Vonoprozan: potentially new first-line treatment for delayed upper gastrointestinal bleeds following endoscopic procedures? A letter to the editor

Endoscopy nowadays is widely used as a diagnostic and therapeutic tool for various gastrointestinal diseases due to it being less invasive and safer. However, amongst some adverse events is delayed bleeding. The definition of delayed bleeding requires endoscopic hemostasis and/or blood transfusion after at least two days of treatment. (1) Oesophageal cancer is comparatively more common in Pakistan, being 7th most common malignancy in men and 6th most common in women in Karachi. (2) Oesophageal endoscopic submucosal dissection (E-ESD) employed in the treatment of the above- mentioned cancer has an incidence of delayed bleeding of about 1.3-6.7%. (1) The prevalence of gastric cancer across Pakistan was about 2-18% (3), for which endoscopic submucosal dissection is often used has an incidence of delayed bleeding of 4.7-15.6%. (1) Endoscopic therapy for gastroesophageal varices can also result in delayed bleeding, the incidence of which easily reaches up to 10%. (1) In a retrospective cohort study of 124,422 patients conducted in Japan, it was found that vonoprazan was more effective in reducing the risk of delayed bleeding compared to omeprazole. (OR= 0.75) (1) Vonoprazan works by competitively inhibiting the potassium-acid channel resulting in strong and sustained acid inhibition. (4) It was also found to have a superior effect in the eradication of H Pylori and an equal effect in acid-related disorders. (5) In the retrospective study mentioned above, it is also worth noting that the efficacy of vonoprazan was variable with respect to procedures and was most prominent with gastroduodenal endoscopic submucosal dissection (OR=0.70). (1) Other procedures did not elicit any significant difference. In addition, standard/high dose vonoprazan proved to be most efficacious in reducing the risk of delayed bleeding compared with standard/high-dose PPI and low-dose vonoprazan. It was also observed that patients taking anti-thrombotic medications at a higher risk of delayed bleeding also benefited from high-dose vonoprazan. (OR=0.74) (1) The findings above compel the conclusion that high dose vonoprazan should be ideal for reducing the risk of delayed bleeding in patients who have undergone gastroduodenal endoscopic submucosal dissection and/or are on anti-thrombotics. Though high-dose vonoprazan does look promising, it is imperative that more randomized controlled trials on more diverse populations be conducted to further explore its efficacy and safety as the drug might be a potential first line of therapy.

Risk Factors for Esophageal Collateral Veins in Cirrhosis with and without Previous Endoscopic Esophageal Variceal Therapy

Background. Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear. Methods. We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). Results. Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250, p = 0.026), previous EVL (OR = 1.929, p = 0.044), platelet (OR = 0.993, p = 0.008), and esophageal varices needing treatment (EVNTs) (OR = 2.422, p = 0.006). The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers (OR = 0.294, p = 0.042) and EVNTs (OR = 3.714, p = 0.006) in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively. Conclusions. The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL.

Association of ABO Blood Type with Bleeding Severity in Patients with Acute Gastroesophageal Variceal Bleeding

Background and Objectives: ABO blood types have been implicated as potential risk factors for various hemorrhagic diseases. No study has investigated the association between gastroesophageal variceal bleeding and ABO blood types. We aimed to evaluate the impact of ABO blood types on mortality and bleeding risk in acute gastroesophageal variceal bleeding. Materials and Methods: This is a retrospective observational study. Patients presenting with acute gastroesophageal varices bleeding diagnosed by endoscopy were enrolled, and were divided by blood type into a type O group and non-type O group. The outcomes were death within 30 days and the proportion of further bleeding. We used generalized linear mixed-effects models to analyze the outcomes. Results: A total of 327 patients and 648 records of emergency room visits were included. The 30-day mortality was 14.8% (21 of 142 patients) in the type O group, and 16.2% (30 of 185 patients) in the non-type O group (p = 0.532). Further bleeding within 30 days occurred in 34 cases (12.6%) in the type O group, and in 26 cases (6.9%) in the non-type O group (p = 0.539). Conclusions: There was no significant difference in blood transfusion volume in 24 h, recurrent bleeding rates, or mortality between patients with blood type O and those with non-type O.

Additional Benefits Conferred by Endoscopic Sclerotherapy to Liver Cirrhosis Patients Receiving Endoscopic Variceal Ligation

Objective. Gastroesophageal varices are a direct consequence of portal hypertension in cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in reduced mortality and morbidity rates. The study was aimed to analyze the short-term and long-term efficacy of different endoscopic methods in the treatment of gastric varices in cirrhotic patients. Methods. From January 2016 to December 2019, 135 patients with liver cirrhosis and gastric varices undergoing different endoscopic treatment protocols were retrospectively analyzed. The patients were divided into three groups according to endoscopic variceal ligation, endoscopic sclerotherapy, and a combination of both, respectively. Main outcomes including the overall response rate, hemostasis, short- and long-term rebleeding (3 months before and after treatment), complication, blood pressure, heart rate, portal venous pressure (PVP), portal vein diameter (PVD), portal vein velocity (PVV), portal vein blood flow (PVF) detected by ultrasound, recurrence rate, and mortality were analyzed after treatments. Results. The overall response rate in the combined group was higher than that in the ligation group and the sclerotherapy group ( P < 0.05 ). The incidence rate of complications in the combined group and the ligation group was lower than that in the sclerotherapy group ( P < 0.05 ). After treatment, the PVP, PVD, and PVF were reduced in the combined group compared with the ligation group and the sclerotherapy group, while the PVV was not ( P < 0.05 ). Lower rates of long-term rebleeding, recurrence, and mortality were noted in the combined group compared to the ligation group and the sclerotherapy group ( P < 0.05 ). Conclusion. Endoscopic variceal ligation combined with endoscopic sclerotherapy is more effective than both alone in treating liver cirrhosis and gastric varices. The combined therapy contributed to reduced short-term and long-term rebleeding rate, decreased long-term recurrence rate, and mortality.

Platelet count and abdominal dynamic CT are useful in predicting and screening for gastroesophageal varices after Fontan surgery

Objective Patients who undergo Fontan surgery for complex cardiac anomalies are prone to developing liver and gastrointestinal complications. In particular, gastroesophageal varices (GEVs) can occur, but their prevalence is unknown. We aimed to elucidate the occurrence of GEVs and the predicting parameters of GEVs in these patients. Materials and methods Twenty-seven patients (median age, 14.8 years; median time since surgery, 12.9 years) who had undergone the Fontan surgery and were examined by abdominal dynamic computed tomography (CT) for the routine follow-up were included in the study. Radiological findings including GEVs and extraintestinal complications were retrospectively evaluated by experienced radiologists in a blinded manner. Relationships between blood-biochemical and demographic parameters and the presence of GEVs were statistically analyzed. Results Dynamic CT revealed gastric varices (n = 3, 11.1%), esophageal varices (n = 1, 3.7%), and gastrorenal shunts (n = 5, 18.5%). All patients with gastric varices had gastrorenal shunts. All gastric varices were endoscopically confirmed as being isolated and enlarged, with indications for preventive interventional therapy. A platelet count lower than 119 × 109 /L was identified as a predictor of GEV (area under the receiver operating curve, 0.946; sensitivity, 100%; and specificity, 87%). Conclusions GEVs are important complications that should not be ignored in patients who have undergone a Fontan procedure. Platelet counts lower than 119 × 109 /L may help to prompt patient screening by using abdominal dynamic CT to identify GEVs and their draining collateral veins in these patients.

Primary Prophylaxis of Variceal Haemorrhage in Patients with Cirrhosis: An Integrated Pharmacological and Endoscopic Approach.

Background: At the present time, in patients with liver cirrhosis and gastroesophageal varices, primary prophylaxis of variceal bleeding made with combination therapy with non-selective b-blockers (NSBBs) and endoscopic band ligation (EBL) is not recommended. The aim of this study was to evaluate if patients who develop an increased bleeding risk from varices while on NSBBs regimen benefit, in terms of bleeding and survival, from adding treatment with EBL. Methods: Patients with endoscopic finding of gastroesophageal varices with increased risk of bleeding (increased variceal size and/or development of red signs) during primary prophylaxis with NSBBs, followed at the Unit of Internal Medicine and Hepatology, University and General Hospital of Padova, Italy, from 2012 to 2019, were retrospectively evaluated. When an increased bleeding risk of the varices was confirmed, patients maintained the pharmacological therapy alone or underwent also EBL. The primary endpoint of the study was the rate of variceal bleeding, the secondary endpoint was mortality at 30 months. Results: Compared to patients treated only with NSBBs (n=56), in patients treated also with EBL (n=45), the 30‐month probability of variceal bleeding (29.1% vs 5.1%; P =0.036) was significantly reduced, while the probability of survival was similar (59.6% vs. 65.7%; P=0.61). On multivariate analysis, treatment with EBL was found to be a weak protective factor for mortality (HR 0.47, P=0.044). Conclusion: In patients with liver cirrhosis, when varices show endoscopic feature of increased haemorrhagic risk, adding EBL to NSBBs is effective in reducing the probability of first bleeding.