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B Nalpas

Publications and source records attributed to B Nalpas.

At least 73 records · Page 4Linked to original sources

Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease.

We conducted a retrospective study in 229 patients to determine the prevalence of hepatitis C virus (HCV) according to the type of liver disease and also the serum hepatitis B virus (HBV) status. There were 55 cases of hepatocellular carcinoma (HCC), 78 cases of alcoholic cirrhosis (AC) and 96 cases of non-cirrhotic alcohol liver disease (NCA). Half the AC and NCA groups were constituted of patients with or without serum HBV markers. The prevalence of anti-HCV antibodies in HCC (58.2%) was significantly higher than in the other groups (AC, 35.9%; NCA, 17.7%). Combining the two AC and NCA groups gave a 25.8% anti-HCV prevalence in the alcoholics. Altogether anti-HCV antibodies were more frequently present in HBV-positive than in HBV-negative patients (42.2 vs. 26.1%, p less than 0.01), although the difference was not significant when the HCC group was separately analysed. The S/N ratio of anti-HCV-positive samples varied according to the type of the disease (tumorous vs. non-tumorous) and to the serum HBV status. Indeed, 65.6% of HCC had a S/N greater than 4 compared to only 32.2 and 23.5% in AC and NCA, respectively (p less than 0.01). On the other hand more than half of the AC and NCA had a S/N less than 2, indicating possible artefacts in certain cases. The 15 HBsAg and anti-HCV-positive patients had a significantly lower mean S/N than patients displaying only antibodies against HBV, even in the HCC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Hepatic activity and mRNA expression of aspartate aminotransferase isoenzymes in alcoholic and nonalcoholic liver disease.

In liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well-known increase of serum mitochondrial AST-to-total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples. Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close-to-normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms.

Aspartate Aminotransferases↗

[Significance of isolated anti-HBs antibodies in subjects not vaccinated against hepatitis B viruses].

The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective.

Adult↗

Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen.

BACKGROUND AND METHODS: The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan). RESULTS: Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested. CONCLUSIONS: Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.

Adult↗

Liver collagen mRNA and serum amino-terminal peptide of type III procollagen (PIIINP) levels in patients with alcoholic liver disease.

We have investigated the alpha 1 (I), alpha 2 (I) and alpha 1 (III) liver collagen mRNA levels in 38 patients with alcoholic liver disease. The patients were divided into 3 groups according to the severity of their liver disease. Liver collagen mRNA levels were estimated by densitometric analysis after hybridization with the corresponding cDNA. Serum amino-terminal peptide of type III procollagen (PIIINP) was determined by radioimmunoassay in 30 patients. The results indicated that there was no increase but rather a decrease in the liver alpha 1 (I), alpha 2 (I) and alpha 1 (III) collagen mRNA in patients with the most severe liver lesions as compared to those with minimal changes. This decrease was significant for alpha 2 (I) and alpha 1 (III) cDNA probes. In contrast, serum PIIINP levels showed a positive correlation with the severity of the disease. Thus this study indicates that collagen accumulation in the liver as well as elevation of the serum PIIINP during the development of alcoholic liver disease probably reflects posttranscriptional events in collagen synthesis.

Collagen↗

Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake.

Cytochromes P450 (P450) are a family of isozymes which play an important role in xenobiotic metabolism. The concentration of three P450 isozymes, namely P450-IIE1(A1c),-IIIA(NF) and -IIC8-10(MP) has been measured in human liver biopsies of patients with different alcohol and drug intake status. All these three P450s were expressed in all subjects. Ethanol intake increased P450-IIE1(A1c) content with no effect on the content of the two other P450s. Drug intake (barbiturates) increased both P450-IIIA(NF) and -IIC8-10(MP) content without any effect on P450-IIE1(A1c). This paper brought, at protein level, further evidence of the importance of environmental conditions on P450 isozyme pattern, and therefore, on drug metabolizing capacity of human liver.

Adult↗

Assessment of the transferrin index in screening heavy drinkers from a general practice.

The aim of this study was to assess the performance of the transferrin (Tf) index in screening heavy drinkers and to compare its performance to that of gamma glutamyl transpeptidase (GGT). Tf index, GGT, and transaminase activities were determined in a group of 173 subjects (49% males) recruited in a family doctor's practice (age: 54 +/- 1.5 yr; daily alcohol intake: 32 +/- 3.5 g; mean +/- SEM). Tf subfractions were quantified by isoelectric focusing and immunofixation on polyacrylamide gel. The Tf pl 5.7 to 5.4 ratio, or Tf index, was used as a marker of excessive drinking, with a cut-off point at 7%. Alcohol consumption was assessed through a face-to-face interview. Excessive drinkers were defined as those with a daily alcohol intake greater than 80 g over at least 2 years; 20 were classified as excessive drinkers (alcohol consumption: 92-232 g/day). All but four had normal transaminase activities indicating the low prevalence of hepatic impairments in this sample. The Tf index was found to have a sensitivity of 45%, specificity 89%, positive predictive value 35%, negative predictive value 92%. The corresponding results for GGT were 52%, 80%, 27%, and 92%, respectively. Concordance between the Tf index and GGT was assessed by the kappa coefficient (kappa) which was 0.22 indicating poor agreement between the two markers in selecting excessive drinkers (perfect association: kappa = 1, no association: kappa = 0).

Alcoholism↗

Evaluation of mAST/tAST ratio as a marker of alcohol misuse in a non-selected population.

Serum mitochondrial aspartate aminotransferase (mAST) and gamma-glutamyl transpeptidase activities were measured in 303 outpatients upon visits to their general practitioner. Alcohol consumption was evaluated by interview, using a standard questionnaire. Thirty-four patients drank more than 80 g of alcohol per day but none complained of an alcohol-related disease. These 34 heavy drinkers presented a mean serum mAST value which was significantly higher than that of the 269 normal drinkers; however, only 14 out of the 34 (41%) exhibited an increased mAST value. The sensitivity, specificity and predictive positive value of the mAST/tAST ratio were 0.29, 0.77 and 0.13, respectively; the corresponding figures for GGT were 0.5, 0.81 and 0.23, respectively. These results are in sharp contrast with those obtained for mAST activity in a population of hospitalized alcoholics. The explanation may lie in differences in alcohol consumption, in nutritional status and in the frequency of alcohol-related diseases in inpatients as compared to outpatients.

Adult↗

Nucleotide sequence and tissue distribution of the human mitochondrial aspartate aminotransferase mRNA.

The cDNA of human mitochondrial aspartate aminotransferase (E.C.2.6.1.1.) was isolated from a human liver cDNA library using a rat mitochondrial aspartate aminotransferase cDNA as probe. The sequence of this cDNA gives a predicted aminoacid sequence for the human presequence and for the human mature protein exhibiting respectively 93% and 95% homology with rat sequences. A Northern blot of total RNA, isolated from various human tissues and hybridized with this cDNA, revealed a single 2.4 Kb RNA band. Mitochondrial aspartate aminotransferase RNA was clearly detected in human kidney, placenta, stomach and spleen as well as in both fetal and adult liver.

Amino Acid Sequence↗

Monoclonal anti-HBs antibodies radioimmunoassay and serum HBV-DNA hybridization as diagnostic tools of HBV infection: relative prevalence among HBsAg-negative alcoholics, patients with chronic hepatitis or hepatocellular carcinomas and blood donors.

Anti-HBs monoclonal antibodies radioimmunoassay (m-RIA) and HBV-DNA hybridization techniques were used to detect HBs antigen (HBsAg)--associated determinants (evidence of HBV on-going infection) and HBV-DNA sequences (evidence of viral multiplication) in the serum samples of 479 patients who were HBsAg negative by standard solid-phase radioimmunoassay. They included 128 alcoholics, 104 patients with chronic hepatitis, fifty-four with an hepatocellular carcinoma, 100 with coagulation disorders and ninety-three blood donors. The aim of this study was the comparison in these populations of the prevalence of the various HBV markers. m-RIA detected HBsAg-associated determinants in 1% of blood donors, 3% of coagulation disorders, 3.1% of the alcoholics, 21.1% of chronic hepatitis and 16.6% of hepatocellular carcinoma; hybridization identified HBV-DNA sequences in 0.9%, 2.2%, 10.9%, 9.6% and 5.5% of these cases, respectively. The combined prevalence of both markers of an on-going HBV infection (with or without viral multiplication) was 14.16%, 26.9% and 22.2% in the latter groups, respectively, as compared with only 3% in patients with coagulation disorders and 2.1% of blood donors. These results confirm the frequency of HBV or HBV-related virus infection in alcoholics, in chronic hepatitis and hepatocellular carcinomas, despite the absence of HBsAg by standard RIA (or even of any other usual marker); this gives further evidence for variations in the expression of HBV infection. A high and quite similar prevalence of usual serum markers and hybridization results was observed in the alcoholics and in the patients with chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatitis B vaccination in chronic alcoholics.

Given the possible role of hepatitis B virus in the occurrence of hepatocellular carcinoma and the high prevalence of HBV infection in alcoholics, we attempted to prevent HBV infection in alcoholic patients with or without cirrhosis. Among 32 cirrhosis, 20 received three injections of hepatitis B vaccine at monthly intervals and 12 had a 4th injection one month later. Effectiveness was evaluated on the anti-HBs titer at the 6th month; it did not differ between the 3- and 4-injection groups. Two patients were good responders (anti-HBs greater than 300 mU/ml), 14 had a low response (m-30 mU/ml at the peak) and 16 (50%) had no detectable anti-HBs. All alcoholics without cirrhosis were given 4 injections; all had detectable anti-HBs but their mean antibody response was 97.7 +/- 4 SD. No obvious statistical difference in the response to the vaccine was noted on the basis of sex or age, or on the discontinuation or not of alcohol intake. Deficient antibody response to vaccines has not previously been demonstrated in patients with cirrhosis or in alcoholics. It remains to be determined whether this response is specific of HBV and how it could be related to the role of HBV in the occurrence of liver alterations in alcoholics.

Adult↗

[Occurrence of increased alpha-fetoprotein in non-neoplastic hepatopathies of alcoholic or non-alcoholic origin].

In order to improve the evaluation of the frequency of alpha-fetoprotein reappearance in non-neoplastic liver disease, we assayed serum alpha-fetoprotein in 251 patients: 134 chronic alcoholics including 7 HBs Ag positive patients, 113 of whom had cirrhosis and 117 patients with chronic active hepatitis, 56 of whom were HBs Ag positive. None of these patients had any signs of hepatocellular carcinoma. Alpha-fetoprotein values above the upper normal limit (much greater than 20 ng/ml) were compared with the type of the liver disease, the serum aminotransferase activity, the usual hepatitis B-virus markers assayed by standard radioimmunology and, in 70 patients, with the results of the HBV-DNA hybridization in the liver. Abnormal alpha-fetoprotein levels were found in only 6.3 p. 100 of patients with HBs Ag negative alcoholic disease and in 17 p. 100 of patients with chronic active hepatitis, without any statistical difference concerning the presence of HBs Ag or not. Alpha-fetoprotein was more often abnormal in subjects who had hypertransaminasemia. For given values of transaminases no statistical relationship between serum alpha-fetoprotein levels and the presence of HBs Ag was observed.

Adult↗

Hepatitis B virus multiplication in the absence of usual serological markers. A study of 146 chronic alcoholics.

The possible role of HBV infection in the progression of alcoholic liver disease remains debated. However, serum HBV markers in alcoholics, although present with a high frequency, mainly consist of anti-HBs and/or anti-HBc antibodies. In order to detect an HBV multiplication that could be missed by the usual markers, we looked for HBV-DNA in the serum of 146 chronic alcoholics; the results were compared with those of the usual serological HBV markers. Sixty-eight of the 146 patients could be studied for HBV-DNA both in the liver and the serum. The 146 alcoholics were divided in 48 with normal liver function (group I); 67 with non-cirrhotic alcoholic liver disease (group II); 31 with alcoholic cirrhosis (group III). Among the 146 patients, 17 had a viral multiplication reflected by serum positive HBV-DNA, as against none of 100 healthy controls (P less than 0.01). Six of the 17 had a normal liver function (6/48 = 12.5%), 7 were of group II (7/67 = 10.4%) and 4 had cirrhosis (4/31 = 12.9%). Serum HBV-DNA was associated with HBsAg in 3 occasions; in addition serum HBV-DNA was also present in 5 HBsAg-negative patients with anti-HBc and/or anti-HBs and even in 9 without any usual HBV marker. The overall prevalence of HBV markers in the 146 patients went from 30.8% to 37.0% when serum HBV-DNA was taken into account; it was similar in the 3 groups studied. Eight patients, of the 68 studied, were liver HBV-DNA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗