Alterations In Liver Diseases Research Articles

High serum N-terminal propeptide of procollagen type III concentration is associated with liver diseases.

IntroductionN-terminal propeptide of procollagen type III (PIIINP) is generated during the synthesis of type III collagen. PIIINP can be measured in the serum as an indicator of liver fibrosis and cirrhosis.AimTo evaluate the effect of liver diseases of different aetiologies and clinical severity of liver cirrhosis on the serum level of PIIINP.Material and methodsPatients with alcoholic cirrhosis (AC) – 63 subjects, non-alcoholic cirrhosis (NAC) – 31 and toxic hepatitis (HT) – 33 were studied. Cirrhotic patients were classified according to the Child-Pugh scale. The samples were analysed using the ELISA method.ResultsThe level of PIIINP was significantly higher in patients with alcoholic cirrhosis, non-alcoholic cirrhosis, and toxic hepatitis in comparison to the control group. There were no significant differences in the serum PIIINP levels between liver diseases and according to the severity of liver cirrhosis. PIIINP has the highest diagnostic power for the diagnosis of toxic hepatitis. The highest sensitivity was reached in alcoholic cirrhosis, but other diagnostic values (specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy (ACC)) in alcoholic cirrhosis were lower than that in toxic hepatitis. In the diagnosis of non-alcoholic cirrhosis PIIINP has low sensitivity, specificity, PPV, NPV, and ACC.ConclusionsThe serum PIIINP shows the alterations in liver diseases in comparison to healthy controls, but not between diseases. Taking the above into account we can suggest that PIIINP may be a useful test for the detection of liver diseases.

Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue.

It is well known that isolation and cultivation of primary hepatocytes cause major gene expression alterations. In the present genome-wide, time-resolved study of cultivated human and mouse hepatocytes, we made the observation that expression changes in culture strongly resemble alterations in liver diseases. Hepatocytes of both species were cultivated in collagen sandwich and in monolayer conditions. Genome-wide data were also obtained from human NAFLD, cirrhosis, HCC and hepatitis B virus-infected tissue as well as mouse livers after partial hepatectomy, CCl4 intoxication, obesity, HCC and LPS. A strong similarity between cultivation and disease-induced expression alterations was observed. For example, expression changes in hepatocytes induced by 1-day cultivation and 1-day CCl4 exposure in vivo correlated with R = 0.615 (p < 0.001). Interspecies comparison identified predominantly similar responses in human and mouse hepatocytes but also a set of genes that responded differently. Unsupervised clustering of altered genes identified three main clusters: (1) downregulated genes corresponding to mature liver functions, (2) upregulation of an inflammation/RNA processing cluster and (3) upregulated migration/cell cycle-associated genes. Gene regulatory network analysis highlights overrepresented and deregulated HNF4 and CAR (Cluster 1), Krüppel-like factors MafF and ELK1 (Cluster 2) as well as ETF (Cluster 3) among the interspecies conserved key regulators of expression changes. Interventions ameliorating but not abrogating cultivation-induced responses include removal of non-parenchymal cells, generation of the hepatocytes’ own matrix in spheroids, supplementation with bile salts and siRNA-mediated suppression of key transcription factors. In conclusion, this study shows that gene regulatory network alterations of cultivated hepatocytes resemble those of inflammatory liver diseases and should therefore be considered and exploited as disease models.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1761-4) contains supplementary material, which is available to authorized users.

Protein and site specificity of fucosylation in liver-secreted glycoproteins.

Chronic liver diseases are a serious health problem worldwide. One of the frequently reported glycan alterations in liver disease is aberrant fucosylation, which was suggested as a marker for noninvasive serologic monitoring. We present a case study that compares site specific glycoforms of four proteins including haptoglobin, complement factor H, kininogen-1, and hemopexin isolated from the same patient. Our exoglycosidase-assisted LC–MS/MS analysis confirms the high degree of fucosylation of some of the proteins but shows that microheterogeneity is protein- and site-specific. MSn analysis of permethylated detached glycans confirms the presence of LeY glycoforms on haptoglobin, which cannot be detected in hemopexin or complement factor H; all three proteins carry Lewis and H epitopes. Core fucosylation is detectable in only trace amounts in haptoglobin but with confidence on hemopexin and complement factor H, where core fucosylation of the bi-antennary glycans on select glycopeptides reaches 15–20% intensity. These protein-specific differences in fucosylation, observed in proteins isolated from the same patient source, suggest that factors other than up-regulation of enzymatic activity regulate the microheterogeneity of glycoforms. This has implications for selection of candidate proteins for disease monitoring and suggests that site-specific glycoforms have structural determinants, which could lead to functional consequences for specific subsets of proteins or their domains.

Haemostatic alterations in liver diseases

Background - The liver is the major site of synthesis for all the clotting factors. The concentrations of these factors, especially factor V has been demonstrated to fall proportionately to the increasing severity of the disease. Liver disease also leads to vitamin K deficiency, mainly by the decreased absorption from the gut due to the reduced bile salts secretion from the liver. The physiology of the hemostatic system is closely linked to liver function because the liver parenchymal cells produce most of the factors of clotting and fibrinolytic systems and because the liver regulates the activation or inhibition of both systems. Objectives - The present study is designed to assess the values of various haemostatic parameters in liver disease. Results and Conclusions - On comparing the mean prothrombin time, activated partial thromboplastin time (APTT), thrombin time, and mean fibrinogen level in cases of liver disease with that in the controls, it was found to be significantly (p<0.001) increased in liver disease.

Electrolyte Alterations in Liver Disease and Hepatic Coma

Electrolyte Alterations in Liver Disease and Hepatic Coma

Serum glutamic oxalacetic aminopherase (transaminase) in hepatitis.

Glutamic oxalacetic aminopherase (transaminase) is widely distributed in animal tissues. Its greatest activity has been found in homogenates of heart muscle, skeletal muscle, brain, liver, and kidney, in decreasing order. This enzyme activity has been found in all animal and human serums tested, and the activities are comparable whether the analysis is done chromatographically or spectrophotometrically. It has been demonstrated that serum glutamic oxalacetic aminopherase activity increases 2 to 20 times normal after acute myocardial infarction and may rise 20 to 100 times normal in hepatitis due to toxic or infectious agents. The present study is an extension of a preliminary report on serum glutamic oxalacetic aminopherase alterations in liver disease, with particular emphasis on hepatitis. The study to be reported will describe the activity in hepatitis and discuss the usefulness of determination of the activity in the diagnosis and management of hepatitis and in the epidemiological course of infectious