Peptic ulcer bleeding in patients with cirrhosis: Is it as bad as variceal bleeding?
Authors: Gin‐Ho Lo, Thomas Reiberger
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Reiberger consults and received grants from Gilead, MSD and AbbVie. He is on the speakers' bureau and received grants from Gore. He received grants from Phillips. See Article On Page 1458 The fox changes his skin but keeps the rogue. German Proverb Peptic ulcer bleeding (PUB) is among the most common causes of hospitalization worldwide; however, advances in endoscopic and pharmacological therapies have reduced the case fatality rate to 2.1%.1 In contrast, 6‐week mortality of acute variceal bleeding (AVB) remained as high as 20%.2 Despite the considerable incidence of peptic ulcers with 6%‐33% and high recurrence rate of PUB in patients with cirrhosis,4 the specific mechanisms responsible for peptic ulcers remain largely unknown in the setting of cirrhosis.4 In this issue of Hepatology, Ardevol et al. report on a comparison of survival between PUB and AVB in patients with cirrhosis.5 This multicenter retrospective study enrolled 646 patients with AVB and 144 patients with PUB. All the patients were managed with current first‐line therapies, such as antibiotic prophylaxis and emergency endoscopic therapy, within 6 hours of presentation. Child‐Pugh class and Model for End‐Stage Liver Disease scores were similar between both groups. However, as compared to AVB patients, PUB patients had a higher incidence of alcoholism, use of nonsteroidal anti‐inflammatory drugs or aspirin, shock at admission, a higher Charlson index, and lower hepatic venous pressure gradient. The results showed that the rebleeding rate of 26% in AVB patients was significantly higher than the figure of 10% in patients with PUB at 45 days. However, mortality at 45 days—19% in the AVB group and 17% in the PUB group—was quite similar in both groups. Only 2% of the ulcer bleeding group and 3% of the variceal bleeding group died of uncontrolled bleeding. The causes of death were usually related to hepatic failure or comorbidities. This cohort study suggested that the issue of PUB in patients with cirrhosis should not be regarded as usual ulcer bleeding. Actually, PUB in patients with cirrhosis may be as severe as AVB. Likely due to selection bias, the prognosis of PUB in patients with cirrhosis varied greatly among studies. In‐hospital mortality as low as 3%‐4% in PUB among patients with cirrhosis has been recorded.6 These figures were quite close to that in the general population. Approximately 30 years ago, our study already demonstrated that the case fatality in patients with cirrhosis with PUB was around 20%, significantly higher than that in patients without cirrhosis.3 A recent study from France showed that in‐hospital mortality was significantly greater in patients with cirrhosis as compared to the general population (17.4% vs. 4.7%).8 Crooks et al., in England, showed that 28‐day mortality following PUB was reduced from 14.7% in 1999 to 13.1% in 2007. The corresponding figure associated with AVB was 24.6% and 20.9%, respectively.9 The mortality of around 13%‐17% in patients with cirrhosis with PUB by these studies revealed that the improvement of survival in patients with cirrhosis made little progress, even though highly successful hemostasis of PUB was achieved in the two recent decades. In this study, the mortality rate of AVB was 19% at 45 days, akin to other studies. The mortality rate of AVB may be lower than 10% in some studies.10 Still, there is room for further improvement in reducing PUB‐associated mortality in patients with cirrhosis. Owing to advances in endoscopic and pharmacological treatment, an appreciably low incidence of uncontrollable bleeding was noted in either PUB or AVB. As shown in the current study, only 2% of PUB and 3% of AVB in patients with cirrhosis died of uncontrolled bleeding. Most studies revealed that aging and comorbidities are important factors associated with mortality in upper gastrointestinal bleeding.1 Similarly, the majority of either AVB or PUB in the current study died of liver failure or multiorgan failure.5 When patients have concomitant peptic ulcers and gastroesophageal varices, the accurate sources of bleeding pose a challenge to endoscopists. If there were no red color signs on varices and no stigmata of recent hemorrhage on peptic ulcers, the researchers ascribed this to PUB. Actually, this definition may elicit controversy, given that patients with AVB without active bleeding at endoscopy may have been misclassified as PUB, thus, potentially overestimating, the bad outcomes of the PUB group. However, this "definition" accounted for only 25 patients, and after exclusion of these patients, the researchers could still demonstrate that the survival was still similar between both groups of AVB and PUB patients. Regarding the etiologies of peptic ulcers in the current study, 29% were related with Helicobacter pylori and 46% were deemed as idiopathic.5 It is noted that the incidence of rebleeding may be up to 42% among patients with idiopathic ulcers.1 We have demonstrated that eradication of H. pylori infection could not prevent ulcer recurrence.3 It warrants further study to assess whether beta blockers4 or acid suppression agents1 could be used in the prevention of recurrent peptic ulcers and recurrent PUB. In summary, the study by Ardevol et al. emphasized the importance of PUB in patients with cirrhosis. PUB has a lower rebleeding rate; however, the mortality could be as grave as AVB. The screening of peptic ulcers and the prevention of PUB in patients with cirrhosis may be as important as the management of gastroesophageal varices. To reduce the mortality of either PUB or AVB in patients with cirrhosis, optimization of management in reducing the risk of bleeding impact on liver failure or multiorgan failure, instead of focusing merely on successful hemostasis, should be implemented.