The safety of nonselective b-blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006-2008 and included 1198 cirrhosis patients with ascites followed for 1 year. We used Cox regression to compare allcause mortality and cirrhosis-related mortality between patients who did and those who did not use NSBBs at randomization, controlling for age, gender, Model for End-Stage Liver Disease score, Child-Pugh score, serum sodium, previous variceal bleeding, cirrhosis etiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomization, the 559 NSBB users were more likely than the 629 nonusers to have a history of variceal bleeding but less likely to have Child-Pugh class C cirrhosis, hyponatremia, or refractory ascites. The 52-week cumulative all-cause mortality was similar in the NSBB user and nonuser groups (23.2% versus 25.3%, adjusted hazard ratio 5 0.92, 95% confidence interval 0.72-1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted hazard ratio 5 1.02, 95% confidence interval 0.74-1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis-related mortality (adjusted hazard ratio 5 1.00, 95% confidence interval 0.76-1.31). During follow-up, 29% of initial NSBB users stopped taking NSBBs, and the decision to stop NSBB treatment marked a sharp rise in mortality and coincided with hospitalization, variceal bleeding, bacterial infection, and/or development of hepatorenal syndrome. Conclusion: This large and detailed data set on worldwide nonprotocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase mortality; the decision to stop NSBB treatment in relation to stressful events may have added to the safety. (HEPATOLOGY 2016;63:1968-1976 SEE EDITORIAL ON PAGE 1771U se of nonselective b-blockers (NSBBs) as secondary prevention of variceal bleeding was introduced in 1981. (1) Since then, numerous randomized trials and meta-analyses have documented NSBBs' efficacy in preventing variceal bleeding, (2,3) and today NSBBs are the standard pharmacological treatment for primary and secondary prevention of variceal bleeding. (4,5) They reduce portal pressure by decreasing cardiac output (b 1 -blockade) and splanchnic blood flow (b 2 -blockade). (6) Surprisingly, in 2010 serious concerns about the safety of NSBB use in cirrhosis patients with refractory ascites were raised by a single-center observational Abbreviations: CI, confidence interval; HR, hazard ratio; HRS, hepatorenal syndrome; MAP, mean arterial pressure; MELD, Model for End-Stage Liver Disease; NSBB, nonselective b-blocker; SBP, spontaneous bacterial peritonitis.

Histologically verified hepatocellular adenoma is rare in Denmark. It is a minor concern for women, but men have a very high risk of progression to HCC.

Background & Aims Many patients with cirrhosis use proton pump inhibitors. We aimed to determine their effects on the risk and prognosis of infections in patients with cirrhosis and ascites. Methods We used data from three 1‐year trials of satavaptan treatment of ascites (N = 1198) to compare incidence and 90‐day mortality of first‐time infections between users and nonusers of proton pump inhibitors. With standard and marginal structural Cox models, we adjusted for differences in gender, age, cirrhosis aetiology, Model for End‐stage Liver Disease score, serum albumin, lactulose use, severity of ascites, and history of spontaneous bacterial peritonitis or variceal bleeding. Results During the follow‐up, 446 patients had an infection. At inclusion, 524 patients (44%) used proton pump inhibitors, and 645 (54%) used them at some point during the follow‐up. Proton pump inhibitor use increased the rate of infections overall (adjusted hazard ratio = 1.43, 95% CI 1.18‐1.74), and it also increased the rate of all specific types of infections except upper respiratory tract infections of presumably viral origin. The estimated cumulative risk of infections was 36.4% for proton pump inhibitor users vs 25.1% for nonusers at 6 months (relative risk = 1.45, 95% CI 1.22‐1.73), and 45.2% vs 37.7% at 1 year (relative risk = 1.20, 95% 0.97‐1.40). Use of proton pump inhibitors did not affect mortality during the 90 days following infection (adjusted hazard ratio = 0.83, 95% CI 0.53‐1.31). Conclusions Approximately half of patients with cirrhosis and ascites use proton pump inhibitors. This use increases their risk of bacterial infections, but does not affect their prognosis after an infection occurs.

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