Cristiane Valle Tovo

Risks of proton pump inhibitors for patients with cirrhosis: The controversy remains

This letter is in regard to the recently published article by Dam et al. The authors performed a post hoc analysis on data of patients with cirrhosis and ascites who were enrolled in three trials of satavaptan for ascites control. The study demonstrated that the use of proton pump inhibitors (PPIs) was associated with a greater risk of hepatic encephalopathy (HE; hazard ratio 5 1.36, 95% confidence interval 1.01-1.84) and spontaneous bacterial peritonitis (SBP; hazard ratio 5 1.72, 95% confidence interval 1.10-2.69). As highlighted by the authors, a study performed by our group reached different results regarding the association between PPIs and SBP: 22.5% of PPI users and 21.5% of PPI nonusers developed SBP (P 5 0.176). An Argentinean study also failed to detect a significant association between PPI use and SBP. Despite the merits of the study by Dam et al., we understand that some issues about it need further discussion. The first issue is that because it was a post hoc analysis, the authors were unaware of the PPI use status during the follow-up. The variability of PPI use over time was pointed out as a limitation of the study by the authors themselves. Moreover, the fact that 33% of PPI users and only 14% of nonusers received lactulose at baseline implies that PPI users already had episodes of HE (which was supposed to be an exclusion criterion of the study) or were at a higher risk for developing it. When only lactulose nonusers were evaluated, the impact of PPI on HE was actually lost (95% confidence interval included the null value). The difference in the percentage of use of lactulose led us to believe that patients using PPIs were probably more severely ill than the others. Still, concerning lactulose, the authors considered that its use was a predictor of HE, which we do not agree with because we understand that patients using lactulose probably already had HE. Thus, we believe that the findings of the study by Dam et al. should be interpreted carefully and that more studies are required in order to abate the controversy regarding this subject. Nevertheless, we suggest that physicians avoid the indiscriminate prescription of PPIs. Ângelo Zambam de Mattos, M.D., M.Sc., Ph.D. Suelen Aparecida da Silva Miozzo, M.D., M.Sc. Cristiane Valle Tovo, M.D., M.Sc., Ph.D. Angelo Alves de Mattos, M.D., M.Sc., Ph.D. Gastroenterology and Hepatology Unit Pontifical Catholic University of Rio Grande do Sul Porto Alegre, Brazil Gastroenterology and Hepatology Unit Irmandade Santa Casa de Miseric ordia de Porto Alegre Porto Alegre, Brazil Post-Graduation Course of Hepatology Federal University of Health Sciences of Porto Alegre Porto Alegre, Brazil Gastroenterology and Hepatology Unit Nossa Senhora da Conceiç~ao Hospital Porto Alegre, Brazil