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oai:open-archive.highwire.org:alcalc:30/1/1052015-05-19HighWireOUPalcalc:30:1
INCREASED NMDA RECEPTOR AND CALCIUM CHANNEL ACTIVITY UNDERLYING ETHANOL WITHDRAWAL HYPEREXCITABILITY
WHITTINGTON, M. A.
LAMBERT, J. D. C.
LITTLE, H. J.
Original articles
Withdrawal from chronic ethanol administration results in hyperexcitability. In the hippocampus, evoked bursting activity and spontaneous epileptiform events are seen. The present study investigated the effect of ethanol withdrawal on <it>N</it>-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic potentials and on voltage-gated calcium currents, in mouse hippocampal pyramidal cells. The NMDA receptor-mediated component of synaptic excitation was increased during withdrawal, accompanied by an increase in synaptic activation of calcium spikes. Evidence for a direct effect of ethanol withdrawal on calcium channel function was seen in voltage clamp recordings of isolated, slowly inactivating calcium currents. A synergistic effect of increased NMDA receptor and calcium channel function is therefore suggested to contribute to hyperexcitability during ethanol withdrawal.
Oxford University Press
1995-01-01 00:00:00.0
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NEUROPSYCHOLOGICAL DIFFERENCES BETWEEN SONS OF ACTIVE ALCOHOLIC AND NON-ALCOHOLIC FATHERS
OZKARAGOZ, TULIN Z.
NOBLE, ERNEST P.
Original articles
Ten- to fourteen-year-old sons of active alcoholic fathers (<it>n</it> = 59) with a positive family history of alcoholism (AFH+) and sons of social drinker fathers (<it>n</it> = 58) with a negative family history of alcoholism (NFH−) were administered a battery of neuropsychological tasks. Areas of cognitive function which were assessed were memory, visuospatial and attentional abilities and, in addition, motor skills and general intellectual functioning. MANOV As conducted on these measures showed that sons of active alcoholic fathers' performance on the more difficult visuospatial and memory tasks as well as on an attentional test was reduced relative to sons of non-alcoholic fathers.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/115
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EFFECTS OF THE CALCIUM CHANNEL ANTAGONIST DARODIPINE ON ETHANOL WITHDRAWAL IN RATS
COLOMBO, GIANCARLO
AGABIO, ROBERTA
LOBINA, CARLA
REALI, ROBERTA
MELIS, FRANCO
FADDA, FABIO
GESSA, GIAN LUIGI
Original articles
The effect of the dihydropyridine calcium channel antagonist, darodipine, on ethanol withdrawal syndrome was examined in rats made dependent on ethanol by repeated ethanol administration for six consecutive days. Chronic co-administration of darodipine prevented the severity of ethanol withdrawal signs in a dose-dependent fashion. By contrast, acute administration of darodipine during the ethanol withdrawal phase was ineffective in reversing the withdrawal symptoms. The results suggest that the presence of darodipine in the central nervous system during the adaptative responses to ethanol is necessary to reduce the severity of the withdrawal syndrome. They also provide further evidence for a potential clinical usefulness of dihydropyndine calcium channel blockers in treatment of ethanol withdrawal.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/125
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DIAGNOSTIC TESTS FOR ALCOHOL CONSUMPTION
CONIGRAVE, KATHERINE M.
SAUNDERS, JOHN B.
WHITFIELD, JOHN B.
Invited Reviews
A variety of laboratory tests are available to assist in the diagnosis of hazardous alcohol consumption and related disorders. Standard tests, such as serum gamma glutamyltransferase activity and erythrocyte mean cell volume, have limited sensitivity, particularly in detecting non-dependent hazardous consumption. Most also have poor specificity in that results are affected by common diseases and medications. Over the past 10 years a number of new laboratory tests have emerged. One of these, carbohydrate deficient transferrin, has high sensitivity in detecting persons with alcohol dependence, and shows promise for identification of non-dependent hazardous drinking; it is also highly specific. Others such as measurement of bound acetaldehyde, serum β-hexosaminidase and the ratio of urinary serotonin metabolites offer promise in detecting recent heavy drinking. However, many issues remain unresolved. The newer markers have often been judged by contrasting their values in patients who are clearly alcohol dependent and abstainers or very light drinkers. It is now apparent that some are relatively insensitive markers of hazardous consumption. Future research needs to examine the performance of these markers among subjects with a range of alcohol intakes to fully determine their value in assessing drinking history. In addition, assays which are capable of some degree of automation need to be developed for analysing large numbers of samples.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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DIFFERENT AFFINITY OF CORTICAL GHB BINDING SITES IN SARDINIAN ALCOHOL-PREFERRING (sP) AND-NON PREFERRING (sNP) RATS
FRAU, MICHELA
COLOMBO, GIANCARLO
MARCHESE, GIORGIO
STEFANINI, ENNIO
GESSA, GIAN LUIGI
Original articles
Specific gamma-hydroxybutyric acid (GHB) binding sites in cortical membranes of selectively bred alcohol-preferring sP and alcohol-non preferring sNP rats were compared using [2,33H]GHB ligand. The sP rat line showed an increased affinity (-40% lower K<inf>d</inf>) of both the high- and low-affinity sites in comparison with the sNP line. No significant difference in GHB receptor density (<it>B</it><inf>max</inf>) was detected between the two rat lines. The results raise the possibility that differences in GHB binding sites may play a role in the genetic predisposition to ethanol preference in our rat line.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/133
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CALENDAR
Calendar
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/139
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oai:open-archive.highwire.org:alcalc:30/1/140-a2015-05-19HighWireOUPalcalc:30:1
THE BRITISH DOCTORS' AND DENTISTS' GROUP
Notices
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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oai:open-archive.highwire.org:alcalc:30/1/1402015-05-19HighWireOUPalcalc:30:1
MEDICAL COUNCIL ON ALCOHOLISM SUBSCRIPTION RATES 1995
Notices
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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oai:open-archive.highwire.org:alcalc:30/1/272015-05-19HighWireOUPalcalc:30:1
APOLIPOPROTEIN E IN ALCOHOLICS
WEHR, HANNA
BEDNARSKA-MAKARUK, M.
SZACKA, E.
Original articles
In 31 alcohol addicted patients entering detoxication treatment and in 14 social drinkers apolipoprotein E (Apo E) was assayed by radial immunodiffusion in the whole serum and after phosphotungstate Mg2+ precipitation. Serum Apo E level in the intoxicated individuals was increased compared with the controls. The Apo E increase was mostly due to the very low and low density (VLDL + LDL) fraction. The Apo E/cholesterol ratio in this fraction was increased. It is possible that increased Apo E concentration in VLDL contributes to their enhanced uptake by the liver.
Oxford University Press
1995-01-01 00:00:00.0
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SIR NOEL HENRY MOYNIHAN
MADDEN, J S
Obituary
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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HAPPY NEW YEAR, THANK YOU ELSEVIER SCIENCE (PERGAMON PRESS) AND WELCOME TO OXFORD UNIVERSITY PRESS
Badawy, Abdulla A.-B.
Editorial
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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oai:open-archive.highwire.org:alcalc:30/1/312015-05-19HighWireOUPalcalc:30:1
ACTIVITY AND SUBCELLULAR DISTRIBUTION OF PHOSPHATIDATE PHOSPHOHYDROLASE (EC 3.1.3.4) IN ALCOHOLIC LIVER DISEASE
SIMPSON, K. J.
VENKATESAN, S.
MARTIN, A.
BRINDLEY, D. N.
PETERS, T. J.
Original articles
A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/31
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ETHANOL-INDUCED POTENTIATION OF RAT HEPATOCYTE DAMAGE DUE TO 1,2-DIBROMOETHANE
CHIARPOTTO, ELENA
BIASI, FIORELLA
ARAGNO, MANUELA
SCAVAZZA, ANTONELLA
DANNI, OLIVIERO
DIANZANI, MARIO U.
POLI, GIUSEPPE
Original articles
Low amounts of 1,2-dibromoethane (DBE), not able <it>per se</it> to exert pro-oxidant and cytotoxic activity on rat hepatocyte suspensions, become effective when administered with carbon tetrachloride (CCl<inf>4</inf>), due to impairment of the glutathione transferase detoxication pathway by CCl<inf>4</inf>. Treatment of rats with a single dose of ethanol (2.5 g/kg body wt) 2 h before liver cell isolation potentiates the effect of DBE alone on both malonaldehyde formation and lactate dehydrogenase release by the hepatocyte. The potentiation of the DBE effects by ethanol may be through a series of mechanisms, such as a strong inactivation of hepatocyte glutathione transferase similar to that caused by CCl<inf>4</inf>, an increased basal level of lipid peroxidation and a significant loss of total glutathione.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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oai:open-archive.highwire.org:alcalc:30/1/472015-05-19HighWireOUPalcalc:30:1
THE INFLUENCE OF CHRONIC ETHANOL ADMINISTRATION ON ADRIAMYCIN-INDUCED NEPHROTIC SYNDROME IN RATS
TESAR, V.
ZIMA, T.
POLEDNE, R.
STEJSKALOVÁ, A.
STÍPEK, S.
TEMÍNOVÁ, J.
Original articles
Alcoholic liver disease may be frequently complicated by mesangial proliferation with the deposition of IgA in glomeruli and glomeruloscierosis, but these glomerular lesions are usually mild and without greater impact on renal function. To evaluate the putative role of ethanol in glomerular pathology we studied the influence of chronic ethanol administration on the development of experimental adriamycin nephropathy in rats. Nephrotic syndrome was induced by a single i.v. dose of adriamycin (5 mg/kg body wt) both in rats given ethanol at a dose of 4 g/day for 3 months and control rats given standard chow. Further controls on both diets without adriamycin administration were also studied. Blood and urine were examined before and 3 and 6 weeks after adriamycin administration. All rats were killed and examined histologically 6 weeks after adriamycin administration. Ethanol fed nephrotic rats were more catabolic than control nephrotic rats (with higher free fatty acids, lower glycaemia, higher urea with similar creatinine) and had lower proteinuria (0.55 ± 0.34 versus 5.79 ± 3.15 g of protein/mmol of creatinine, <it>P</it><0.05), higher albuminaemia (5.41 ± 2.62 versus 1.92 ± 1.94 g/l, <it>P</it><0.01), lower plasma cholesterol (6.54 ± 2.6 versus 10.57 ± 2.92 mmol/l. <it>P</it><0.01) and triglycerides. The development of nephrotic syndrome and renal morphological changes after adriamycin administration in rats seemed to be ameliorated, or at least delayed by chronic ethanol feeding with much milder and focal glomerulosclerosis as compared with more severe and diffuse glomerulosclerosis in control nephrotic animals. The mechanism of this effect of chronic ethanol feeding remains to be elucidated. Metabolic, immunosuppressive and pharmacological effects of ethanol should be taken into consideration.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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ALCOHOL INTOXICATION IN CHILDHOOD AND ADOLESCENCE
LAMMINPÄÄ, ANNE
Invited Reviews
Coma and vomiting are the commonest symptoms in young teenagers intoxicated by alcohol. Severe toxicity, manifested as coma, occurs at lower blood alcohol concentrations in young teenagers than in adults. The effect of ethanol on the state of consciousness is directly proportional to blood alcohol concentration. Among children under 5 years of age the risk of hypoglycaemia is increased. A significant risk in acute alcohol intoxication is the rapid development of coma, which in cold environments could lead to fatal hypothermia. Preschool-age children are reported to eliminate ethanol twice as fast as adults, whereas young teenagers eliminate it at the adult rate. The biochemical disturbances in children 11 to 16 years of age with alcohol intoxication resemble those of adults. Mild acidosis of a respiratory or metabolic origin and mild hypokalaemia are common findings in young teenagers. Fluid replacement with glucose-containing fluids and follow-up are generally the only treatments needed for complete recovery. Motives leading to alcohol intoxication are a wish to get drunk, experimenting, problems in human relations, and attempted suicide. The underlying problems are often family-related. such as divorce, an alcoholic parent and a lower socioeconomic group.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/5
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CLINICAL IMPACT OF DRUG ADDICTION IN ALCOHOLICS
JIANG, J.-J.
DUBOIS, F.
DRISS, F.
CARNOT, F.
THEPOT, V.
POL, S.
BERTHELOT, P.
BRECHOT, C.
NALPAS, B.
Original articles
Careful interviewing of alcoholics who wish to undergo alcohol withdrawal programmes reveals that some are past intravenous drug abusers. As these two potentially hepatotoxic types of substance abuse could cause liver disease or influence its clinical course, we studied biological, histological and virological features in 26 alcoholics with a past history of intravenous (i.v.) drug abuse, compared with paired controls (alcoholics without i.v. drug abuse). There were no differences with regard to routine liver test results. In contrast, the former drug abusers had a significantly higher prevalence of serum markers of hepatitis C (76.9%) and hepatitis B viruses (76.9%) than the other patients (16.7 and 12.5%, respectively). Eight patients, all of whom were HBs Ag negative, were positive for serum HBV-DNA; three were former drug abusers and five were not, giving an overall prevalence of HBV markers in the two groups of 80.8 and 25%, respectively. Two former drug abusers had anti-HIV antibodies and one had anti-hepatitis delta virus antibodies. Ten of the 17 former drug abusers who underwent liver biopsy had histological signs of viral infection. These data underline the need for careful interviews of alcoholic patients, together with serological tests for viral infections and histological analysis of the liver, as some will have liver-damaging viral diseases and may be candidates for anti-viral (i.e. interferon) treatment.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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CARBOHYDRATE DEFICIENT TRANSFERRIN LEVELS IN HAZARDOUS ALCOHOL CONSUMPTION
GODSELL, PAUL A.
WHITFIELD, JOHN B.
CONIGRAVE, KATHERINE M.
HANRATTY, STEVEN J.
SAUNDERS, JOHN B.
Original articles
Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (>100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; <it>P</it> <0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/61
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SEVERITY OF ALCOHOL DEPENDENCE IN THE EAST END OF GLASGOW
JAUHAR, P.
WATSON, A. S.
Original articles
A survey of 100 consecutive admissions for alcohol abuse in 1990 highlights the severity of alcohol dependence in the East End of Glasgow. The survey identifies a specific sub-group of heavy drinkers who consume strong lager, usually in open spaces, referred to locally as ‘garden parties’. In the total population, males outnumbered females 3:1 with a mean consumption of 268 and 230 units of alcohol per week, respectively. The severity of alcohol abuse was reflected in their social, physical and central nervous system complications. Two-thirds of the population had a family history of alcohol abuse. Over three-quarters of the population showed self neglect with nearly half the males ascribing their marital breakdown or family neglect directly to their drinking problem. Both sexes showed a high prevalence of history of paraesthesiae, while half the male population had clear signs of peripheral neuropathy on admission. A history of delirium tremens in over 50% of the population with a history of seizures in 21% of males and 35% of females indicates central nervous system involvement. Three sub-groups were identified: history of delirium tremens, history of persecutory ideation and history of serious criminality. All three sub-groups had a shorter length of drinking with higher consumption and increased frequency of ‘garden parties’ than the group as a whole. This survey reinforces the need for appropriate in-patient detoxification and rehabilitation facilities for patients with severe alcohol dependence, to reduce their impact on other health, social work and criminal justice services.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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DANGEROUS JOBS AND HEAVY ALCOHOL USE IN TWO NATIONAL PROBABILITY SAMPLES
LEIGH, J. PAUL
Original articles
Samples of employed persons within the US were drawn from the National Health and Nutrition Examination Survey II (<it>n</it> = 8477), and the Quality of Employment Survey (<it>n</it> = 1393) to test the hypothesis that a positive association existed between alcohol use and job hazards. Heavy total alcohol use, or beer or wine or liquor use separately, were the dependent variables. The key independent variables included subjects' evaluations of hazardous nature of the job and fatality rates within occupations and industries. Models were estimated with logistic regressions controlling for age, gender, race and other covariates. Only one robust finding emerged: heavy beer use was found to be positively and strongly correlated with the fatality rate within occupations. Additional correlations between job hazards and heavy alcohol use were weak, generated large <it>P</it> values, and some suggested an <it>inverse</it> association. The lack of robust findings for the additional correlations may partially be explained by the associations between job categories on the one hand and choice of beverage on the other. Blue-collar jobs are more hazardous than white-collar jobs, on average. Persons in blue-collar jobs were more likely to drink beer, while those in white-collar jobs were more likely to drink wine or liquor (spirits). Separate analyses of beer, wine and liquor appeared essential to explaining correlations between dangerous jobs and heavy alcohol use in these data. Limitations of the study included (1) age of the data (from the 1970s), (2) alcohol use and some job hazards were measured by self-report, and (3) data were from only one country
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/71
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oai:open-archive.highwire.org:alcalc:30/1/872015-05-19HighWireOUPalcalc:30:1
MEASUREMENTS OF DENDRITIC PATH LENGTHS PROVIDE EVIDENCE THAT ETHANOL-INDUCED LENGTHENING OF TERMINAL DENDRITIC SEGMENTS MAY RESULT FROM DENDRITIC REGRESSION
PENTNEY, ROBERTA J.
Original articles
The present study proposed to determine the significance of previously reported ethanol-induced dendritic lengthening in mature cerebellar Purkinje neurons (PN). An analysis of dendritic path lengths (PL) was used to make this determination. A PL is the curvilinear length from the origin of the dendritic root segment to the free tip of a dendritic terminal. It was hypothesized that treatment-induced dendritic lengthening resulted from dendritic growth, and that growth should produce an upward shift in the value of the median PL. The PL and the segment length (SL) for each dendritic terminal were measured in PN of 24 month old male F344 rats, previously fed a liquid diet containing 35% ethanol-derived calories for 48 weeks, to test that hypothesis. Because there are large numbers of terminal dendrites in PN networks a shift in the value of their median PL is a sensitive measure of change in these networks. It was found that almost 30% of the ethanol-exposed cell sample had median PL that were shorter than expected and that the median SL in these same neurons tended to be longer than expected. At the end of the ethanol treatment, half of these rats were weaned from the ethanol diet for a subsequent 8 weeks to test for reversibility of these changes. Following the period of abstinence from dietary ethanol, the significant ethanol-related differences previously found in dendritic lengths were no longer present. A consideration of two models of dendritic regression suggested that elongation of surviving terminal dendritic segments in the ethanol-exposed neurons occurred through deletion of other terminal segments at their vertices (branch points). It was shown that deletions of entire terminal dendritic segments at their vertices would produce increases in the lengths of associated terminal segments in the absence of real growth. Deletions of dendritic segments would also entail loss of PL unique to the deleted segments, thereby causing a shift in the value of the median PL of affected networks.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/30/1/87
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DETECTION OF HEPATITIS C VIRUS ANTIBODIES AND HEPATITIS C VIRUS RNA IN PATIENTS WITH ALCOHOLIC LIVER DISEASE
BODE, JOHANN CHRISTIAN
ALSCHER, DOMINIK MARK
WISSER, HERMANN
BODE, CHRISTIANE
Original articles
The prevalence of hepatitis C virus (HCV) antibody was determined in 130 patients with alcoholic liver disease using a second-generation anti-HCV enzyme immunoassay (ELISA 2) and confirmed by a sensitive polymerase chain reaction procedure measuring HCV RNA. Hepatic disease was evaluated by clinical and biochemical studies and, whenever possible, by liver biopsy. Seventy-one patients were diagnosed as having cirrhosis, and 59 alcoholic hepatitis (<it>n</it> = 33) or fatty liver (<it>n</it> = 26). The prevalence of anti-HCV in the total group was 9.2% and did not differ significantly in the cirrhotics (11.3%) as compared with the non-cirrhotics (6.8%). HCV RNA was detected in six out of eight cirrhotics and three Out of four non-cirrhotics who were ELISA 2 positive. A positive test for antibodies to hepatitis core antigen (anti-HBc) was more frequent in anti-HCV-positive patients (75%) than in the anti-HCV-negative group (14%, <it>P</it><0.001). Anti-HBc was also found more frequently in the cirrhotics (25.4%) than in the alcoholics without cirrhosis (11.9%). However, the prevalence of hepatitis B surface antigen was equally low in both groups (cirrhotics 1.4%, non-cirrhotics 1.7%). No correlation was observed between the prevalence of anti-HCV antibodies and the severity of liver dysfunction. These results indicate that HCV, and especially HCV-viraemia, is less frequent in alcoholics in southern Germany than suspected in previous studies, and that the prevalence of HCV markers in alcoholics has been overestimated by ELISA 1 used alone.
Oxford University Press
1995-01-01 00:00:00.0
TEXT
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