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)

Four hundred and four patients (273 men, 131 women) aged 3 to 85 years with chronic Hepatitis B virus (HBV) infection seen during a five year period were analysed. At presentation, 177 patients (44%) were Hepatitis B e Antigen (HBeAg) positive (mean age 32 years) and 217 patients (54%) were anti-HBe-positive (mean age 40 years). Ten patients (2%) were negative for HBeAg and anti-HBe. Serum HBV-DNA was detected in 169 patients (42%). 85% of the HBeAg-positive patients had detectable serum HBV-DNA and 9% of the HBeAg-negative patients were positive for serum HBV-DNA. The mean serum Alanine amino-transferase (ALT) and Aspartate amino-transferase (AST) levels were higher in HBeAg-positive patients (75 and 52 iu/l) than in HBeAg negative patients (46 and 37 iu/l) (P less than 0.001). Liver biopsies were performed in 135 patients. Fifty-three (39%) had minimal changes, 61 (45%) chronic hepatitis (CPH, CLH & CAH) and 21 (16%) cirrhosis. There was no significant difference in the histologic distribution between HBeAg-positive and HBeAg-negative groups. Two hundred and fifty eight patients were followed up for a mean duration of 2 years (range 3 to 108 months). The cumulative probability of clearing HBeAg at the end of the first, second and third year were 14%, 16% and 18% respectively. Of these, the cumulative probability of developing anti-HBe over one, two and three years were 8%, 9% and 11% respectively. Reversion to HBeAg occurred in 1.5% of patients who were HBeAg-negative at presentation and 11% of HBeAg-positive patients who cleared HBeAg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic hepatitis B infection in Singapore. 179 64

The amino acid composition of proteins from liver mitochondrial membranes has been studied in patients with normal liver, with biliary diseases and fatty liver, with obstructive jaundice or liver cirrhosis. A characteristic pattern of the amino acid composition in patients with normal liver has been found. In the mitochondrial membranes of patients with fatty liver tryptophan and lysine were decreased while [aspartic acid plus asparagine] and [glutamic acid plus glutamine] were increased compared to their counterpart in the normal liver. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in methionine content was found, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of human liver mitochondrial membranes in normal and pathological conditions. 186 76

Amino acid levels were measured in the plasma and ascitic fluid of 13 alcoholic patients with liver cirrhosis and of 14 normal controls. The plasma aromatic amino acids of the alcoholic patients were not statistically different from those of the control subjects, whereas the levels of branched-chain amino acids were reduced (P less than 0.05). The values for the ratio of the muscle/liver metabolized amino acids (valine + isoleucine + leucine)/(phenylalanine + tyrosine + methionine) were statistically lower in the cirrhotic patients both in plasma and ascitic fluid (P less than 0.05). The amino acid levels in the ascitic fluid of the cirrhotic patients were slightly lower than those in the plasma of the same patients and the values for the muscle/liver metabolized amino acid ratio were similar in plasma and ascitic fluid. Aspartic acid, glutamic acid and glycine levels were higher among the cirrhotic patients (P less than 0.05). Cirrhotic patients present an alteration in amino acid metabolism which creates a different amino acid pattern in both plasma and ascitic fluid. The significance of the proposed ratio and its possible relation to hepatic failure are discussed.
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PMID:Amino acid patterns in the plasma and ascitic fluid of cirrhotic patients. 383 4

The amino acid composition of proteins from liver microsomes has been studied in rats and in human subjects with normal liver, with obstructive jaundice or liver cirrhosis. The pattern of the amino acid composition of microsomes appeared to be species-specific. Phenylalanine, threonine, serine, proline, histidine and [aspartic acid plus asparagine] were increased, while alanine, tyrosine, glycine and arginine were decreased in the human compared to the rat microsomes. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in leucine and phenylalanine could be noticed, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of rat and human liver microsomes in normal and pathological conditions. 757 35

A novel copper-binding protein was identified in the liver supernatant (100,000 x g) of Indian childhood cirrhosis (ICC), purified to apparent homogeneity and characterized [corrected]. Purified major copper-binding protein (MCuBP) is solely responsible for binding about 35% of the total supernatant copper. Elution profile of ICC liver supernatant on Sephadex G-75 column chromatography showed three peaks. About 60% of the total supernatant copper was resolved in peak II, whereas zinc content was insignificant in this peak. But peak II was almost missing in a gel elution profile of control liver supernatant. The control group included cases of various liver diseases viz. neonatal hepatitis, septicemia, and mixed nodular cirrhosis. Copper-binding proteins of peak II further purified on ion-exchange chromatography and elution profile showed that peak II was a MCuBP with high copper-binding capacity (10 g atoms/mol of native protein). SDS-PAGE of this protein also revealed the existence of a single band with molecular mass of about 50 kD. UV spectra of MCuBP showed the maximal absorbance at 254 nm. Unlike the classical metallothionein, the amino acid composition of MCuBP revealed the presence of aromatic amino acids and higher content of glutamic acid and aspartic acid followed by glycine and serine. The ratio (0.3) of basic amino acids to acidic amino acids strongly indicates that it is an acidic protein. The cysteine content in this protein was insignificant, which further corroborates the possibility that the acidic amino acids might be prominent candidates for binding copper. Thus, the 50-kD MCuBP apparently makes a major contribution to the total copper-binding activity in ICC liver cytosol and may play a significant role in hepatic intracellular copper accumulation.
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PMID:Identification of a novel copper-binding protein from the liver of Indian childhood cirrhosis: purification and physicochemical characterization [corrected]. 980 48

Treatment of chronic hepatitis B is directed at interrupting the natural history and clinical outcomes of the disease. It needs to take into account the virology and replication cycle of the hepatitis B virus (HBV), and the host immune response to HBV. Long term follow-up of patients treated with interferon supports the paradigm that a sustained, major suppression of HBV replication, particularly that associated with hepatitis B e antigen (HBeAg) seroconversion, interrupts the natural history of hepatitis B. The availability of potent but well tolerated and orally available HBV antivirals, of which lamivudine is the prototype, has allowed clearer treatment objectives to be formulated. These are: temporary or permanent reduction of hepatitis (necroinflammatory) activity, arrest of fibrotic progression, prevention of cirrhosis and liver failure, and prevention of recurrent HBV infection after liver transplantation. Lamivudine has good medium term efficacy in achieving each of these objectives. The only significant problem for the longer term is emergence of antiviral resistance conferred by mutations in the YMDD (tyrosine-methionine-aspartic acid-aspartic acid) motif of the HBV reverse transcriptase. As a result, contentious issues remain about defining when antiviral therapy is indicated, whether to treat for a defined interval or indefinitely, and when to stop treatment if HBeAg seroconversion is not achieved. Some personal views are expressed in this review. Among newer HBV antivirals in clinical studies, adefovir dipivoxil, entecavir and emtricitabine appear to be at least as potent as lamivudine in suppressing HBV replication. Famciclovir appears less potent. In vitro studies show that YMDD mutations confer cross-resistance between lamivudine, emtricitabine and beta-L-Fd4C (L-2',3'-didehydro-dideoxy-5-fluorocytidine). However, adefovir dipivoxil, lobucavir, entecavir, DAPD (beta-D-2,6-diaminopurine dioxolane) and possibly clevudine (L-FMAU) suppress replication of YMDD mutant HBV, as well as wildtype. Preliminary studies indicate clinical efficacy of adefovir dipivoxil once resistance to lamivudine has developed. Immunomodulatory approaches to treatment of chronic hepatitis B are conceptually attractive, but newer agents used to date (thymalfasin, interleukin-12, therapeutic vaccines) have not demonstrated sufficient efficacy for widespread use. The next challenge for HBV treatment is to use antivirals in combination and/or in cyclical therapy to reduce the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post-treatment suppression of hepatitis B.
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PMID:Clinical potential of emerging new agents in hepatitis B. 1108 96

The paleopathological study of 40 Italian Renaissance mummies has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 4 metabolic (obesity, atherosclerosis, gallstones and uric acid nephrolithiasis), 2 articular (DISH and rheumatoid arthritis) and 2 neoplastic (skin apithelioma and colon adenocarcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (C14=1569 +/- 60), presented a diffuse vesiculo-pustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM reavealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria of Aragon, Marquise of Vasto (1503-1568), reavealed on the left arm an oval, cutaneous ulcer (15x10 nm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. EM evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. The mummy of Ferrante I of Aragon, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12:the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a fatal puerperal complication, a thyroid goiter, a case of Wilson's cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of the wealthy classes of the Italian Renaissance.
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PMID:Renaissance mummies in Italy. 1162 3

We describe a 47-year-old patient who developed cholelithiasis in adolescence, followed by recurrent intrahepatic cholestasis of pregnancy, and finally biliary cirrhosis in adulthood. In our patient, the consecutive presentation of the 3 mentioned disorders raised the suspicion of a defect of MDR3, the canalicular protein involved in the transport of phospatidylcholine to bile. Mutational analysis in our patient showed a heterozygous missense mutation of the MDR3 gene that has not been described previously, which occurs in exon 14 at codon 535, and results in the substitution of glycine for aspartic acid. Further analysis of 7 members of the family showed the same mutation in her daughter who, on follow-up, developed cholestasis of pregnancy and persisting high serum levels of gamma-glutamyl transpeptidase and alkaline phosphatase after delivery. Although biliary cirrhosis associated with MDR3 deficiency typically appears before the age of 25 years, in our case, the relatively mild MDR3 dysfunction allowed for a slower progression of the disease with established, well-advanced cirrhosis in the fifth decade of life. The present case, which accumulates the 3 clinical disorders assocaited with MDR3 deficiency, shows that this condition should be suspected not only in children or young people with high gamma-glutamyl transpeptidase cholestasis but also in middle-aged or older patients with chronic idiopathic cholestasis, especially when there is a previous history of cholestasis of pregnancy or juvenile cholelithiasis.
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PMID:A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis. 1472 40

Chronic alcohol consumption is associated with increased incidence of variety of illnesses including cirrhosis. Studies have shown that ethanol consumption may result in increased oxidative stress with increased formation of lipid peroxides and free radicals. However, very few reports are available on their involvement in the toxicity of alcoholic cirrhosis. The present study was undertaken in 44 male subjects to evaluate the role of oxidative stress in liver injury with special reference to alcoholic or non alcoholic cirrhosis. It was observed that the parameters of liver function like total bilirubin, Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), gamma Glutamyl transfarase (gammaGT) were increased in cirrhotic (alcoholic or non alcoholic) patients as compared to normal controls. However antioxidant enzymes like Superoxide dismutase (SOD) and Glutathine peroxidase (GPx) lipid peroxidation marker, Malondialdehyde (MDA) showed significant changes only in alcoholic cirrhosis and not in non alcoholic cirrhosis when compared with normal controls. The possibility of assessment of antioxidant enzymes to differentiate between alcoholic or non alcoholic or non alcoholic cirrhosis is postulated.
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PMID:Status of blood antioxidant enzymes in alcoholic cirrhosis. 1472 22

Knowledge of the physiopathological basis of the fibrogenesis in the hepatopathy by hepatitis C virus (HCV) is critical. We describe the evolution of the infection by HCV after a ten-year follow-up in patients with antibody immunodeficiency (common variable immunodeficiency (n=3) (IDVC), IgG subclasses deficiency (n=2), specific deficiency of antibodies formation (n=1). The patients were treated with a prepared intravenous immunoglobulin that was associated later with an HCV hepatitis outbreak. Five of the six patients had a positive overwhelming course (CRP) for HCV and all have changes in their hepatic biochemistry during the exposure period [ Analine Aminotransferase (ALT) (from 280 to 2720 U/L) and Aspartate Aminotransferase (AST) (from 400 to 2600) U/L)]. In less than one year, two patients with IDVC developed cirrhosis and the other patient with IDVC, an active chronic hepatitis while the other patients cured the infection without the treatment. The patients with IDVC presented lower IgG levels than the patients with antibodies deficiency before the exposure (average: seric IgG = 697 mg/dl and 1480 mg/dl respectively) and had, in addition, lower T CD4+ lymphocytes [average: T CD4+ lymphocytes = 22% (413 x 106 cells/l) and 33% (869 x 106 cells/l) respectively)]. One combination of components of humoral and cellular immunodeficiency could play a role in the accelerated evolutive course of the hepatopathy by HCV in patients with IDVC.
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PMID:[Overwhelming course of HCV disease in patients with hypogammaglobulinemia associated with cellular immunity deficiency]. 1581 19


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