the benefits and harms of band ligation compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, and two other databases (April 2020). We scrutinised the reference lists of the retrieved publications, and we also handsearched abstract books of the two main paediatric gastroenterology and hepatology conferences from January 2008 to December 2019. We also searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA We aimed to include randomised clinical trials irrespective of blinding, language, or publication status, to assess the benefits and harms of band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. If the search for randomised clinical trials retrieved quasi-randomised and other observational studies, then we read them through to extract information on harm. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology to perform this systematic review. We used GRADE to assess the certainty of evidence for each outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We used the intention-to-treat principle. We analysed data using Review Manager 5. MAIN RESULTS One conference abstract, describing a feasibility multi-centre randomised clinical trial, fulfilled our review inclusion criteria. We judged the trial at overall high risk of bias. This trial was conducted in three hospital centres in the United Kingdom. The aim of the trial was to determine the feasibility and safety of further larger randomised clinical trials of prophylactic band ligation versus no active treatment in children with portal hypertension and large oesophageal varices. Twelve children received prophylactic band ligation and 10 children received no active treatment. There was no information on the age of the children included, or about the diagnosis of any child included. All children were followed up for at least six months. Mortality was 8% (1/12) in the band ligation group versus 0% (0/10) in the no active intervention group (risk ratio (RR) 2.54, 95% confidence interval (CI) 0.11 to 56.25; very low certainty of evidence). The abstract did not report when the death occurred, but we assume it happened between the six-month follow-up and one year. No child (0%) in the band ligation group developed adverse events (RR 0.28, 95% CI 0.01 to 6.25; very low certainty of evidence) but one child out of 10 (10%) in the no active intervention group developed idiopathic thrombocytopaenic purpura. One child out of 12 (8%) in the band ligation group underwent liver transplantation versus none in the no active intervention group (0%) (RR 2.54, 95% CI 0.11 to 56.25; very low certainty of evidence). The trial reported no other serious adverse events or liver-related morbidity. Quality of life was not reported. Oesophageal variceal bleeding occurred in 8% (1/12) of the children in the band ligation group versus 30% (3/10) of the children in the no active intervention group (RR 0.28, 95% CI 0.03 to 2.27; very low certainty of evidence). No adverse events considered non-serious were reported. Two children were lost to follow-up by one-year. Ten children in total completed the trial at two-year follow-up. There was no information on funding. We found two observational studies on endoscopic variceal ligation when searching for randomised trials. One found no harm, and the other reported E nterobacter cloacae septicaemia in one child and mild, transient, upper oesophageal sphincter stenosis in another. We did not assess these studies for risk of bias. We did not find any ongoing randomised clinical trials of interest to our review. AUTHORS' CONCLUSIONS The evidence, obtained from only one feasibility randomised clinical trial at high risk of bias, is very scanty. It is very uncertain about whether prophylactic band ligation versus sham or no (active) intervention may affect mortality, serious adverse events and liver-related morbidity, or oesophageal variceal bleeding in children and adolescents with portal hypertension and large oesophageal varices. We have no data on quality of life. No adverse events considered non-serious were reported. The results presented in the trial need to be interpreted with caution. In addition, the highly limited data cover only part of our research question; namely, children with portal hypertension and large oesophageal varices. Data on children with portal vein thrombosis are lacking. Larger randomised clinical trials assessing the benefits and harms of band ligation compared with sham treatment for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, quality of life, failure to control bleeding, and adverse events.

Abstract

BACKGROUND Approximately 40% to 95% of people with liver cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed within about one to three years after diagnosis. Several different treatments are available, including, among others, endoscopic sclerotherapy, variceal band ligation, somatostatin analogues, vasopressin analogues, and balloon tamponade. However, there is uncertainty surrounding the individual and relative benefits and harms of these treatments. OBJECTIVES To compare the benefits and harms of different initial treatments for variceal bleeding from oesophageal varices in adults with decompensated liver cirrhosis, through a network meta-analysis; and to generate rankings of the different treatments for acute bleeding oesophageal varices, according to their benefits and harms. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until 17 December 2019, to identify randomised clinical trials (RCTs) in people with cirrhosis and acute bleeding from oesophageal varices. SELECTION CRITERIA We included only RCTs (irrespective of language, blinding, or status) in adults with cirrhosis and acutely bleeding oesophageal varices. We excluded RCTs in which participants had bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those in whom initial haemostasis was achieved before inclusion into the trial, and those who had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS software, using Bayesian methods, and calculated the differences in treatments using odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We performed also the direct comparisons from RCTs using the same codes and the same technical details. MAIN RESULTS We included a total of 52 RCTs (4580 participants) in the review. Forty-eight trials (4042 participants) were included in one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those with and without a previous history of bleeding. We included outcomes assessed up to six weeks. All trials were at high risk of bias. A total of 19 interventions were compared in the trials (sclerotherapy, somatostatin analogues, vasopressin analogues, sclerotherapy plus somatostatin analogues, variceal band ligation, balloon tamponade, somatostatin analogues plus variceal band ligation, nitrates plus vasopressin analogues, no active intervention, sclerotherapy plus variceal band ligation, balloon tamponade plus sclerotherapy, balloon tamponade plus somatostatin analogues, balloon tamponade plus vasopressin analogues, variceal band ligation plus vasopressin analogues, balloon tamponade plus nitrates plus vasopressin analogues, balloon tamponade plus variceal band ligation, portocaval shunt, sclerotherapy plus transjugular intrahepatic portosystemic shunt (TIPS), and sclerotherapy plus vasopressin analogues). We have reported the effect estimates for the primary and secondary outcomes when there was evidence of differences between the interventions against the reference treatment of sclerotherapy, but reported the other results of the primary and secondary outcomes versus the reference treatment of sclerotherapy without the effect estimates when there was no evidence of differences in order to provide a concise summary of the results. Overall, 15.8% of the trial participants who received the reference treatment of sclerotherapy (chosen because this was the commonest treatment compared in the trials) died during the follow-up periods, which ranged from three days to six weeks. Based on moderate-certainty evidence, somatostatin analogues alone had higher mortality than sclerotherapy (OR 1.57, 95% CrI 1.04 to 2.41; network estimate; direct comparison: 4 trials; 353 participants) and vasopressin analogues alone had higher mortality than sclerotherapy (OR 1.70, 95% CrI 1.13 to 2.62; network estimate; direct comparison: 2 trials; 438 participants). None of the trials reported health-related quality of life. Based on low-certainty evidence, a higher proportion of people receiving balloon tamponade plus sclerotherapy had more serious adverse events than those receiving only sclerotherapy (OR 4.23, 95% CrI 1.22 to 17.80; direct estimate; 1 RCT; 60 participants). Based on moderate-certainty evidence, people receiving vasopressin analogues alone and those receiving variceal band ligation had fewer adverse events than those receiving only sclerotherapy (rate ratio 0.59, 95% CrI 0.35 to 0.96; network estimate; direct comparison: 1 RCT; 219 participants; and rate ratio 0.40, 95% CrI 0.21 to 0.74; network estimate; direct comparison: 1 RCT; 77 participants; respectively). Based on low-certainty evidence, the proportion of people who developed symptomatic rebleed was smaller in people who received sclerotherapy plus somatostatin analogues than those receiving only sclerotherapy (OR 0.21, 95% CrI 0.03 to 0.94; direct estimate; 1 RCT; 105 participants). The evidence suggests considerable uncertainty about the effect of the interventions in the remaining comparisons where sclerotherapy was the control intervention. AUTHORS' CONCLUSIONS Based on moderate-certainty evidence, somatostatin analogues alone and vasopressin analogues alone (with supportive therapy) probably result in increased mortality, compared to endoscopic sclerotherapy. Based on moderate-certainty evidence, vasopressin analogues alone and band ligation alone probably result in fewer adverse events compared to endoscopic sclerotherapy. Based on low-certainty evidence, balloon tamponade plus sclerotherapy may result in large increases in serious adverse events compared to sclerotherapy. Based on low-certainty evidence, sclerotherapy plus somatostatin analogues may result in large decreases in symptomatic rebleed compared to sclerotherapy. In the remaining comparisons, the evidence indicates considerable uncertainty about the effects of the interventions, compared to sclerotherapy.

Abstract

AIM: Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient's quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. METHODS Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child-Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. RESULTS There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child-Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = -3.44, 95% CI: -7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: -723.21 to 205.57, p=0.24; 1 year: MD = -320.12, 95% CI: -438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = -0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = -1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. CONCLUSIONS Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.

Abstract

Background and aim Guidelines recommend use of ligation and vasoactive drugs as first-line therapy and as grade A evidence for acute variceal bleeding (AVB), although Western studies about this issue are lacking. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of endoscopic treatments for AVB in patients with cirrhosis. Trials that included patients with hepatocellular carcinoma, use of portocaval shunts or esophageal resection, balloon tamponade as first bleeding control measure, or that received placebo or elective treatment in one study arm were excluded. Results A total of 8382 publications were searched, of which 36 RCTs with 3593 patients were included. Ligation was associated with a significant improvement in bleeding control (relative risk [RR] 1.08; 95 % confidence interval [CI] 1.02 - 1.15) when compared to sclerotherapy. Sclerotherapy combined with vasoactive drugs showed higher efficacy in active bleeding control compared to sclerotherapy alone (RR 1.17; 95 % CI 1.10 - 1.25). The combination of ligation and vasoactive drugs was not superior to ligation alone in terms of overall rebleeding (RR 2.21; 95 %CI 0.55 - 8.92) and in-hospital mortality (RR 1.97; 95 %CI 0.78 - 4.97). Other treatments did not generate meta-analysis. Conclusions This study showed that ligation is superior to sclerotherapy, although with moderate heterogeneity. The combination of sclerotherapy and vasoactive drugs was more effective than sclerotherapy alone. Although current guidelines recommend combined use of ligation with vasoactive drugs in treatment of esophageal variceal bleeding, this study failed to demonstrate the superiority of this combined treatment.

Abstract

Background Though endoscopic variceal ligation (EVL) is commonly being used and has overcome the disadvantages of sclerotherapy (ST), still sclerotherapy is used as a therapeutic procedure for bleeding esophageal varices in the present institute. Hence, the study was done to see the advantages of EVL over ST. Methods Patients with portal hypertension and bleeding esophageal varices underwent banding if found to have grade 3 or 4 varices. They were randomized to EVL group, where they were reviewed after two weeks for any residual varices for which repeat banding was done and endoscopic sclerotherapy (EST) group, where ST was done until the varices were obliterated or reduced to grade 1. The efficacy, complications, recurrent bleeding rate and recurrence of varices were compared. Results A total of 60 patients were included, 30 in each group. In EVL group, four sessions were needed to eradicate the varices in 73% of patients while it was five sessions in EST group (46% patients) (p-value = 0.0001). The mean number of sessions needed in EVL and EST group was 3.73 and 5.36, respectively. The average time taken for eradication of varices was 78.6 and 134.6 days in EVL and EST group, respectively (p-value = 0.004). Complications were higher in EST group (p-value < 0.05). Conclusion EVL alone was effective than ST in terms of the number of sessions needed for eradication of varices and total duration required to completely obliterate them. The complications were less in EVL group with no significant difference in recurrent bleeding rate and recurrence of varices between the groups.

Abstract

BACKGROUND Variceal haemorrhage that is refractory or recurs after pharmacologic and endoscopic therapy requires a portal decompression shunt (either surgical shunts or radiologic shunt, transjugular intrahepatic portosystemic shunt (TIPS)). TIPS has become the shunt of choice; however, is it the preferred option? This review assesses evidence for the comparisons of surgical portosystemic shunts versus TIPS for variceal haemorrhage in people with cirrhotic portal hypertension. OBJECTIVES To assess the benefits and harms of surgical portosystemic shunts versus transjugular intrahepatic portosystemic shunt (TIPS) for treatment of refractory or recurrent variceal haemorrhage in people with cirrhotic portal hypertension. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched on-line trial registries, reference lists of relevant articles, and proceedings of relevant associations for trials that met the inclusion criteria for this review (date of search 8 March 2018). SELECTION CRITERIA Randomised clinical trials comparing surgical portosystemic shunts versus TIPS for the treatment of refractory or recurrent variceal haemorrhage in people with cirrhotic portal hypertension. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials and extracted data using methodological standards expected by Cochrane. We assessed risk of bias according to domains and risk of random errors with Trial Sequential Analysis (TSA). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS We found four randomised clinical trials including 496 adult participants diagnosed with variceal haemorrhage due to cirrhotic portal hypertension. The overall risk of bias in all the trials was judged at high risk. All the trials were conducted in the United States of America (USA). Two of the trials randomised participants to selective surgical shunts versus TIPS. The other two trials randomised participants to non-selective surgical shunts versus TIPS. The diagnosis of liver cirrhosis was by clinical and laboratory findings. We are uncertain whether there is a difference in all-cause mortality at 30 days between surgical portosystemic shunts compared with TIPS (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.44 to 1.99; participants = 496; studies = 4). We are uncertain whether there is a difference in encephalopathy between surgical shunts compared with TIPS (RR 0.56, 95% CI 0.27 to 1.16; participants = 496; studies = 4). We found evidence suggesting an increase in the occurrence of the following harms in the TIPS group compared with surgical shunts: all-cause mortality at five years (RR 0.61, 95% CI 0.42 to 0.90; participants = 496; studies = 4); variceal rebleeding (RR 0.18, 95% CI 0.07 to 0.49; participants = 496; studies = 4); reinterventions (RR 0.13, 95% CI 0.06 to 0.28; participants = 496; studies = 4); and shunt occlusion (RR 0.14, 95% CI 0.04 to 0.51; participants = 496; studies = 4). We could not perform an analysis of health-related quality of life but available evidence appear to suggest improved health-related quality of life in people who received surgical shunt compared with TIPS. We downgraded the certainty of the evidence for all-cause mortality at 30 days and five years, irreversible shunt occlusion, and encephalopathy to very low because of high risk of bias (due to lack of blinding); inconsistency (due to heterogeneity); imprecision (due to small sample sizes of the individual trials and few events); and publication bias (few trials reporting outcomes). We downgraded the certainty of the evidence for variceal rebleeding and reintervention to very low because of high risk of bias (due to lack of blinding); imprecision (due to small sample sizes of the individual trials and few events); and publication bias (few trials reporting outcomes). The small sample sizes and few events did not allow us to produce meaningfu

Abstract

AIM: Portal hypertension is a common complication of chronic liver disease and can cause variceal bleeding which is associated with high mortality. Choices for the treatment of variceal bleeding include surgical shunts and endoscopic sclerotherapy. The aim of this study was to compare the efficacy of surgical shunts and endoscopic sclerotherapy in treating variceal bleeding due to portal hypertension. DESIGN Systematic review and meta-analysis. SETTING Medline, PubMed, Cochrane and Google Scholar databases were searched until 12 February 2015, for relevant randomised control trials. Twenty studies with a total of 1540 participants were included. PATIENTS Patients with variceal bleeding due to portal hypertension. INTERVENTIONS Surgical shunts compared to endoscopic sclerotherapy. MAIN OUTCOME MEASURES Rates of rebleeding, survival and hepatoencephalopathy, and length of hospital stay. RESULTS Pooled data for 17 studies showed that the rate of rebleeding was significantly more frequent with sclerotherapy compared with surgical shunt therapy (OR 3.99, 95% CI 2.98 to 5.33, p<0.001). The sclerotherapy patient group compared with the shunt group was less likely to develop hepatoencephalopathy (15 studies: pooled OR 0.53, 95% CI 0.31 to 0.91, p=0.021) and had shorter hospital stays (pooled mean difference -4.32, 95% CI -7.97 to -0.66, p=0.021). No significant difference in the survival rate was observed between the two groups (seven studies: OR 1.01, 95% CI 0.63 to 1.62, p=0.964). CONCLUSION This analysis indicated that the two types of treatment have similar mortality rates but differed with respect to rebleeding rate, incidence of hepatoencephalopathy and length of hospital stay.

Abstract

BACKGROUND AND AIMS Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. METHODS The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. RESULTS Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. CONCLUSIONS Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.