The Efficacy of Proton Pump Inhibitor in Cirrhotics with Variceal Bleeding: A Systemic Review and Meta-Analysis.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) was widely used in cirrhotic patients with variceal bleeding empirically rather than evidence-based practice. We aimed to evaluate the plausible indication of PPI use in variceal bleeding cirrhotic patients and figure out whether it can decrease the re-bleeding rate after endoscopic therapy. Furthermore, we also investigated the association between PPI and bleeding-related mortality in these patients. METHODS: We have searched in PubMed, Medline, Web of Science, Google Scholar, Cochrane and Embase prior to May 2019. Pooled OR and 95% CI were calculated by random-effects model. RESULTS: A total of 11 original articles including 1,818 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use may decrease the re-bleeding rate after endoscopic therapy (OR 0.52, 95% CI 0.35-0.77). The conclusion was irrespective of study methods, endoscopic purpose and hemorrhage sites. However, the conclusion speculated that PPI should be prescribed >1 month. Meanwhile, PPI use may not impact the bleeding-related mortality. CONCLUSIONS: PPI, used for >1 month, can decrease re-bleeding rate after endoscopic therapy in cirrhotic patients for prophylaxis or emergency treatment purpose. No matter how long it takes, PPI use is not associated with bleeding-related mortality.

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.

[Impact of portal vein thrombosis on the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis].

Objective: To explore whether portal vein thrombosis affects the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis. Methods: Hospitalized patients who received endoscopic therapy to prevent re-bleeding from ruptured gastroesophageal varices due to hepatitis B-related liver cirrhosis during 2013 to 2017 were selected, and followed up for 1 year after treatment for re-bleeding and survival status. Patients were divided into thrombotic and non-thrombotic group according to whether they were combined with portal vein thrombosis at the time of initial admission. The baseline data characteristics of the two groups were analyzed. The 1-year re-bleeding rate and survival rate of the two groups were compared by Kaplan-Meier survival analysis. The other risk factors for re-bleeding after endoscopic variceal therapy were evaluated by univariate and multivariate regression. Results: A total of 124 cases with re-bleeding from ruptured gastroesophageal varices due to hepatitis B-related liver cirrhosis were included. The average age was 50.7 years old. 81.5% (101 cases) were male, and 24.2% (30 cases) were combined with portal vein thrombosis. There were no statistically significant differences between the thrombotic and the non-thrombotic group in the average age, gender, liver function classification, transjugular portal pressure gradient, antiviral treatment, and non-selective ß-blockers. Kaplan-Meier analysis of the re-bleeding rate after endoscopic treatment indicated that the incidence of non-bleeding in patients with thrombotic group at 60 days, 180 days and 1 year was significantly lower than that in the non-thrombotic group [86.7%, 80.0%, 56.7% vs. 95.7%, 93.6%, 87.2% (P = 0.000 1)]. Analysis of the location of portal vein thrombosis showed that the bleeding rate in the main portal trunk, left and right branches and superior mesenteric vein had increased significantly after endoscopic treatment, while the splenic vein had no effect on the bleeding after endoscopic treatment. Univariate and multivariate regression analysis indicated that age (HR 1.05, 95% CI: 1.01-1.09, P = 0.02) and thrombosis in the main portal trunk, left and right branches (HR 4.95, 95% CI: 2.05-11.95, P < 0.01) were independent risk factors for re-bleeding at 1 year after endoscopic treatment. Conclusion: Portal vein thrombosis is an independent risk factor that affects the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis and the risk of re-bleeding increases significantly after endoscopic treatment in patients with thrombosis.

[Gastroesophageal variceal bleeding in cirrhotic patients: the possibilities of effective hemostasis]. / Varikoznye pishchevodno-zheludochnye krovotecheniia pri tsirroze pecheni: vozmozhnosti éffektivnogo gemostaza.

AIM: To improve the results of treatment of gastroesophageal variceal bleeding (GEVB) in cirrhotic patients with thrombocytopenia. MATERIAL AND METHODS: A total experience of the clinic includes 338 GEVB patients, endoscopic variceal ligation (EVL) and transjugular intrahepatic portosystemic shunt (TIPS) were performed in 162 and 157 cases respectively. Nevertheless, just the efficacy of initial pharmacological hemostatic therapy was analyzed. RESULTS: Administration of serotonin adipinate 30-50 mg/day during 3-5 days in addition to standard initial therapy allowed us to achieve permanent hemostasis during initial treatment if EVL was impossible. Serotonin adipinate induces thrombocytes' adhesion and improves fibrin clot strength. This therapy markedly decreases mortality (33.3% vs 46.7%), incidence of recurrent bleeding (46.4% vs 60.0%). Also it contributes successful hemostasis with endoscopic ligation and effective portal decompression by TIPS procedure.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients.

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis (LC) patients according to the current guidelines. Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients. Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology. According to the current guidelines, in the absence of clinically significant portal hypertension, etiological and non-etiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding, whereas its presence serves as an indication for the administration of non-selective ß-blockers, among which carvedilol is the drug of choice. Non-selective ß-blockers, as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding. Pharmacotherapy with vasoactive drugs (terlipressin, somatostatin, octreotide), endoscopic variceal ligation, endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding. Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management, avoiding the first and further decompensation in LC, which will improve the prognosis and survival of patients suffering from it.

Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications.

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, etc., will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Clip-Assisted Endoscopic Cyanoacrylate Injection: A Novel Technique for Acute Gastroesophageal Variceal Bleeding.

Background and Aim: Endoscopic injection sclerotherapy is effective for the treatment of gastric variceal bleeding, but may cause fatal ectopic embolism. Spontaneous portosystemic shunts are one of the risk factors for ectopic embolism. This present study aims to evaluate the efficacy and safety of clip-assisted endoscopic cyanoacrylate injection for the treatment of acute gastroesophageal variceal bleeding. Methods: The medical records of patients with gastroesophageal varices (GOVs) who underwent clip-assisted cyanoacrylate injection at the Ningbo First Hospital from March 2017 to August 2020 were reviewed. The outcomes were immediate hemostasis rate, early rebleeding rate, late rebleeding rate, and procedure-related complications. The gastrorenal and splenorenal shunts were evaluated by the computed tomography angiography. Results: A total of 9 patients with GOVs (GOV1 and GOV2) were analyzed, and 4 of the patients had spontaneous portosystemic shunts. The average number of clips used in each patient was 2.11 ± 1.96, and an average of 5.11 ± 1.76 mL of cyanoacrylate was injected into each patient. All patients completed immediate hemostasis. Two patients experienced rebleeding, including 1 case of early rebleeding and 1 case of late rebleeding (both due to cyanoacrylate extrusion) during a median follow-up of 367 days (interquartile range 270-855 days). Five patients underwent follow-up endoscopy; eradicated gastric varices (GVs) were revealed in 1 patient, and shrunken GVs were found in 4 patients. No serious complications, including ectopic embolism, were observed. Conclusion: The present study showed the efficacy and safety of clip-assisted endoscopic cyanoacrylate injection in acute GOV bleeding, but these results require verification by randomized controlled studies with larger sample numbers.

Transjugular Intrahepatic Portosystemic Shunt Placement in Patients with Schistosomiasis-Induced Liver Fibrosis.

PURPOSE: Evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) insertion on patients with schistosomiasis-induced liver fibrosis, and compare with that of patients with HBV-induced cirrhosis. MATERIALS AND METHODS: This was a retrospective study from November 2015 to December 2018 including 82 patients diagnosed with portal hypertension, one group of which is induced by schistosomiasis (n = 20), the other by hepatitis B virus (HBV) (n = 62). Both groups of subjects underwent TIPS placement for the management of portal hypertension complications. RESULTS: TIPS was inserted successfully in all patients (technical success 100%). After a median follow-up of 14 months following TIPS insertion, portal pressure gradient (PPG) value in both schistosomiasis-induced group and HBV-induced group underwent a significant decrease with no major difference between the two groups. There exists no significant difference demonstrated by Kaplan-Meier curves between two groups concerning cumulative rate of hepatic encephalopathy (HE) (log-rank p = 0.681), variceal rebleeding (log-rank p = 0.837) and survival (log-rank p = 0.429), and no statistically difference was found in terms of alleviation of portal vein thrombosis (PVT). In addition, splenectomy (HR 19, 95% CI 4-90, p < 0.001) was identified as independent predictor of PVT. CONCLUSIONS: TIPS placement is well-founded to be considered as a safe and effective treatment in patients with schistosomiasis-induced portal hypertension and relevant severe complications. We also found the risk of PVT is 19 times higher in patients who underwent splenectomy than in untreated patients. LEVEL OF EVIDENCE: Historically controlled studies, level 4.

Natural History of Cirrhosis of Liver after First Decompensation: A Prospective Study in India.

BACKGROUND AND AIMS: As liver cirrhosis is a dynamic condition, it is possible to improve survival in decompensated cirrhosis. Hence, we planned a prospective study to determine the natural history of cirrhosis after first decompensation. METHODS: We enrolled all patients of liver cirrhosis who presented with first episode of decompensation defined by the presence of ascites, either overt or detected by Ultrasonography (UD), Gastroesophageal Variceal Bleeding (GEVB), and Hepatic Encephalopathy (HE). All patients were followed up to death/liver transplant or at least for the period of 1 year. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or Orthotopic Liver Transplantation (OLT)). RESULTS: In total of 110 cirrhotic patients (93 males, mean age 50 ± 11 years), the most frequent etiology was alcohol (48%), followed by nonalcoholic steatohepatitis/cryptogenic (26%), hepatitis B (10%), autoimmune hepatitis (7%), and hepatitis C (6%). The distribution of CTP classes was: 4%, 56%, and 41% in class A, B, and C, respectively. Ascites was the most common decompensation found in 88 patients (80%) followed by HE (14%) and GEVB (6%). At 1-year follow up, transplant free survival was 78%, 2 underwent OLT, 4 developed hepatocellular carcinoma, and 24 died. Cumulative incidence of failure (death or OLT) by type of decompensation after 1 year was: 22% overt ascites, 50% GEVB, 28% UD ascites, 20% HE, and 33% ascites and GEVB concomitant. CONCLUSIONS: Patients with UD ascites do not have a negligible mortality rate as compared to overt ascites. Patients with cirrhosis after first decompensation have better transplant free survival with treatment of etiology and complications than previously mentioned in literature.