Sustained impact of nosocomial-acquired spontaneous bacterial peritonitis in different stages of decompensated liver cirrhosis.

BACKGROUND & AIMS: Bacterial infections, in particular a spontaneous bacterial peritonitis (SBP), are a major threat in patients with liver cirrhosis. Recently, it has been shown that the impact on mortality might be underestimated by established risk-scores. Onset of infection was suggested to define a distinct stage of cirrhosis. However, it remains unclear whether all stages of decompensated cirrhosis are equally affected. Moreover, if there is such a distinct stage, it must be determined whether it is reversible after the infection has resolved. In this study we aimed to further analyze the impact of a current as well as a resolved SBP in different stages of decompensated liver cirrhosis. METHODS: A number of 579 patients with liver cirrhosis and ascites were included. MELD-score was used to determine the stage of liver disease. Low (<15), intermediate (15-25) and high (>25) MELD-groups were compared. Patients were followed up for 90 days. Primary endpoint was overall mortality. Statistical analyses were performed using the log-rank test, Cox regression and competing risk analysis. RESULTS: Mortality was significantly higher in patients with nosocomial-acquired SBP (nSBP) compared to patients without SBP (p<0.001;HR = 2.05). However, the most prominent difference in mortality was documented in the intermediate MELD-group (nSBP: p = 0.02;HR = 2.10). Importantly, mortality in nSBP patients remained increased even after the initial nSBP episode had resolved (p<0.01;HR = 1.90). Again, this was only significant in those with intermediate MELD-scores (p = 0.02;HR = 2.28). While a current as well as a resolved nSBP were significantly linked to a higher mortality, neither of them did increase the likelihood for liver transplantation. CONCLUSIONS: Development of nSBP is independently associated with increased mortality supporting the concept of a distinct status of cirrhosis. Importantly, the prognosis remains unfavorable even after resolution of nSBP. This could be particularly relevant for patients with intermediate MELD-scores, who have limited chances for a donor liver.

The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients.

Objectives: Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C. Material and Methods: The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis. Results: No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of Streptococcus spp., Enterobacter spp. and Haemophilus spp. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated. Conclusions: PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.