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

A case of type III hyperlipoproteinemia (HLP) (dysbetalipoproteinemia) acquired by liver transplantation is reported. The 50-year-old female patient was referred to the Frankfurt University Hospital for orthotopic liver transplantation. She had suffered from ethylic liver cirrhosis. The donor liver showed discrete signs of steatosis. The postoperative course of the patient was satisfactory. Enzyme levels and blood coagulation tests returned to normal within thirty days. However, both cholesterol and triglycerides gradually increased from approximately 2.00 g/L to values ranging from 2.50 to 3.50 g/L within 200 days after transplantation. Cutaneous xanthomas did not develop. The patient's lipoprotein pattern met the criteria of type III HLP: the cholesterol to triglyceride ratio in very low-density lipoproteins (VLDL) was 0.64. Intermediate-density lipoprotein(IDL) cholesterol was 0.48 g/L. Lipoprotein electrophoresis showed a broad beta-band, and beta-migrating particles were present in VLDL. Immunoblotting of apolipoprotein (apo) E from the patient's plasma revealed an E2/2 phenotype. However, restriction isotyping of an in vitro amplified apoE gene fragment showed the genotype of the patient to be epsilon 3/epsilon 4. These data suggest that the development of type III HLP in this patient was due to a change in the apoE phenotype from E3/4 to E2/2 after liver transplantation.
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PMID:Type III hyperlipoproteinemia acquired by liver transplantation. 843 77

Over the last few years, lipoprotein(a) [Lp(a)] levels have been investigated because clinical studies have related it to increased cardiovascular and cerebrovascular risk. Although it is known that serum Lp(a) concentrations are controlled genetically, little is known about its metabolism. We studied changes in the lipid profile and Lp(a) values in 57 patients (34 males and 23 females) affected by cirrhosis of the liver subdivided into Child's classes in order to assess whether this lipoprotein is sensitive to reduced liver protein synthesis. The patients presented with low total cholesterol, normal HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), triglycerides, apoprotein A1 (Apo-A1) and apoprotein B100 (Apo-B100) concentrations, while Lp(a) concentrations seemed elevated. Grouping the patients into Child's classes revealed that all the lipid parameters investigated reduced as the disease progressed. Lp(a) reduced significantly between Child's Classes I and II and seems to be correlated with the severity of cirrhosis and the clinical worsening of the patients' conditions. These findings suggest that Lp(a) is not only an index of atherosclerosis risk, but also plays a role in monitoring liver functions.
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PMID:Lipoprotein(a) in cirrhosis. A new index of liver functions? 901 Jun 14

Serum gamma-glutamyltransferase (GMT) is prevalently of hepatic origin, and its activity has long been known to be increased in most patients with hepatobiliary diseases. The different isoforms of GMT in serum, particularly those found in the course of hepatobiliary diseases, are associated with various lipoproteins. An important fraction of GMT activity is associated with apoprotein B in patients with icteric or anicteric cholestasis. We have studied the association of GMT activity with LDL and VLDL lipoproteins in patients with chronic liver diseases and the possibility to use this laboratory test in discriminating liver malignancies from other liver diseases. Thirty-eight healthy subjects, aged between 19 and 45 years, and 38 patients with liver cirrhosis, 7 with liver tumor, 16 with chronic active hepatitis and 5 with primary biliary cirrhosis were studied. Serum GMT activity complexed with LDL+VLDL was estimated according to Sacchetti et al. A cut-off of 40 U.l-1 of GMT complexed with VLDL+LDL results in a diagnostic sensitivity of 85% for liver tumor patients, and a diagnostic specificity of 87% and 65% towards the chronic active hepatitis or liver cirrhosis, respectively. According to our results, this test could be a useful contribution to laboratory tests that serve to discriminate chronic hepatopathies from liver malignancies. Our results are in agreement with the results published by Sacchetti et al. 1988, 167-172). (Tab. 1, Fig. 1, Ref. 15.)
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PMID:[Use of gamma glutamyltransferase isoenzymes in the differentiation of chronic liver diseases]. 926 17

Shosaikoto, a Kampo medicine used clinically to treat patients with chronic hepatitis or cirrhosis in Japan, displays immunoregulatory effects, especially on macrophage functions. Oral administration of shosaikoto influences the synthesis of humoral factors such as the interleukins, nitric oxide and prostaglandins in macrophages. In addition, phagocytic activity is enhanced by treatment with shosaikoto, resulting in an antigen that is effectively presented to T lymphocytes to produce more antibodies. The role of macrophages in the pathogenesis of atherosclerosis is well recognized, although a therapeutic agent targeted at macrophages has not yet been developed. When shosaikoto was administered to atherosclerotic rabbits, it did not exhibit antihyperlipidemic effects but did reduce the formation of atherosclerotic lesions. In addition, treatment with shosaikoto suppressed intimal hyperplasia in apoE-deficient mice fed a cholesterol-enriched diet for nine weeks. Biochemical studies demonstrated that the mechanism of the antiatherosclerotic effect was partly due to the increase of oxidized low-density lipoprotein (oxLDL) elimination by macrophages, resulting from stimulation of oxLDL uptake through scavenger receptors, activation of acyl-CoA:cholesterol acyltransferase and neutral cholesteryl ester hydrolase, and increase of cholesterol elimination by high-density lipoprotein. Furthermore, shosaikoto is able to reverse the depression of macrophage functions caused by hyperlipidemia. These results indicate the potential of this medicine as a new type of preventive or therapeutic agent for atherosclerosis.
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PMID:Shosaikoto as a potential antiatherosclerotic agent. 1293 13

Hepatitis C virus (HCV) is a major etiologic agent for chronic hepatitis worldwide often leading to the development of cirrhosis and hepatocellular carcinoma. However, the mechanism for development of chronic hepatitis or hepatocarcinogenesis by HCV remains unclear. HCV NS5A protein possesses many intriguing properties, including sequestration of p53 in the cytoplasm, downregulation of p21 protein, activation of STAT3, and inhibition of tumor necrosis factor-alpha-mediated apoptosis. Thus, we investigated whether this viral protein has oncogenic property in vivo. In the absence of an efficient cell culture system for virus growth and a suitable small animal model for HCV infection, transgenic FVB mice were generated by targeting the HCV NS5A genomic region cloned under the control of a liver-specific apoE promoter or mouse major urinary promoter (MUP). The apoE promoter is constitutively expressed in liver, on the other hand, the MUP is developmentally regulated and expressed in the liver after birth. Reverse transcription polymerase chain reaction and Western blot analysis indicated establishment of HCV NS5A transgene expression in several lines from both groups of mice. Immunohistochemical studies suggested the presence of NS5A in the cytoplasm of hepatocytes. The transgenic animals were phenotypically similar to their normal littermates and did not exhibit a major histological change within the liver up to 24 months of age. Our results suggested HCV NS5A protein is not directly cytopathic or oncogenic in this FVB transgenic mouse model, although this viral protein promotes cell growth in vitro. These animals will be a valuable model of HCV immunopathology as well as for evaluation of siRNA, interferon and other cytokine therapies.
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PMID:Expression of hepatitis C virus non-structural 5A protein in the liver of transgenic mice. 1467 68

High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.
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PMID:Liver disease alters high-density lipoprotein composition, metabolism and function. 2710 40


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