Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.

BACKGROUND & AIMS: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

Role of oral iron supplementation for anemia secondary to acute nonvariceal upper gastrointestinal bleeding: a randomized controlled trial.

BACKGROUND AND AIM: Although acute upper gastrointestinal bleeding (UGIB) can lead to anemia, evidence regarding the effects of oral iron supplementation on UGIB-induced anemia following discharge remains lacking. The present study aimed to investigate the effects of oral iron supplementation on hemoglobin response and iron storage in patients with anemia secondary to nonvariceal UGIB. METHODS: This randomized controlled trial included 151 patients with nonvariceal UGIB who had anemia at discharge. Patients were assigned to a 1:1 block in which they were either administered 6 weeks of 600 mg/d oral ferrous fumarate (treatment group, n = 77) or treated without iron supplementation (control group, n = 74). The primary outcome was composite hemoglobin response (hemoglobin elevation greater than 2 g/dL or no anemia at the end of treatment [EOT]). RESULTS: The proportion of patients achieving composite hemoglobin response was greater in the treatment group than in the control group (72.7% vs 45.9%; adjusted risk ratio [RR], 2.980; P = 0.004). At EOT, the percentage change in the hemoglobin level (34.2 ± 24.8% vs 19.4 ± 19.9%; adjusted coefficient, 11.543; P < 0.001) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 µg/L and a transferrin saturation <16% were lower in the treatment group (all P < 0.05). No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups. CONCLUSION: Oral iron supplementation exerts beneficial effects on anemia and iron storage following nonvariceal UGIB without significantly impacting rates of adverse effects or adherence.

Diagnostic power of DNA methylation markers suggestive of cholangiocarcinoma in ERCP-based brush cytology.

BACKGROUND AND AIMS: Accurate differentiation between cholangiocarcinoma (CCA) and benign biliary stricture is of paramount importance. Biliary brush cytology is a simple and safe diagnostic approach that provides relatively high specificity; however, sensitivity is limited. Previous reports indicated the aberrations of DNA methylation in CCA. This study aimed to investigate the diagnostic performance of the methylation index (MI) of HOXA1 and NEUROG1 gene promoters in CCA. METHODS: Patients with biliary stricture who underwent ERCP with brush cytology in Siriraj Hospital from September 2016 to December 2019 were prospectively enrolled. The MI of HOXA1 (MI_H) and MI of NEUROG1 (MI_N) were determined by quantitative methylation-specific polymerase chain reaction. The diagnostic power for CCA was tested for MI from both genes and serum carbohydrate antigen 19-9 (CA19-9). RESULTS: Sixty-seven patients were included in the study; 41 patients had a final diagnosis of CCA, and 26 patients were determined to have a benign biliary stricture. The results showed that both MI_H and MI_N had higher sensitivity and accuracy (95.1% and 82.3% and 90.2% and 89.5%, respectively) than brush cytology (61.5% and 78.1%) and CA19-9 (69.4% and 77.8%). The combination of brush cytology, both methylation markers, and CA19-9 increased the sensitivity and accuracy to 97.4% and 91.0%. Methylation markers were positive in 5 of 6 patients with confirmed CCA whose cytology and CA19-9 were negative. CONCLUSIONS: DNA methylation increased the sensitivity for the diagnosis of CCA; therefore, the use of DNA methylation is promising for diagnosis of CCA in patients with biliary strictures. A future validation study is warranted to assess its role in clinical practice. (Clinical trial registration number: NCT04568512.).

Efficacy and safety of EUS-guided hepaticoesophagostomy (EUS-HES) for malignant biliary obstruction: the first case series.

BACKGROUND: EUS-guided hepaticoesophagostomy (EUS-HES) was reported as an alternative procedure when puncture through the esophagus was inevitable. However, the existing data is very limited. We aimed to evaluate the efficacy and safety of EUS-HES in patients with difficult malignant biliary obstruction. METHODS: All cases who underwent EUS-HES at our institute were retrospectively reviewed. RESULTS: A total of 11 patients underwent EUS-HES from January 2011 to December 2017. Five were male, and the mean age was 57.9 ± 6.3 years. The majority of the patients (8 out of 11 patients) had a biliary obstruction caused by cholangiocarcinoma. The technical success was 100%. The mean procedure time was 73.2 ± 37.6 min. The main reason for EUS-HES was the improper alignment of the bile duct due to left lobe hypertrophy. The clinical success was 90.9%. The mean overall survival was 97.8 ± 68.5 days. No major procedure-related complication, particularly pneumomediastinum, occurred. CONCLUSIONS: EUS-HES is a technically feasible and safe procedure to provide biliary drainage, especially in patients with left hepatic lobe hypertrophy. Using a bougie dilator instead of balloon dilation can avoid previously reported complications.

Effectiveness and Safety of a Single 7-French Plastic Stent for Endoscopic Ultrasound-guided Pancreatic Pseudocyst Drainage and Long-term Follow-up Outcomes.

BACKGROUND: Endoscopic ultrasound (EUS)-guided cystogastrostomy with a single 7-French (Fr) double-pigtail stent (DPS) is less popular due to the concern of stent patency. We aimed to assess the effectiveness, complications, and long-term outcomes of a single 7-Fr DPS in the endoscopic drainage of uncomplicated pseudocysts, containing no or minimal (<10%) debris. METHODS: A retrospective review of patients with pancreatic pseudocysts, who underwent EUS-guided cystogastrostomy during 2010-2018, and a systematic review of the literature were conducted. RESULTS: Of 45 patients, 14 patients underwent endoscopic drainage of uncomplicated pseudocysts using a single 7-Fr × 5 cm DPS. The mean cyst size was 10.2 ± 3.5 cm. Stent placement had a 100% technical and clinical success, defined as complete resolution of symptoms and regression of the cyst size by more than 50% at 8 weeks after drainage. The median follow-up was 42.4 months (range, 10-103). The pseudocysts resolved without recurrence in 92.8%. Spontaneous stent dislodgment was noted in 70% at a mean follow-up of 18 months. Additional interventions were required in 14% of cases due to stent occlusion and migration. A systematic review of literature related to EUS-guided cystogastrostomy using single and multiple plastic stents included 9 of 333 studies (222 patients). The analysis showed the pooled clinical success of 89% (95% confidence interval [CI], 82.0-94.2) and complication rate of 13% (95% CI, 5.7-21.8). CONCLUSION: Selected uncomplicated pseudocysts can be treated effectively with a single 7-Fr DPS as it provides comparable clinical success and long-term outcomes as using larger or multiple stents.

Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B.

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients. Methods: Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events. Results: In accordance with Brunt's classification, 408 patients had steatohepatitis (n=34), "steatosis but not steatohepatitis" (n=118), or "non-steatosis" (n=256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events. Conclusions: Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.

Fatty Pancreas: Linking Pancreas Pathophysiology to Nonalcoholic Fatty Liver Disease.

Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired ß-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.

Nontumoral Portal Vein Thrombosis: A Challenging Consequence of Liver Cirrhosis.

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.