Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

High risk of delisting or death in liver transplant candidates following infections: Results from the North American Consortium for the Study of End-Stage Liver Disease.

Because Model for End-Stage Liver Disease (MELD) scores at the time of liver transplantation (LT) increase nationwide, patients are at an increased risk for delisting by becoming too sick or dying while awaiting transplantation. We quantified the risk and defined the predictors of delisting or death in patients with cirrhosis hospitalized with an infection. North American Consortium for the Study of End-Stage Liver Disease (NACSELD) is a 15-center consortium of tertiary-care hepatology centers that prospectively enroll and collect data on infected patients with cirrhosis. Of the 413 patients evaluated, 136 were listed for LT. The listed patients' median age was 55.18 years, 58% were male, and 47% were hepatitis C virus infected, with a mean MELD score of 2303. At 6-month follow-up, 42% (57/136) of patients were delisted/died, 35% (47/136) underwent transplantation, and 24% (32/136) remained listed for transplant. The frequency and types of infection were similar among all 3 groups. MELD scores were highest in those who were delisted/died and were lowest in those remaining listed (25.07, 24.26, 17.59, respectively; P < 0.001). Those who were delisted or died, rather than those who underwent transplantation or were awaiting transplantation, had the highest proportion of 3 or 4 organ failures at hospitalization versus those transplanted or those continuing to await LT (38%, 11%, and 3%, respectively; P = 0.004). For those who were delisted or died, underwent transplantation, or were awaiting transplantation, organ failures were dominated by respiratory (41%, 17%, and 3%, respectively; P < 0.001) and circulatory failures (42%, 16%, and 3%, respectively; P < 0.001). LT-listed patients with end-stage liver disease and infection have a 42% risk of delisting/death within a 6-month period following an admission. The number of organ failures was highly predictive of the risk for delisting/death. Strategies focusing on prevention of infections and extrahepatic organ failure in listed patients with cirrhosis are required.

Hyponatremia in cirrhosis: Results of a patient population survey.

Low serum sodium concentration is an independent predictor of mortality in patients with cirrhosis, but its prevalence and clinical significance is unclear. To evaluate prospectively the prevalence of low serum sodium concentration and the association between serum sodium levels and severity of ascites and complications of cirrhosis, prospective data were collected on 997 consecutive patients from 28 centers in Europe, North and South America, and Asia for a period of 28 days. The prevalence of low serum sodium concentration as defined by a serum sodium concentration < or =135 mmol/L, < or =130 mmol/L, < or =125 mmol/L, and < or =120 mmol/L was 49.4%, 21.6%, 5.7%, and 1.2%, respectively. The prevalence of low serum sodium levels (<135 mmol/L) was high in both inpatients and outpatients (57% and 40%, respectively). The existence of serum sodium <135 mmol/L was associated with severe ascites, as indicated by high prevalence of refractory ascites, large fluid accumulation rate, frequent use of large-volume paracentesis, and impaired renal function, compared with normal serum sodium levels. Moreover, low serum sodium levels were also associated with greater frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome, but not gastrointestinal bleeding. Patients with serum sodium <130 mmol/L had the greatest frequency of these complications, but the frequency was also increased in patients with mild reduction in serum sodium levels (131-135 mmol/L). In conclusion, low serum sodium levels in cirrhosis are associated with severe ascites and high frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome.

The use of TIPS in chronic liver disease.

The development of cirrhosis and portal hypertension in the natural history of chronic liver disease is associated with many complications. A transjugular intrahepatic portosystemic stent shunt (TIPS) is a metal prosthesis that has been shown to be very effective in lowering sinusoidal portal pressure, and therefore is effective in the management of complications of cirrhosis, especially those related to portal hypertensive bleeding and sodium and water retention. In patients with acute variceal bleeding not responding to pharmacologic and endoscopic treatments, a reduction of the hepatic venous pressure gradient to < 12 mmHg or by > 20% with TIPS has been shown to be effective in controlling the acute bleed and in preventing rebleeding. For stable patients whose acute variceal bleed is controlled, TIPS is equal to combined beta-blocker and band ligation in the prevention of recurrent variceal bleed. TIPS is also more effective than large volume paracentesis in the control of refractory ascites, and may confer a survival advantage over repeated large volume paracentesis. TIPS has also been used in the management of other complications related to portal hypertension including ectopic varices, hepatic hydrothorax, and hepatorenal syndrome with some success, but experience is still rather limited. Miscellaneous uses include treatment of Budd Chiari Syndrome, portal hypertensive gastropathy and hepatopulmonary syndrome. Careful patient selection is vital to a successful outcome, as patients with severe liver dysfunction tend to die post-TIPS despite a functioning shunt. All patients who require a TIPS for treatment of complications of cirrhosis should be referred for consideration of liver transplant.