Left ventricular function is related with amphiregulin and fibrosis markers in cirrhotic cardiomyopathy.

The relationship between left ventricle (LV), extracellular matrix remodeling and fibrosis-linked amphiregulin (ARG) in cirrhotic cardiomyopathy (CCM) is unknown. The aim of the study was to investigate the associations between markers of extracellular matrix remodeling and ARG in cirrhosis and their association with indicators of ventricular remodeling and LV functional parameters. In hepatitis C virus (HCV) patients with cirrhosis, who underwent echocardiography, the presence of left ventricular diastolic dysfunction (LVDD) was determined by having gradable diastolic dysfunction in accordance with modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. A total of 87 cirrhotic patients were consecutively analyzed. Based on detailed echocardiographic assessment - 35 HCV patients with cirrhosis had normal left ventricular diastolic function (non-CCM group), whereas 52 patients had LVDD (CCM group). ARG was measured by enzyme-linked immunosorbent assay. The ARG levels were significantly increased in the CCM group compared to the non-CCM group (P<0.001). ARG levels in all HCV patients were independently associated to the presence of CCM, and showed significant correlations with LVDD. The close relationship between ARG levels and the direct serum marker of fibrosis, and selected markers of extracellular matrix (i.e. transforming growth factor-beta1 (TGF-ß1), and carboxyterminal propeptide of type I collagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix proteinase-1 (TIMP-1), respectively), ventricular remodeling (i.e. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-T (hs-TnT)), and LV functional parameters suggest an active role in the myocardial injury. Using ROC analysis, the best marker for the diagnosis of CCM was NT-proBNP with AUROC = 0.796. The area under the curve of ARG (AUROC = 0.709) for predicting CCM was greater than this for PICP (AUROC = 0.662) and similar to this hs-TnT (AUROC = 0.753). The simultaneous monitoring of serum ARG and markers of extracellular matrix and ventricular remodeling can be helpful for the alterations in myocardial function control in HCV patients with cirrhosis.

Serum betatrophin and irisin levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 µg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 µg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 µg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

Serum endocan level in diabetes mellitus of patients with cirrhosis and risk of subsequent development of spontaneous bacterial peritonitis.

The presence of type 2 diabetes mellitus (DM) in patients with cirrhosis is associated with an increased risk of spontaneous bacterial peritonitis (SBP) which may represent an increased susceptibility to infections. Endocan is a key player in the regulation of inflammatory disorders, and a biomarker in bacteremia and sepsis. To investigate the association between both endocan and DM, and developing SBP, we conducted a retrospective cohort study. Three hundred and thirty patients (179 men, 151 women; mean age 61.0 ± 8.5 years) who were treated for liver cirrhosis were studied between January 2007 and December 2016. Univariate and multivariate analyses using age, type 2 diabetes mellitus, severity of cirrhosis (Child-Pugh or MELD score), platelet count, serum proinflammatory cytokines, procalcitonin, C-reactive protein, and endocan level were conducted to identify factors related to the development of SBP. Among 330 patients with the median follow-up of 6.0 years, the cumulative incidence of SBP at 5 years was 28.6%. On multivariate analysis, a high serum endocan level and DM were independent and significant risk factors for SBP development (hazard ratio (HR) 1.634 (95% CI: 1.012 - 2.638; P = 0.047) and 2.482 (95% CI: 1.134 - 5.412; P = 0.023), respectively). Furthermore, the cumulative incidence rate of SBP in cirrhotic patients with high endocan levels was significantly greater than that in patients with low endocan levels (P = 0.035; log-rank test). Endocan is an independent predictor of SBP development in patients with cirrhosis. Cirrhotic patients with type 2 diabetes mellitus who have a higher endocan levels should be monitored carefully for the development of spontaneous bacterial peritonitis.

Increased circulating endocan in patients with cirrhosis: relation to bacterial infection and severity of disease.

Life expectancy of patients with liver cirrhosis is closely linked to the degree of liver dysfunction and the occurrence of bacterial infection. An early diagnosis of infection helps to initiate adequate and timely measures and improves outcome of cirrhotic patients. Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels in cirrhotic patients with bacterial infection and their associations with markers of infection and inflammation. This study sought to assess the diagnostic value of serum levels of endocan, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in 126 patients with cirrhosis: 51 with decompensated infected cirrhosis, 56 with decompensated uninfected and 19 with compensated uninfected cirrhosis at inclusion. We analyzed the association of endocan with clinical factors in cirrhosis by comparison with indicators of infection and inflammation. Endocan, PCT, CRP, IL-6 and TNF-α were assayed in serum samples by ELISA analyses. Serum levels of endocan, PCT, CRP and TNF-α were significantly higher in cirrhotic patients with clinically overt infections. Endocan levels were correlated to neither PCT levels nor IL-6 levels in each group of patients with cirrhosis. CRP and TNF-α levels and Child-Pugh score correlated only in the infected group of patients with endocan levels, while in the uninfected groups of cirrhotic patients no significant correlation could be detected. The diagnostic accuracy of endocan increased in advanced stage of the disease. Serum endocan levels ≥ 2.05 ng/ml had a sensitivity of 76.1% and specificity of 85% for the diagnosis bacterial infection in decompensated cirrhotic patients. The endocan measured at admission is a good clinical parameter predicting the occurrence of infection in these patients. Elevated endocan may reflect the degree of endothelial cell injury induced by a systemic inflammatory response, a pathologic process that could modify the course of advanced cirrhosis.

Oxidatively modified forms of albumin in patients with risk factors of metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a complex metabolic disease connected especially with lipid and carbohydrate disturbances. It is postulated that oxidative stress (OS) is linked to metabolic syndrome, constituting a novel component of its pathogenesis. AIM: We aimed to examine the plasma level of oxidatively modified proteins--advanced oxidation protein products (AOPP) and ischemia modified albumin (IMA)--as well as thiol (SH) groups and evaluate their connection with metabolic agents in relation to MetS prevalence. SUBJECTS AND METHODS: The levels of AOPP, IMA and SH groups were measured spectrophotometrically in 106 patients with MetS risk factors and in 32 control subjects. RESULTS: The levels of examined parameters differed significantly between patients with MetS risk factors and the control group. AOPP significantly correlated with glucose (r = 0.30, p = 0.008), HDL-Ch (r = -0.34, p = 0.005), TG (r = 0.48, p < 0.001) and fibrinogen (r = 0.37, p < 0.001). The levels of AOPP and IMA increased progressively with the number of MetS risk factors, being the most significant for AOPP. The highest values of AOPP were associated with the presence of at least three risk factors. Only AOPP were an independent determinant for MetS occurrence in the studied population (OR = 2.72, p = 0.04). Mutual dependence between metabolic, oxidative stress and inflammatory parameters was revealed. CONCLUSIONS: Oxidative modifications of proteins are increased in MetS and accumulation of MetS risk factors enhances manifestation of OS. AOPP is the most appropriate parameter for determination of OS, with potential diagnostic value in MetS patients.