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• W2022395195 abstract "According to WHO projections, Cirrhosis will be the 9th most common cause of death in the western world by 2015 and the costs of hospital admission owing to complications in the US approximate $13Bn. It is well known that patients with cirrhosis showing signs of decompensation have a higher mortality 1, 2. Several studies tried to define the impact of different clinical features of decompensation on survival 3. When patients are hospitalized, mortality ranges between 44 and 74% 4. This apparently heterogenous outcome can be explained by the fact that it is not the severity of liver disease, but the degree of end-organ failure that determines outcome. The article by Vergara et al. 5 has analysed hospital mortality in patients with cirrhosis in detail. They used registry data from the Administrative Inpatient Dataset of acute-care hospitals collected from 2003 to 2010 and searched for factors associated with mortality. Firstly, they showed that in-hospital mortality of patients with cirrhosis, who are acutely admitted to the hospital, is as high as 11.6%. The mortality, however, decreased remarkably over time during the observation period (27% decrease from 2003–2005 to 2009–2010). This is an encouraging information for hepatologists to further aim for improvement in the management of complications of cirrhosis. The authors conclude that the introduction of specific therapeutic options for complications of cirrhosis (e.g. terlipressin, albumin, cephalosporin) is the main reason for this improvement. It might also be possible that because of high level of awareness among physicians and because of the availability of new diagnostic tests (e.g. noninvasive fibrosis tests), cirrhosis is diagnosed earlier. This has been shown in several other conditions such as cancers, where earlier detection of a disease is associated with better survival rates. In cirrhosis, it is possible that not only the optimized medical care in case of decompensation but also the inclusion of patients into screening programs with optimized medical and supportive care and timely access to liver transplantation improves survival. Vergara et al. 5 identified factors associated with high mortality and found that hepatorenal syndrome carried the highest mortality rate, followed by spontaneous bacterial peritonitis, hepatic encephalopathy, pneumonia and malnutrition. Acute and chronic renal insufficiencies are also listed among the factors increasing mortality; however, it remains questionable how accurate the discrimination between these entities was made by the physicians who entered the data to this database. Another risk factor for mortality was ICU admission. These data are supported by a cohort study that showed a markedly increased 30-day mortality (58%) in cirrhotic inpatients who developed organ failure as compared with those who did not develop organ failure (8%) 6. This underpins again the notion that death in patients with cirrhosis is not related to the severity of underlying liver disease, but related to the development of organ failure 6. A closer look towards the factors associated with mortality leads to the hypothesis that infection and/or inflammation might play an important role in all these conditions. Two specific infections – spontaneous bacterial peritonitis and pneumonia – are among the top 5 factors. For hepatic encephalopathy, a synergistic role of inflammation in the development of brain failure has been well described 7. In hepatorenal syndrome, bacterial translocation and proinflammatory cytokines are important pathogenetic factors 8 and the systemic inflammatory response syndrome (SIRS) is frequently associated with hepatorenal syndrome 9, 10. Also in chronic kidney disease, the role of inflammation has been well established 11, 12. Malnutrition is known to be associated with an increased mortality in liver disease – in the present study by Vergara et al. 5, the odds ratio for death in patients with malnutrition was 6.2, which was the second highest odds ratio in this study. Therefore, patients with malnutrition in this study had a hospital mortality of 43.1%, which is terribly high. Malnutrition can lead to increased gut permeability 13, which consequently leads to an increased systemic endotoxaemia 14, which in turn can cause immune dysfunction and increases the risk of infection 15. As cirrhosis itself also increases gut permeability and endotoxaemia 16, this common pathway of inflammation, leading to immune dysfunction 17 and causing complications of cirrhosis seems to be a promising target for novel therapeutic strategies such as modulation of gut flora and/or permeability by probiotics. The role of inflammation and infection is also underpinned by recent data: the CANONIC study 18 was able to define ACLF as a distinct syndrome associated with an exaggerated inflammatory response related to bacterial infections, alcoholic liver injury or other yet unidentified factors and the newly developed CLIF score predicts mortality accurately. It is striking that the same variables, such as renal failure and hepatic encephalopathy, were predictive for mortality in the present study by Vergara et al. 5 and in the CANONIC study. Finally, Vergara et al. 5 found gender differences in mortality rates. As expected, there was a male predominance, however, above the age of 74, this difference disappears. Mortality increases with age in both male and female, reflecting differences in aetiology and natural history of the disease between men and women. This study helps to understand from which complications patients with cirrhosis die. Therefore, it can be used to generate new prognosis models to identify patients at risk and also develop novel therapeutic strategies to tackle the problem of inflammation as a common pathway of many complications of cirrhosis. Furthermore, this study is encouraging because it shows us that standard of care improved over the last decade in cirrhosis and supports us to do even better in the next decade." @default.
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• W2022395195 date "2013-06-09" @default.
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• W2022395195 title "Hospital mortality of cirrhosis: better, but still room for improvement!" @default.
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• W2022395195 doi "https://doi.org/10.1111/liv.12166" @default.
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