Investigation Of The Effects Of Proton Pump Inhibitors On Endoscopic Therapy Of Gastro-oesophageal Varices In Liver Cirrhosis:A Randomized Controlled Trial

BackgroundLiver cirrhosis is the end stage of chronic liver diseases which caused by various causes.Portal hypertension related gastro-oesophageal varices(GOV)is one of the most common complications of liver cirrhosis.Acute Gastrointestinal hemorrhage caused by rupture of GOV is menacing and life-threatening.With the continuous development of endoscopic technology in recent years,endoscopic therapy has become the cornerstone of managements of liver cirrhosis with GOV,including endoscopic variceal ligation(EVL)or/and endoscopic tissue adhesive(ETA)and so on.Proton pump inhibitors(PPIs)are used widely in clinical practice which can inhibit gastric acid secretion and have been proven effective in acid-related diseases and non-variceal upper gastrointestinal bleeding.However,it remains controversial whether PPIs should be used in liver cirrhosis with GOV after endoscopic therapy.Therefore,investigating the effects of PPIs on liver cirrhosis with GOV after endoscopic therapy has important clinical significanceAimThe aim of this study was to evaluate the effects of PPIs on liver cirrhosis with GOV after endoscopic therapy,including bleeding rate,mortality rate,rate of adverse events after endoscopic therapy,hospital stays and costs.MethodsFrom May 2017 to June 2019,liver cirrhotic patients with GOV who hospitalized and received endoscopic therapy at Qilu Hospital of Shandong University were randomized,included primary prophylaxis,acute bleeding and secondary prophylaxis.Eligible patients were randomized into two groups:1.Combined PPIs and endoscopic therapy group:continuous intravenous PPIs(pantoprazole or esomeprazole 80 mg per day)and then oral PPIs(pantoprazole or esomeprazole 80 mg per day)for 14 days totally after endoscopic therapy;2.Alone endoscopic therapy group:without PPIs treatment after endoscopic therapy.Inclusion criteria included:1)?18 years;2)Diagnosis of cirrhosis caused by various causes;3)confirmed GOV with endoscopy,with or without bleeding.Exclusion criteria include:1)Acute gastrointestinal bleeding which need emergency surgery;2)Gastroesophageal reflux disease or peptic ulcer which need treatment of gastric acid suppression;3)Hepatocellular carcinoma or other malignant tumors;4)History of esophagus,stomach,gallbladder,pancreas or liver surgery;5)Child-Pugh classification of liver function is grade C,and can't be improved to grade A or B;6)Severe diseases of respiratory or circulatory system or other system;7)Preparing to be pregnant,pregnant or breast-feeding;8)Allergic or intolerable to PPIs;9)Cannot provide informed consent.Results209 subjects were assessed for inclusion,and a total of 106 eligible patients were randomized into alone endoscopic therapy group or combined PPIs and endoscopic therapy group finally.There were no significant differences in baseline date between two groups,such as age(P=0.76),gender(P=0.67)and liver function grading(P=0.59).Results showed that the total bleeding rate was 5.66%(3/53)in two groups during 8 weeks follow-up period.Among those-bleeding patients,there were 2 secondary prophylactic patients(2/30,6.67%)and 1 acute bleeding patient(1/9,11.11%)in the alone endoscopic therapy group;and 1 primary prophylactic patient(1/12,8.33%)and 2 acute hemorrhage patients(2/9,22.22%)in the combined PPIs and endoscopic therapy group,no statistical differences existed(P>0.05).1 patient in the combined PPIs and endoscopic therapy group died of acute variceal bleeding on 16th days after endoscopic therapy,and no death occurred in the alone endoscopic therapy group within 8 weeks after endoscopic therapy.The difference of mortality between the two groups was not statistically significant(P>0.05).The incidence of overall adverse events after endoscopic therapy in the combined PPIs and endoscopic therapy group was 28%(15/53),and 38%(20/53)in alone endoscopic therapy group,the difference was also not significant statistically(P=0.30).Furthermore,the average hospital stays of the PPIs plus endoscopic therapy group was longer than the endoscopic treatment alone group(9.92 days vs.9.06 days)and the average costs of hospitalization were higher(23,626 yuan vs.19,220 yuan,P<0.05).ConclusionCompared with endoscopic therapy alone,PPIs combined with endoscopic therapy do not reduce the rate of variceal bleeding,mortality and adverse events of liver cirrhosis patients with GOV.In addition,those patients received PPIs plus endoscopic therapy had a longer hospital stay and a higher cost of hospitalization.SignificanceThrough comparing the results of combined PPIs and endoscopic therapy and endoscopic therapy alone on liver cirrhosis with GOV,this study investigated the effects of PPIs on liver cirrhosis with GOV after endoscopic therapy,including bleeding rate,mortality rate,rate of adverse events after endoscopic therapy,hospital stays and costs.The results showed that PPIs combined with endoscopic therapy do not reduce rate of variceal bleeding,mortality and endoscopic therapy-related adverse events in liver cirrhosis with GOV.In addition,those patients received PPIs plus endoscopic therapy had a longer hospital stay and a higher cost of hospitalization.These results provided evidence-based evidence for the clinical use of PPIs in liver cirrhosis with GOV after endoscopic therapy.