701 Mannose-Binding Lectin Deficiency Confers Risk for Bacterial Infections in a Large Hungarian Cohort of Patients With Liver Cirrhosis
ABSTRACT Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state.
Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients.
MBL level and the prevalence of absolute MBL deficiency (<100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03).
MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.
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- "Indeed, ascites due to cirrhosis increases susceptibility to bacterial infection, and this has been related to low opsonic activity as a result of reduced concentrations of C3, C4 and CH50 in serum and ascitic fluid  . The defensive relevance of PRRs synthesized by the liver is also highlighted by the fact that cirrhotic patients with a gene polymorphism conferring them low serum levels of the recognition molecule mannose binding lectin, or transplant recipients of a liver with this polymorphism, show an increased risk of bacterial infection  . "
ABSTRACT: The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this constitutes the pathophysiological hallmark of an increased susceptibility to bacterial infection, distinctive of the disease. Cirrhosis impairs the homeostatic role of the liver in the systemic immune response. Damage to the reticulo-endothelial system compromises the immune surveillance function of the organ and the reduced hepatic synthesis of proteins, involved in innate immunity and pattern recognition, hinders the bactericidal ability of phagocytic cells. Systemic inflammation, in form of activated circulating immune cells and increased serum levels of pro-inflammatory cytokines, is the result of persistent episodic activation of circulating immune cells from damage-associated molecular patterns, released from necrotic liver cells and, as cirrhosis progresses, from pathogen-associated molecular patterns, released from the leaky gut. Cirrhosis-associated immune dysfunction phenotypes switch from predominantly “pro-inflammatory” to predominantly “immunodeficient” in patients with stable ascitic cirrhosis and in patients with severely decompensated cirrhosis and extra-hepatic organ failure (e.g. acute-on-chronic liver failure), respectively. These cirrhosis-associated immune dysfunction phenotypes represent the extremes of a spectrum of reversible dynamic events that take place during the course of cirrhosis. Systemic inflammation can affect the functions of tissue somatic cells and modify the clinical manifestation of cirrhosis. The best characterized example is the contribution of systemic inflammation to the haemodynamic derangement of cirrhosis, which correlates negatively with prognosis.Journal of Hepatology 12/2014; 61(6). DOI:10.1016/j.jhep.2014.08.010 · 10.40 Impact Factor
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- "Cirrhotic patients carrying NOD2 (nucleotide-binding oligomerization domain containing 2) variants associated with impairment of recognition of bacterial product muramyl dipeptide have a higher risk of SBP and a reduced survival time . Mannose-binding lectin deficiency, inducing a defect in opsonophagocytosis of bacteria, confers a higher risk of bacterial infections in patients with cirrhosis . Toll-like receptor (TLR)2 polymorphisms are also associated with an increased susceptibility towards SBP . "
ABSTRACT: Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C-reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population.Journal of Hepatology 01/2012; 56 Suppl 1:S1-12. DOI:10.1016/S0168-8278(12)60002-6 · 10.40 Impact Factor
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ABSTRACT: Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. Sera of 676 patients with various chronic liver diseases (autoimmune diseases: 266, viral hepatitis C: 124, and liver cirrhosis of different etiology: 286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae (ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR: 1.62, 95%CI: 1.16-2.25), co-morbidities (OR: 2.22, 95%CI: 1.27-3.86), and ASCA positivity (OR: 1.59, 95%CI: 1.07-2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR: 1.85) and co-morbidities (p<0.001, OR: 2.02) by Cox-regression analysis. The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.PLoS ONE 09/2010; 5(9):e12957. DOI:10.1371/journal.pone.0012957 · 3.23 Impact Factor