Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylated- interferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-alpha 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.
 ...
PMID:Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C. 1693 80

Gene silencing through aberrant CpG island methylation is a frequent epigenetic defect in hepatocellular carcinoma (HCC). However, nothing is known as yet whether aberrant hypermethylation occurs already in non-neoplastic liver cells from patients with hereditary haemochromatosis who have a clearly elevated risk for developing HCC. Therefore, quantitative real-time PCR-based methylation analysis of six genes frequently hypermethylated in HCC (RASSF1A, cyclinD2, p16(INK4a), GSTpi1, SOCS-1, APC) was performed for liver biopsies from patients with hereditary haemochromatosis. For genotyping of the HFE gene restriction enzyme analysis and Pyrosequencing were used. Transcriptional repression of hypermethylated genes was assessed using real-time RT-PCR. Eighty-four percent of all samples with severe hepatic iron overload and a mutated HFE gene (but without HCC) had at least one gene hypermethylated. All six genes tested were affected by aberrant hypermethylation, albeit to a different extent: RASSF1A 55%, cyclinD2 45%, p16(INK4a) 32%, GSTpi1 10%, SOCS-1 6%, APC 8%. Concomitant transcriptional down-regulation was shown for RASSF1A, cyclinD2, GSTpi1 and SOCS-1. Biopsies from haemochromatosis patients showed significantly more aberrant hypermethylation than normal liver tissue or benign liver tumours (P < 0.001) and also to a higher degree. This effect is independent of patient age, cirrhosis or hepatitis infection. This is the first report demonstrating that longstanding severe iron overload is frequently associated with epigenetic defects characteristic of HCC, which reflects the increased risk of these lesions to progress to HCC. Thus, changes in DNA methylation patterns are an early event preceding morphological alterations of malignant transformation and represent promising targets for early detection.
 ...
PMID:Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis. 1741 60

The purpose of the investigation was to study the condition of the protein C system in chronic virial hepatitis (CVH) and viral hepatic cirrhosis (HC) during the course of antiviral therapy. The total protein C system activity (in a form of normalized ratio - NR) was studied before and 6 month after antiviral therapy in 27 patients with CVH B, in 79 patients with CVH C, and in 5 patients CVH D, as well in 29 patients with viral HC and 29 patients with alcoholic HC/. The total protein C system activity was decreased in chronic viral hepatic disease, and was minimal in patients with HC; the most severe disturbances were observed in patients with poor prognosis of HC and decompensated portal hypertension. The study found a correlation between NR values and histological manifestation of the pathology, which demonstrates an important role of the protein C system in the progress of chronic hepatic diseases. Anti-virial drugs had a positive effect of the functioning of the protein C system, which may be one of the ways of the realization of their antifibrotic effect.
 ...
PMID:[The protein C system in chronic hepatic diseases, and anti-viral therapy]. 1836 97

To investigate whether aberrant hypermethylation in plasma DNA could be used as diagnosis makers for hepatocellular carcinoma (HCC), we performed methylation-specific PCR (MSP) to check the methylation status of five tumor associated genes in 36 cases of tissue and 42 cases of plasma samples from HCC and liver cirrhosis patients, respectively. The hypermethylation frequency of GSTP1 and RASSF1A showed significant difference between HCCs and liver cirrhosis with or without HBV infection (P<0.05), but differences of the hypermethylation status of APC, E-cadherin, and P16 were not statistically significant. There were no significant differences in the hypermethylation status of five genes between the groups of cirrhosis with and without HBV infection. The significant differences of E-cadherin, GSTP1, P16, and RASSF1A in methylation between HCCs and liver cirrhosis were not observed in the plasma samples. Furthermore, the inconsistent results of MSP and real-time quantitative PCR for the paired samples of tissue and plasma suggested that plasma DNA could not fully stand for tissue DNA. In conclusion, hypermethylation of some specific, but not all, tumor associated genes may be involved in hepatocarcinogenesis; examination of the methylation status of E-cadherin, GSTP1, P16, and RASSF1A in the plasma samples might have limited usage for HCC diagnosis.
 ...
PMID:Methylation of tumor associated genes in tissue and plasma samples from liver disease patients. 1869 70

Observations that hepatic inflammation and cirrhosis are associated with the presence of thrombi within the hepatic microvasculature and fibrin-fibrinogen deposition have led to epidemiologic studies showing that carriage of the factor V Leiden mutation, protein C deficiency, and increased expression of factor VIII are associated with rapid progression to cirrhosis in a chronic hepatitis C virus. Additional data suggest that this process may extend more broadly to progression in many forms of chronic liver disease. This article discusses the evidence for a role for coagulation cascade activity in hepatic fibrogenesis and explores the proposed pathogenic mechanisms including the downstream events of thrombin activation. Interference with either the generation of thrombin or its downstream activity may reduce hepatic fibrosis. Also examined are the implications for future therapeutic intervention.
 ...
PMID:Parenchymal extinction: coagulation and hepatic fibrogenesis. 1915 Mar 16

Liver disease has been associated with abnormalities in haemostasis. In this study, coagulation times, platelet counts, platelet activity parameters, activities of individual coagulation factors, D-dimers, antithrombin (AT) and protein C activity were measured in 42 dogs with histologically confirmed liver disease. Outcome was correlated with histological diagnosis. One or more coagulation abnormalities were present in 57% of dogs with hepatic disease. Activated partial thromboplastin time was significantly prolonged in dogs with chronic hepatitis (CH), with or without cirrhosis. Mean platelet numbers, AT and factor IX activity were significantly lower in dogs with CH plus cirrhosis, compared to dogs with other hepatopathies. D-dimers were not significantly increased in any group. Only three dogs, all with different histological diagnoses, satisfied the criteria for disseminated intravascular coagulation (DIC). Haemostatic abnormalities were primarily seen in dogs with cirrhosis and this may be due to reduced synthesis rather than increased consumption of coagulation factors.
 ...
PMID:Coagulation disorders in dogs with hepatic disease. 1948 41

Acquired coagulation defects are characterized by a decrease of both pro- and anti-coagulants. Because of this, we hypothesise that global tests, such as the prothrombin and partial thromboplastin times (PT and APTT), might be unsuitable for their investigation. Indeed, these tests are not good predictors of bleeding in acquired coagulopathies as they are in the congenital ones. This article discusses the possible reasons for this, using cirrhosis and the neonatal period as epitomes of acquired coagulation defects. Both display normal thrombin generation in the presence of thrombomodulin, in spite of prolonged PT and APTT. We surmise that, because of their design, the PT and APTT are responsive to thrombin generated as a function of pro-coagulants, but much less to thrombin inhibited by the anti-coagulants, especially protein C, which is activated to a limited extent in the absence of thrombomodulin. In conclusion, the PT and APTT can tell us whether or not a patient is deficient in one or more pro-coagulants, but not whether this deficiency is counterbalanced by a parallel deficiency of anti-coagulants. Thrombin generation assays are more suitable than PT and APTT for use in acquired coagulation defects.
 ...
PMID:Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. 1965 48

Gastric antral vascular ectasia (GAVE) and radiation proctitis are two vascular disorders of the gastrointestinal tract that typically present with recurrent gastrointestinal bleeding. Although the pathogenesis of either condition is not known, they are unlikely to be similar. GAVE appears to be related to autoimmune disorders or cirrhosis, while radiation proctitis is the result of pelvic irradiation, most commonly used for the treatment of pelvic malignancies. Medical therapies for both conditions are not typically effective, and surgical therapies are usually not required because endoscopic treatment, aimed at coagulation of the underlying vascular lesions, has evolved as the most effective therapy. There is limited evidence in the literature for the use of medical and surgical therapies, with most of the evidence coming from case reports involving small numbers of patients. In the present article, we review the evidence for the use of argon plasma photocoagulation (APC, the most commonly used endoscopic modality) in the treatment of GAVE and radiation proctitis.
 ...
PMID:Argon photocoagulation in the treatment of gastric antral vascular ectasia and radiation proctitis. 2001 31

Protein S (PS), protein C (PC), and antithrombin (AT) are produced by the liver, and their levels were previously shown to be reduced in chronic as well as acute liver disease. The aim of this study was to determine whether measurement of PS, PC, and AT levels in patients would be as good as the commonly used clinical and histological parameters of liver disease in discriminating early and advanced hepatocyte dysfunction. A total of 154 patients were recruited and categorized into five groups: hepatitis B inactive carriers in group 1 (n = 29), nonalcoholic steatohepatitis patients in group 2 (n = 30), chronic hepatitis B patients with elevated liver enzymes in group 3 (n = 29), chronic hepatitis C patients with elevated liver enzymes in group 4 (n = 30), liver cirrhosis patients in group 5 (n = 36). There were significant differences between groups in the levels of PC (P = 0.0001), total PS (P = 0.0001), and free PS (P = 0.0001) and AT (P = 0.0001). These parameters were least affected in the control group, then groups 1 and 2, followed by groups 3 and 4, and most affected in group 5. No differences in these tests were detected between groups 1 and 2 and between groups 3 and 4. Univariate and multivariate analyses showed that free PS was the only predictor of significant inflammation (P = 0.0001), and AT (P = 0.001) and PC (P = 0.003) were the most important factors associated with advanced fibrosis. Both PS and PC are sensitive markers of liver disease, but PS is a sensitive marker of liver inflammation, whereas PC may be a more sensitive marker for liver fibrosis.
 ...
PMID:Natural anticoagulants can be useful predictors of severity in chronic liver disease. 2001 98

Portal vein thromboses are frequent in cirrhotic patients and may be favoured by hypercoagulability in the splanchnic venous system. The coagulation balance and thrombin generation (TG) were evaluated in platelet-free plasma obtained from portal and systemic blood samples in 28 cirrhotic patients while undergoing transjugular intrahepatic porto-systemic shunt. TG assay (TGA) was performed with all samples from cirrhotic patients and with plasma samples from 14 healthy controls, with varying concentrations of tissue factor and phospholipids, with or without thrombomodulin. Screening tests and specific assays were also performed and activated partial thromboplastin time was shorter in portal plasma samples with higher FVIII and lower protein C levels, well correlated with Child-Pugh scores, and higher D-dimers and F1+2 levels However, all TGA parameters were similar in portal and jugular samples, possibly due in part to similar concentrations of factor II and antithrombin in these two sites of plasma sampling. TGA showed lower thrombin peaks and endogenous thrombin potential values in cirrhotic plasma compared to those of healthy controls. Importantly, a resistance to thrombomodulin that well correlated with factor VIII and PC levels, was evidenced in all samples from patients with cirrhosis, and was more significant in those from severely affected cases. This study therefore supports the existence of a relative hypercoagulability in the portal vein of cirrhotic patients that is likely due to protein C/S deficiency and to high FVIII levels.
 ...
PMID:Comparative study of coagulation and thrombin generation in the portal and jugular plasma of patients with cirrhosis. 2080 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>