AVB in patients with liver cirrhosis is a common clinical critical disease, with a 6-week
mortality rate as high as 20%. Currently, many guidelines recommend the use of vasoactive
drugs (terlipressin, somatostatin or octreotide) combined with endoscopic therapy (Endoscopic
Variceal Ligation (EVL), endoscopic injection sclerotherapy (EIS) and the use of prophylactic
antibiotics for patients with AVB.
PPI is a commonly used antacid agent, which has a significant antacid effect, protects the
gastrointestinal mucosa, promotes blood coagulation, healing ulcers, effectively stops
bleeding and prevents rebleeding. There is a consensus that PPI should be used before and
after endoscopic therapy in patients with non-variceal acute bleeding. However, studies on
the efficacy of PPI after EVL are still limited and lack of sufficient convincing. In a
randomized controlled study, pantoprazole treatment was found to be associated with
significantly smaller ulcers 10 days after elective EVL in secondary prevention patients with
cirrhosis. Another randomized controlled study in 2013 found that patients with cirrhosis and
AVB treated with PPI for 19 days after endoscopic hemostasis had smaller ulcers and fewer
overall side-effects, but there was no statistically significant difference in rate of 5-day
treatment failure, 6-week rebleeding rate and 6-week mortality. In 2017, a study included 637
patients with acute bleeding from liver cirrhosis, 80% of whom were treated with acid
suppression therapy, and the study found that acid suppression therapy had no significant
effect on long-term bleeding rate and mortality. However, negative effects of PPI have been
reported in patients with cirrhosis, such as spontaneous bacterial peritonitis and hepatic
encephalopathy. It is found that patients with cirrhosis and ascites had an increased risk of
first hepatic encephalopathy with PPI use, and also found that patients with cirrhosis had an
increased risk of hepatic encephalopathy and death with PPI use. Therefore, PPI use in
patients with cirrhosis should be more cautious. However, the duration of PPI use in these
studies was long, and there are no data to clarify the effect of short-term PPI use.
At present, there is no consensus among the major guidelines on the use of PPI in patients
with acute AVB in liver cirrhosis, and the UK guidelines do not recommend the use of PPI
unless accompanied by gastrointestinal ulcer. The use of PPI was not mentioned in the
guidelines of the American Endoscopic Society and the European Endoscopic Society. The 2021
Baveno 7 guideline clearly proposes that PPI should be stopped immediately once AVB is
identified as cirrhosis. The latest meta-analysis in 2022 showed that the use of PPI before
endoscopy may reduce the need for endoscopic hemostasis in patients with upper
gastrointestinal tract, but there was no sufficient evidence to confirm the effect on
clinical outcomes including 30-day mortality and rebleeding. It can be concluded that there
is no consensus on the use of PPI in patients with AVB in cirrhosis, and the recommendations
of guidelines lack high-quality studies to improve the convincing.
In summary, there is little evidence for the effect of PPI use in patients with AVB in liver
cirrhosis, and there is no study on the efficacy of PPI combined with endoscopic therapy in
patients with AVB in liver cirrhosis. Therefore, the investigators planned to design a
multicenter prospective randomized controlled trial to explore the efficacy of PPI in
cirrhotic patients with AVB. In this study, the following questions were investigated: 1. Can
PPI reduce the 5-day treatment failure rate in cirrhotic patients with AVB; 2. Can it reduce
the 6-week rebleeding rate, mortality, and complications in patients with liver cirrhosis and
AVB.