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Biomedical subjects

S Erlinger

Publications and source records attributed to S Erlinger.

At least 55 records · Page 3Linked to original sources
PubMed1997

Sequential study of serum glycoprotein fucosylation in acute hepatitis.

BACKGROUND: alpha-Fetoprotein is a useful diagnostic marker in hepatocellular carcinoma, during which its serum level increases and its glycan structure is hyperfucosylated. Normally-expressed glycoproteins (alpha 1-antitrypsin and transferrin) are also hyperfucosylated in hepatocellular carcinoma. alpha-fetoprotein serum levels are also increased in conditions associated with hepatic regeneration, such as acute hepatitis. We conducted a longitudinal study of the alpha 1-6 fucosylation pattern of serum alpha-fetoprotein in ten patients with acute hepatitis and compared it to that of transferrin and alpha 1-antitrypsin. METHODS: Protein levels were measured by using immunochemical assays. Crossed affinoimmunoelectrophoresis in the presence of Lens culinaris agglutinin was performed for each protein, and the fucosylation index, corresponding to the agglutinin reactive fraction, was determined. The results were compared to those in 25 healthy donors and five newborns. RESULTS: alpha-Fetoprotein was hyperfucosylated and remained stable throughout the course of the disease. In contrast, serum transferrin and alpha 1-antitrypsin gradually became hyperfucosylated during the course of acute hepatitis. The transferrin and alpha 1-antitrypsin fucosylation indexes correlated with each other, but not with the alpha-fetoprotein fucosylation index. No correlation was found between alpha-fetoprotein, alpha 1-antitrypsin and transferrin fucosylation indexes and the corresponding glycoprotein serum levels. CONCLUSIONS: Hyperfucosylation of alpha-fetoprotein is not specific to hepatocellular carcinoma. Increased alpha 1-6 fucosylation should not be considered solely as a tumour marker, but might also reflect cell proliferation. The study of alpha 1-6 hyperfucosylation process of normally-expressed glycoproteins awaits further investigation, to test its usefulness as a new marker of liver regeneration during the follow-up of acute hepatitis.

Acute Disease↗
PubMed1997

Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation.

BACKGROUND/AIMS: In rats with cholestasis due to bile duct ligation, the expression of the Na+-dependent taurocholate co-transporting polypeptide, the major uptake system for conjugated bile acids in hepatocytes, is down-regulated. Our purpose was to examine the expression of the organic anion transporting polypeptide, a Na+-independent uptake system for bile acids and organic anions, in rats with bile duct ligation, and to compare the expression of organic anion transporting polypeptide to that of Na+-dependent taurocholate co-transporting polypeptide. METHODS: Rats with bile duct ligation were studied after 1, 3 or 7 days. The expression of organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide proteins was examined by Western blot analysis and steady-state mRNA levels were determined by Northern blot analysis using cDNAs encoding organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide. Sham-operated animals were used as controls. RESULTS: The expression of organic anion transporting polypeptide protein was slightly, but not significantly, decreased 1 day after ligation (10.3%); it was markedly decreased after 3 days (56.9%; p<0.03) and 7 days (46.8%; p<0.05) compared to sham-operated animals. Steady-state mRNA levels of organic anion transporting polypeptide were decreased by 79.7% (p<0.04), 48.8% (p<0.02) and 57.4% (p<0.02) after 1, 3 and 7 days respectively. For comparison, Na+-dependent taurocholate co-transporting polypeptide protein and mRNA levels were decreased by 73.8% (p<0.03) and 70.0% (p<0.05) at 1 day and remained low after 3 and 7 days. CONCLUSIONS: In rats with bile duct ligation, the expression of organic anion transporting polypeptide protein and mRNA is down-regulated. Down-regulation of organic anion transporting polypeptide seems less pronounced than that of Na+-dependent taurocholate co-transporting polypeptide. Nevertheless, it could contribute to a decreased uptake of potentially toxic bile acids or organic anions in this situation.

Animals↗
PubMed1997

Acute hepatitis induced by alpha-interferon, associated with viral clearance, in chronic hepatitis C.

We describe the cases of two patients with chronic hepatitis C who developed acute hepatitis with marked amino-transferase elevations and jaundice 3 and 5 months after initiation of interferon treatment. Hepatitis resolved rapidly after cessation of interferon. No autoantibodies were detected. Hepatitis was followed by viral clearance, demonstrated by clearance of hepatitis C viraemia. We propose that hepatitis may be due to an immune lysis of hepatocytes and suggest that this immune response may contribute to viral clearance.

Acute Disease↗
PubMed1997

Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg.

BACKGROUND/AIMS: The persistence of serum and liver hepatitis B virus (HBV) sequences in patients with chronic hepatitis B after loss of HBsAg has already been described. We have attempted to elucidate the significance of these HBV sequences after loss of HBsAg. METHODS: Fifteen patients were studied. We looked for serum and liver HBV DNA, using polymerase chain reaction (PCR) with different sets of primers and in situ hybridization. The sedimentation velocity of serum HBV DNA was measured on a gradient of sucrose in two patients. RESULTS: Serum HBV DNA was detected by PCR in four of the 14 patients tested at 0 months after loss of HBsAg, two patients remained HBV DNA positive until 12 months, and none was positive at 24 months. The sedimentation velocity of serum HBV DNA in sucrose was relatively similar to that of a chronic HBV carrier with active viral replication. Liver HBV DNA was demonstrated by PCR in all 15 patients and by in situ hybridization in six patients. CONCLUSIONS: Our results show that: 1) HBV DNA may persist in the serum in a minority of patients and may be associated with circulating viral particles; 2) HBV DNA persists in the liver in all patients and its extrachromosomal localization was shown by in situ hybridization technique in some cases. These results suggest the persistence of low-level HBV replication after loss of HBsAg.

Adult↗
PubMed1997

Acute hepatitis caused by alverine associated with anti-lamin A and C autoantibodies.

We report the case of a 67-year-old woman in whom onset and regression of acute hepatitis were closely related to the time of administration and withdrawal of the smooth muscle relaxant alverine. Antinuclear antibodies were positive, and their titer followed the course of hepatitis. They presented a smooth rim-like nuclear immunofluorescence staining pattern. Immunoblot assay showed that they were directed against lamin A and lamin C. This suggests that alverine should be added to the list of drugs known to produce acute hepatitis, and that drug-induced liver injury is a possible cause of antinuclear antibodies specific for lamin A and lamin C.

Acute Disease↗
PubMed1997

Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients.

BACKGROUND/AIMS: A 4977-base pair deletion has been detected in the hepatic mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion ascribed to impaired mitochondrial beta-oxidation. However, only a single deletion had been looked for in this previous study, and it could not be determined whether the deletion was preexisting or acquired. Alcohol abuse increases the formation of reactive oxygen species in hepatic mitochondria. If this effect accelerates the oxidative aging of mitochondrial DNA, several other mutations would be expected. METHODS: The mtDNA region extending from nucleotide 8167 to nucleotide 14246 was screened for the presence of large mitochondrial DNA deletions in 58 alcoholic patients and 67 age-matched non-alcoholic controls. Hepatic DNA was subjected to polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively, and the boundaries of the mitochondrial DNA deletions were sequenced. RESULTS: Only 3% of the non-alcoholic controls carried a mitochondrial DNA deletion, whereas 24% of all alcoholic patients and 85% of the 13 alcoholic patients with microvesicular steatosis exhibited either single or multiple 4977, 5385, 5039 and 5556-base pair mitochondrial DNA deletions. No deletion(s) were observed, however, in 13 patients with microvesicular steatosis due to other causes. CONCLUSIONS: Diverse mitochondrial DNA rearrangements are observed in alcoholic patients with microvesicular steatosis. We suggest that alcohol abuse leads to premature oxidative aging of mitochondrial DNA. Hypothetically, oxidative damage to mitochondrial constituents (DNA, proteins and lipids) may favor microvesicular fat deposition.

Adult↗
PubMed1997

Subfulminant syncytial giant cell hepatitis: recurrence after liver transplantation treated with ribavirin.

We report the case of an adult patient affected by acute syncytial giant cell hepatitis which had a subfulminant course leading to liver transplantation. Syncytial giant cell hepatitis recurred after transplantation and was efficiently treated with ribavirin. In this patient, the recurrence of the disease, the presence of filamentous strands on electron microscopy during both bouts of hepatitis and the efficacy of ribavirin on post-transplantation hepatitis suggest that the disease was caused by an original virus. This observation also suggests that early administration of ribavirin in patients affected by acute syncytia; giant cell hepatitis of unknown origin could avoid liver transplantation.

Acute Disease↗
PubMed1997

Drug-induced cholestasis.

Drug-induced cholestasis may be due to impairment of hepatocellular bile secretion (pure cholestasis or cholestatic hepatitis), obstruction of ductules (cholangiolitis) or interlobular ducts (cholangitis), or extrahepatic obstruction (sclerosing cholangitis). Mechanisms of hepatocellular cholestasis are multiple and include inhibition of various transport systems, cytoskeleton poisoning, disturbed intracellular calcium homeostasis and increased permeability with regurgitation of bile constituents into plasma. Pure hepatocellular cholestasis is mostly observed with sex steroid hormones and anabolic steroids. Ductular or ductal cholestasis (drug-induced cholangiopathy) may be acute and self-limited, or prolonged with ductopenia, occasionally leading to biliary cirrhosis. An immune mechanism has been proposed. Sclerosing cholangitis with strictures near the confluent of hepatic ducts is observed after intraarterial administration of floxuridine for chemotherapy of hepatic metastases. Some drugs may induce the formation of cholesterol gallstones, or precipitate in bile and form biliary sludge or stones in the gallbladder or common bile duct.

Animals↗
PubMed1997

Premature oxidative aging of hepatic mitochondrial DNA in Wilson's disease.

BACKGROUND & AIMS: Aging is associated with and may be caused by acquired somatic mutations of the mitochondrial genome. In Wilson's disease, inherited mutations of a nuclear gene encoding a copper transporter cause accumulation of copper in the liver, particularly within mitochondria. Because copper has prooxidant properties and the mitochondrial genome is particularly susceptible to oxidative damage, we hypothesized that Wilson's disease may cause premature oxidative aging of mitochondrial DNA. METHODS: Hepatic DNA was screened for large mitochondrial DNA deletion(s) in 16 patients with Wilson's disease and 67 control subjects. Deleted mitochondrial DNA copies were amplified by polymerase chain reaction and were sequenced. RESULTS: Although 15 of the 16 patients with Wilson's disease were 30 years old or younger, 8 of them (50%), including the 6 patients with cirrhosis (100%), had diverse mitochondrial DNA deletions, whereas only 2 controls (3%), aged 39 and 45 years, showed a mitochondrial DNA deletion. CONCLUSIONS: Wilson's disease is associated with frequent, diverse, and early deletions of mitochondrial DNA. Accumulation of prooxidant copper within hepatic mitochondria may cause this premature oxidative aging of mitochondrial DNA. Thus, inherited mutations of a nuclear gene may cause somatic mutations of the mitochondrial genome in this condition.

Adolescent↗
PubMed1997

Early negative tests for serum HCV RNA as a predictor of sustained response to interferon therapy in patients with chronic hepatitis C.

In patients with chronic hepatitis C, the main predictors, before treatment, of sustained response to interferon therapy are serum hepatitis C virus (HCV) RNA level and HCV genotype. During treatment, early response with normalization of serum alanine aminotransferase (ALT) and negative tests for serum HCV RNA are predictive of a sustained response. In the absence of early response observed within the first three months of therapy, the chance of sustained response is very low and interruption of interferon therapy may be considered.

Alanine Transaminase↗
PubMed1997

Prolonged interferon-alpha therapy of hepatitis B virus-related decompensated cirrhosis.

Interferon alpha therapy of hepatitis B virus-related decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3-48 months) low-dose (3 million units) IFN-alpha therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5-7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-alpha therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.

Adult↗
PubMed1997

Incidence of dysthyroidism during interferon therapy in chronic hepatitis C.

Seventy-nine patients (40 males, 39 females) were enrolled in a prospective study of lymphoblastoid interferon-alpha (IFN), 3-5 MU three times weekly. They were randomly assigned to receive either 12 months of IFN therapy, or to 6 months of observation followed by 6 months of IFN therapy. The thyroid functional and immunological status was checked every other month during and after treatment. Before treatment, antithyroid antibodies were found in 6 patients (7.5%). Two were hypothyroid and were excluded from the study before starting IFN therapy. Seventy-seven patients received IFN therapy. Of these, thyroid abnormalities appeared in 6 (7.5%). Hyperthyroidism was observed in 3 patients. Two recovered within a few months, but 1 developed subsequent hypothyroidism. Hypothyroidism was observed in 2 patients. TSH blood values were persistently abnormal, but thyroid antibody levels remained increased and fluctuating. Thyroid function usually recovered within a few months; but 2 patients required hormonal therapy and 1 was treated with carbimazole. In 1 patient, a small thyroid papillary carcinoma was observed, but no evidence of relationship with the liver disease or with IFN therapy was found. In a patient with chronic hepatitis C, systematic thyroid assessment should be performed before initiating IFN therapy, including clinical examination, and measurement of TSH and anti-thyroperoxidase antibodies (TPO Ab). During treatment, a TSH assay every other month appears to be necessary and sufficient.

Adult↗
PubMed1997

[Effects of micronized natural progesterone on the liver during the third trimester of pregnancy].

In France, prescription of micronized progesterone at high doses of 900 to 1200 mg/day is common practice in the case of preterm delivery, even though this is neither an indication nor a posology given for marketing authorisation. A few cases of gestational pruritus have been reported during such use, associated with cholestasic and/or cytolytic hepatic disorders. We report here the results of a controlled, double-blind study versus a placebo, aimed at assessing the effects on the liver of micronized progesterone administered orally at high doses (900-1200 mg/day), conducted in a population of 201 women presenting moderate menace of preterm delivery during the third trimester of pregnancy. 85 patients received micronized progesterone and 116 the placebo. The increase above normal levels of total biliary acids (TBA) and aminotransferases (ASAT, ALAT), was significantly more frequent in the micronized progesterone than in the placebo group. Among the 26 patients (14%) with a level of TBA superior to 10 mumoles/l during treatment, 18 belonged to the progesterone and 8 to the placebo group (p = 0.004); the 6 patients (3.4%) with increased ASAT were all under micronized progesterone (p < 0.001), as were the 10 patients (5.6%) with increased ALAT (p < 0.001). However, there is no statistically significant difference between the two groups regarding the occurrence of clinical manifestations (icterus, pruritus) which could be attributed to gravid cholestasis. We may conclude from this prospective study that, during the third trimester of pregnancy, micronized progesterone is associated with a significant risk of biological cholestasis. This would suggest that in patients genetically predisposed towards gravid cholestasis, micronized progesterone could be a factor favoursing this disease.

Adult↗
PubMed1997

[Ultrasonographic anomalies of intrahepatic biliary ducts: contribution of the comet-tail image].

OBJECTIVES: The aim of this study was to evaluate the sensitivity and specificity of the ultrasound intrahepatic bile duct wall comet-tail artifact for the diagnosis of biliary disease. METHODS: All subjects who underwent upper abdominal ultrasound examination were included in the study over an 18-month period. The presence or absence of the comet-tail artifact (that is hyperechoic pattern with several parallels lines, constant, lining on the intrahepatic biliary ducts) was noted. RESULTS: Fourteen thousand four hundred and ninety-eight patients were included. The comet-tail artifact was only found in 10 of the 14 211 patients without biliary tract disease (99.9% specificity), but in 35 of the 287 patients with biliary disease (12.2% sensitivity). The positive predictive value for the diagnosis of biliary tract disease was 77.7%. The artifact was associated with an angiocholitis in 83% of the patients. CONCLUSION: Despite its low sensitivity, the sonographic comet-tail artifact of the intrahepatic bile duct wall was strongly correlated with the presence of biliary disease. This artifact may be related to an enlargement of the bile duct wall.

Bile Duct Diseases↗
PubMed1996

Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis.

Disruption of the murine mdr2 (multidrug-resistance) gene, which encodes a phosphatidylcholine flippase, leads to a hepatic disorder because of loss of biliary phospholipid secretion. Among the hereditary human cholestasis, a subtype of progressive familial intrahepatic cholestasis with high gamma-glutamyltranspeptidase (GGT) serum activity shares histological, biochemical, and genetic features with mice lacking mdr2 gene expression (mdr2 -/- mice). No MDR3 (human mdr2 homolog) messenger RNA (mRNA) was detected by Northern blotting in the liver of a patient suffering from this form of PFIC, and the biliary phospholipid level in a second patient was substantially decreased. Thus, the absence of the MDR3 P-glycoprotein may be responsible for this type of PFIC, which, as in the murine model, may be due to a toxic effect of bile acids on the biliary epithelium in absence of biliary phospholipids.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

Interferon-alpha therapy for chronic hepatitis C in special patient populations.

Interferon-alpha therapy for chronic hepatitis C in special patient populations raises a number of issues. Patients with hemophilia, kidney disease requiring hemodialysis, mixed cryoglobulinemia, HIV infection, and those receiving an allograft share some characteristics that complicate the treatment of hepatitis C virus infections. These patients generally have some degree of immune deficiency, higher levels of hepatitis C virus replication, and are infected with genotypes 1a or 1b. Each of these characteristics is often associated with a poor response to interferon therapy. Clinical research in this area also has been limited. Current data and clinical experience demonstrate that interferon-alpha therapy should be considered in patients with hemophilia who have concurrent hepatitis C viral infection. Other hepatitis C virus-infected patient populations in which interferon-alpha therapy may be beneficial include those undergoing hemodialysis, mixed cryoglobulinemia, or HIV infection. Further, the high incidence of relapse following treatment cessation in these patients warrants prolonged administration of interferon-alpha. Patients undergoing renal or hepatic allograft transplantation who develop hepatitis C virus infections are not as likely to benefit from interferon-alpha therapy. These patients may be at risk for allograft rejection during interferon treatment.

Chronic Disease↗