Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.

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C-reactive protein on its own is a sensitive screening test for the presence of bacterial infections in cirrhosis and is also a useful marker to predict the likelihood of clinically significant bacterial infections in patients without overt infections.

Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.

PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.

BackgroundBacterial 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.Methodology/Principal FindingsSera 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.Conclusions/SignificanceThe 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.

Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contractile responsiveness to physical, physiological and pharmacological stress. Importantly, cardiac dysfunction can be reversible and can improve due to effective medical treatment and also after liver transplantation. Echocardiography and electrocardiography are essential tools for recognizing the characteristic changes in the myocardial function and also the alterations in the electrophysiological properties of the heart. Laboratory markers are auxiliary modalities further aiding the establishment of the correct diagnosis. In this review, we aimed to collect the pathophysiological background and clinical characteristics of CCM with the intention of summarizing the current possibilities for the diagnosis establishment and treatment of this cardio-hepatic disorder.Abbreviations: A: late diastolic transmitral peak flow velocity; ACE: angiotensin converting enzyme; ANP: atrial natriuretic peptide; ARB: angiotensin receptor blocker; BNP: brain natriuretic peptide; cAMP: cyclic adenosine monophosphate; CCM: cirrhotic cardiomyopathy; CGRP: calcitonin gene-related peptide; CO: carbon monoxide; DD: diastolic dysfunction; DT: deceleration time; E: early diastolic transmitral peak flow velocity; Ea: early diastolic velocity of the septal mitral annulus; EF: ejection fraction; MUGA: Multi Gated Acquisition Scan; NO: nitric oxide; NSBB: non-selective beta-blocker; pro-BNP: pro-brain natriuretic peptide; QTc: corrected QT interval; RAAS: renin-angiotensin aldosterone system; RALES: Randomized Aldactone Evaluation Study; suPAR: urokinase-type plasminogen activator receptor; TDI: Tissue Doppler Imaging; TIPS: transjugular intrahepatic portosystemic shunt; TNF-alpha: tumor necrosis factor-alpha.

AIMTo assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients.METHODSSera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls.RESULTSA total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level.CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.