Anatol Panasiuk

Liver fibrosis markers in alcoholic liver disease

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

The effect of the severity of liver cirrhosis on the level of lipids and lipoproteins

The effect of severity of liver cirrhosis, an alcoholic and non-alcoholic genesis, on the results of serum lipids and lipoproteins was evaluated. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-Ch), and low-density lipoprotein cholesterol (LDL-Ch) were measured in the sera of 59 patients suffering from alcoholic cirrhosis and 34 patients with non-alcoholic cirrhosis. The level of serum triglycerides depends on the severity of liver damage in alcoholic liver cirrhosis, being the highest in Child-Pugh score B. The severity of liver damage significantly affects the HDL-Ch and LDL-Ch levels in cirrhosis of non-alcoholic origin, reaching the highest value for LDL-Ch and the lowest for HDL-Ch in score C. It should not be generalized that the levels of lipids and lipoproteins in liver cirrhosis progressively diminished with the deterioration of liver function. The serum HDL-Ch and LDL-Ch may be considered as markers of severity of liver damage in non-alcoholic cirrhosis, but the triglycerides only in disease of alcoholic origin.

Association among Fas expression in leucocytes, serum Fas and Fas-ligand concentrations and hepatic inflammation and fibrosis in chronic hepatitis C.

Background: Replication of the hepatitis C virus (HCV) in peripheral blood mononuclear cells (PBMC) may impair immune functions and establish persistent infection. The aim of this study was to assess the influence of HCV on PBMC and their susceptibility to apoptosis in relation to liver inflammation and fibrosis.

Increase in expression of monocytic tissue factor (CD142) with monocytes and blood platelet activation in liver cirrhosis.

Tissue factor (TF) is one of the proteins that participate in hemostatic and inflammatory processes. Activated monocytes present in the liver increase expression of TF, and while accumulating in the organ they can intensify inflammation. The aim of the present study was to evaluate the expression of TF on monocytes in advanced liver cirrhosis with regard to other activation markers. The flow cytometric analysis of TF (CD142), CD14, adhesive molecules CD11b and CD11c, costimulatory molecules CD40, CD80 and CD86, and HLA-DR+ on monocytes was carried out in 45 patients with postalcoholic liver cirrhosis (Child Pugh B, 20 patients; Child Pugh C, 25 patients) and in 25 healthy persons. The positive correlation between monocytic TF expression and monocyte [soluble CD14 (sCD14), CD11b, monocyte aggregates] activation, the expression of costimulatory molecules on monocytes (CD40, CD80), blood platelet (soluble P-selectin, microplatelets) activation, the level of tumor necrosis factor-α, biochemical parameters of liver damage (alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, γ-glutamyltransferase, and bilirubin) as well as coagulation disorders were observed in the study. In conclusion, the study revealed that the activation of monocytes and blood platelets is accompanied by the elevation of monocytic TF expression in advanced liver cirrhosis. The monocytic TF is a significant link connecting clotting processes and inflammatory and immunological phenomena in liver cirrhosis.

Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C.

Cytochrome c (CYC) and M30‐neoepitope of cytokeratin‐18 (M30‐CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30‐CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC).

Total and Free Serum Sialic Acid Concentration in Liver Diseases

Background. The objective of this study was to compare the levels of total (TSA) and free (FSA) sialic acid in acute and chronic liver diseases. Materials and Methods. The serum TSA and FSA levels were determined in 278 patients suffering from acute and chronic liver diseases of different etiologies. TSA was estimated by enzymatic method and FSA by the thiobarbituric method modified by Skoza and Mohos. Results. There were no significant differences in the serum TSA concentration between liver diseases of different etiologies, although in most of the liver diseases the mean TSA level was significantly lower than that in the control group. In contrast to TSA, the concentration of FSA appears to differ between liver diseases. In toxic hepatitis it was higher than that in nonalcoholic cirrhosis. However, neither of them differs between alcoholic and nonalcoholic cirrhosis or between liver tumors and tumors with cirrhosis. Conclusions. We conclude that the changes in concentrations of TSA and FSA during the same liver diseases indicate significant disturbances in sialylation of serum glycoproteins.

Serum total and free sialic acid in patients with chronic liver disease

Sialic acid (SA) is a derivative of neuraminic acid attached to the carbohydrate chains of glycoproteins and glycolipids. The attachment of SA to carbohydrate chains takes place in the liver. Therefore, it has been hypothesized that liver function influences serum SA concentrations. Variations in serum total SA (TSA) concentrations in chronic liver diseases such as cirrhosis, hepatoma, viral hepatitis and fatty liver were reported previously, but there are differences in published results (1–3). Additionally, post-translational glycosylation (sialylation) of proteins in the liver is affected by chronic alcohol abuse (4–6). These perturbations cause the release of the free form of SA (FSA) and increase its concentration in the sera of alcoholics (7). This study compares serum TSA and FSA concentrations in patients suffering from cirrhosis and viral hepatitis. The test group consisted of 79 patients (27 females and 52 males) (mean age: 55 years; range: 20–84). The patients were divided into three subgroups: alcoholic cirrhosis – 31 patients (12 females and 19 males), non-alcoholic cirrhosis – 24 patients (9 females and 15 males) and chronic viral hepatitis C – 24 patients (10 females and 14 males). Causes of non-alcoholic liver cirrhosis were hepatitis B (7 cases) and C virus (3 cases), biliary obstruction (5 cases), autoimmune hepatitis (5 cases) and steatohepatitis (4 cases). Diagnosis was on the basis of physical and clinical examination (abdominal ultrasound, microscopic analysis of liver biopsy samples in selected cases), serological testing whepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV)x and biochemical evidence of liver damage. The control group consisted of 49 healthy subjects recruited from

Serum Sialic Acids Levels According to the Severity of Liver Cirrhosis

The sialylation of serum proteins and lipids changes in liver diseases of different etiologies and could change the total sialic acid (TSA), lipid‐bound SA (LSA), and free SA (FSA) levels in the sera. However, little is known of the relationship of serum SAs concentrations and the severity of liver disease. Therefore, the aim of this study was to investigate the SAs concentrations (TSA, LSA, and FSA) in liver cirrhosis in relation with the severity of liver disease.

N-Latex CDT Results in Liver Diseases

AIMS The aim of this study was to test whether liver diseases of alcoholic and non-alcoholic origin cause false-positive carbohydrate-deficient transferrin (CDT) results when the particle-enhanced immunonephelometry for CDT assays is used and to assess the effect of liver disease severity on N-Latex CDT results. METHODS Blood was sampled from 245 newly admitted patients suffering from liver diseases: alcoholic and non-alcoholic cirrhosis (AC), chronic viral (B and C) and non-viral hepatitis, toxic and autoimmune hepatitis (AIH), hepatocellular carcinoma and primary biliary cirrhosis (PBC). CDT was determined by particle-enhanced imunononephelometry using the N-Latex CDT test. RESULTS There were significant differences in %CDT levels between liver diseases of various etiologies. The %CDT level in AC was higher than that in chronic hepatitis (non-viral and viral C). In turn, the %CDT level in chronic hepatitis C was lower than that in toxic hepatitis. The frequency of false-positive %CDT results in liver diseases of non-alcoholic origin was 13/146, and was highest in AIH (4/14). There were no CDT-positive results in PBC and chronic hepatitis B. The frequency of CDT-positive results in alcoholic liver diseases was 24/59 in cirrhosis and 10/34 in hepatitis. Serum levels of %CDT in cirrhotic patients are correlated with the severity of the disease assessed by the Child-Pugh score. CONCLUSION We concluded that the liver diseases affect the relative but not absolute values of CDT when using the assay with the monoclonal antibodies directed against CDT. The CDT results from N-Latex CDT test reflect the severity of liver dysfunction.

Hyaluronic acid concentration in liver diseases

The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn’s index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)—57 patients, non-alcoholic cirrhosis (NAC)—30 and toxic hepatitis (HT)—22. Cirrhotic patients were classified according to Child–Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child–Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.