| Background:Cirrhosis is an advanced stage in the development of various chronic liver diseases.Clinically,the main manifestations of decompensated cirrhosis patients are liver dysfunction and portal hypertension,such as gastroesophageal varices,splenomegaly and hypersplenism.The most common complications that directly result from portal hypertension are the development of varices and variceal hemorrhage in cirrhosis patients.The variceal rebleeding is closely related to the high mortality rate.Therefore,appropriate treatment for the prevention of variceal rebleeding is very important.The Baveno VI consensus and the domestic consensus on diagnosis and management of gastroesophageal varices bleeding in liver cirrhosis patients with portal hypertension have provided guidance for the prevention and management of gastroesophageal varices bleeding.However,the treatment of splenomegaly and hypersplenism in those patients is not mentioned.The prevalence of splenomegaly is about 52%in cirrhosis patients,while another 13%patients are suspiciously combined with splenomegaly.Splenomegaly and portal hypertension reinforce mutually in cirrhosis patients with advanced stage.When platelet<100000/mm3 is defined as severe hypersplenism,the incidence of severe hypersplenism in cirrhosis is about 33%.Endoscopic variceal ligation(EVL)is the endoscopic treatment for cirrhosis patients with acute esophageal varices bleeding.Partial splenic embolization(PSE)is an effective treatment for hypersplenism.Studies have shown that when 50%infarction volume of the spleen was achieved by PSE,the portal vein pressure will reduce 20%immediately.PSE can significantly decrease splenic blood flow,splenic venous pressure,and improve portal hemodynamics in cirrhotic patients[1].Although some small single-center studies have shown that EVL plus PSE is more effective in preventing the bleeding of varices than EVL alone in cirrhosis patients.EVL plus PSE can reducing the rebleeding rate by 12-39%than EVL alone[2].However,the long-term effects of EVL+N-Butyl-2 Cyanoacrylate injection+PSE are rarely reported in cirrhosis patients with gastroesophageal varices and further studies are required.In this study,EVL+N-Butyl-2 Cyanoacrylate injection were collectively referred to endoscopic intervention.Endoscopic intervention has been accepted worldwide as a treatment for gastroesophageal varices bleeding.However,whether patients with splenomegaly and hypersplenism should be treated with PSE needs further studied.We conduct a prospective multicenter randomized controlled trial to explore the prognostic effects of different treatment options for secondary prophylaxis of gastroesophageal varices in cirrhosis patients with splenomegaly and hypersplenism.Objective:To explore the efficacy of endoscopic intervention combined with PSE treatment versus endoscopic intervention alone for secondary prophylaxis of gastroesophageal varices in cirrhosis patients with hypersplenism and thrombocytopenia.Methods:1.The enrollment criteria:cirrhosis patients with hypersplenism and thrombocytopenia(platelet<75,000/mm3)caused by portal hypertension who have survived from acute variceal bleeding 5 days later.2.From June 2016 to December 2019,107 patients were enrolled in this trial,70 patients from Qilu Hospital of Shandong University,12 patients from Shandong Provincial Hospital,and 25 patients from The 960th Hospital of the PLA Joint Logistice Support Force.Among them,51 patients underwent endoscopic intervention+PSE.The other 56 patients were treated with endoscopic intervention alone.In the endoscopic group,EVL was performed for the esophageal varices and N-Butyl-2 Cyanoacrylate injection for the gastric varices.EVL was repeated every 4 weeks until complete eradication of varices was achieved and the tissue adhesive injection will be repeated if necessary.In the endoscopic+PSE treatment group,PSE was performed initially until there was a 50%to 70%reduction in splenic blood flow.Then the endoscopic intervention will underwent after 1 week until complete eradication of varices was achieved.3.The blood routine index,liver function index,coagulation function index,Child-Pugh score and Child-Pugh grade of the patients were recorded before treatment,after treatment,and at 3 months,6 months,1 year and 2 years.During the follow-up,abdominal plain scan+enhanced CT were performed to determine the volume of the spleen and the infarction volume of spleen.Follow-up endoscopy was performed to observe the recurrence of gastroesophageal varices and recorded the time from the end of the treatment.Record whether the patients suffered from rebleeding in the outpatient clinic or telephone follow-up and record the time to the initial treatment.The end point of study was 2 years after treatment or death.4.Analyze and compare the red blood cell,white blood cell,platelet,hemoglobin,alanine aminoaminotransferase,aspartate aminotransferase,alkaline phosphatase,albumin,total bilirubin,prothrombin time,international normalized ratio,prothrombin activity,Child-Pugh score and Child-Pugh grade between the two groups before/after the treatment and during the follow-up.Analyzing and comparing the risk of variceal recurrence and variceal rebleeding between the two groups,and identifying the relevant factors that affecting the recurrence and rebleeding of varices.Results:The two groups were well matched with respect to age,gender,etiology,Child-Pugh score,Child-Pugh class,degree of varices and all hematological indicators(P>0.05).At the end of treatment of endoscopic+PSE group,the levels of leukocyte,red blood cell,platelet and albumin were significantly improved when compared with the endoscopic intervention alone(P<0.05)and those hematological indicators were improved in the 2 years follow-up,especially the platelet levels(P<0.05).In endoscopic+PSE group,the level of white blood cell,red blood cell,platelet,hemoglobin,albumin,prothrombin time,international standardized ratio,prothrombin activity and Child-Pugh score were improved significantly during 2years follow-up.Neither alanine aminoaminotransferase studied significant changed during the follow-up in endoscopic+PSE group.While aspartate aminotransferase and alkaline phosphatase were increased significantly during follow-up in endoscopic+PSE group(P<0.05),but the level didn't reach 3 times the upper limit of normal.In endoscopic intervention group,the level of erythrocyte and hemoglobin were significantly improved(P<0.05)and the level of other hematological indicators didn't show significant change,while the platelets counts showed a decline during the follow-up.The recurrence rate of varices in the endoscopic+PSE group was significantly lower than that in the endoscopic intervention group(x2=29.842,P<0.05).During the follow-up,11 cases(22%)in the endoscopic+PSE group and 36 cases(64%)in the endoscopic intervention group had developed new varices requiring further endoscopic intervention.The median time of varices recurrence in the endoscopic group was 11 months.The COX proportional hazard analysis models identified only one independent factor that influenced the recurrence of varices,which was treatment options.The hazard ratio of varices recurrence was 5.618 times in the endoscopic intervention group than that in endoscopic+PSE group,with a 95%confidence interval(2.786-11.364).The rebleeding rate of varices in the endoscopic+PSE group was significantly lower than that in the endoscopic intervention group(?2=7.061,P<0.05).During the follow-up,8 cases(16%)in the endoscopic+PSE group,and 17 cases(30%)in the endoscopic intervention group suffered from varices bleeding.The median time of varices rebleeding in the endoscopic group was 41 months.The COX proportional hazard analysis models identified only one independent factor that influenced the rebleeding of varices,which was treatment options.The hazard ratio of varices rebleeding was 4.587 times in the endoscopic intervention group than endoscopic+PSE group,with a 95%confidence interval(1.603-13.158).Conclusions:The endoscopic+PSE treatment can significantly increase the counts of white blood cell,red blood cell,platelet,albumin when compared with the endoscopic intervention group during 2years follow-up.The endoscopic+PSE treatment significantly improved the peripheral blood cell counts,liver synthesis function and coagulation function during 2years follow-up.The endoscopic+PSE treatment can significantly reduce the risk rate of variceal recurrence and variceal rebleeding.This combination therapy is a safe and effective treatment for secondary prophylaxis of gastroesophageal varices in cirrhosis patients with hypersplenism and thrombocytopenia. |
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