title: Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: A prospective study.
abstract: OBJECTIVE
  To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis.
  
  
  METHODS
  IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.
  
  
  RESULTS
  Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.
  
  
  CONCLUSIONS
  Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.
authors.affiliation: Anika Vogt, Philipp A Reuken, Sven Stengel, Andreas Stallmach, Tony Bruns, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Anika Vogt, Philipp A Reuken, Sven Stengel, Andreas Stallmach, Tony Bruns, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Reuken
authors.affiliation: Anika Vogt, Philipp A Reuken, Sven Stengel, Andreas Stallmach, Tony Bruns, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Stengel
authors.affiliation: Anika Vogt, Philipp A Reuken, Sven Stengel, Andreas Stallmach, Tony Bruns, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stallmach
authors.affiliation: Anika Vogt, Philipp A Reuken, Sven Stengel, Andreas Stallmach, Tony Bruns, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Tony
authors.initials: T
authors.lastname: Bruns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality; D018988:Bacterial Translocation; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D000069196:Gastrointestinal Microbiome; D006760:Hospitalization; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007421:Intestine, Small / Q000378:metabolism* / Q000382:microbiology; D053208:Kaplan-Meier Estimate; D007792:Lactulose / Q000378:metabolism*; D016014:Linear Models; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D008297:Male; D008353:Mannitol / Q000378:metabolism*; D008875:Middle Aged; D010538:Peritonitis / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality; D010539:Permeability; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D008353:Mannitol; D007792:Lactulose
keywords: Bacterial translocation; Intestinal permeability; Lactulose/mannitol ratio; Liver cirrhosis; Spontaneous bacterial peritonitis