[Diagnostic strategy when confronted with a moderate and prolonged increase of transaminases]. / Démarche diagnostique devant une augmentation modérée et prolongée des transaminases.

TWO TYPES OF SITUATIONS: Measurement of transaminase serum activity is a common biological test. Although the etiological scope of acute and severe hyper-aminotransferase is codified and limited, that of prolonged and moderate hyper-aminotransferase is much broader. IN THE CASE OF PROLONGED AND MODERATE INCREASE IN TRANSAMINASE SERUM ACTIVITY: The discovery of this abnormality during systematic biological controls is a frequent situation, and its management is relatively well standardised. It requires a rigorous diagnostic strategy, which includes the search for consumption of alcohol, overweight, chronic hepatic disease of viral origin and the nature of the medicinal products ingested. FROM AN ETIOLOGICAL POINT OF VIEW: The most frequent causes of moderate and prolonged hyper-aminotransferase are alcohol abuse, overweight, non-insulin-dependent diabetes, dyslipaemia, viral hepatitis and medicinal products. However, less frequent hepatic or extra-hepatic causes must not be neglected.

[Hepatic disorders related to Lyme disease. Study of two cases and a review of the literature]. / L'atteinte hépatique dans la maladie de Lyme. Etude de deux cas et revue de la littérature.

We report two cases of Lyme disease, revealed by hepatic damage in a 71- and a 59-year old man. In the first case, the disease was revealed by febrile jaundice whereas, in the second case, results of liver tests showed cytolytic and cholestatic abnormalities with fever. Lyme disease is a zoonosis due to infection by Borrelia burdorferi transmitted by ticks. The multiple phases of the disease explain the polymorphism of the clinical manifestations. Usually, extrahepatic symptoms are first observed, including neurological tropisms of Borrelia burdorferi. On the contrary, hepatic impairment due to Lyme disease is rare, often asymptomatic and with biological manifestations only.

Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.

BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.

[Epidemiology and natural history of cholelithiasis]. / Epidémiologie et histoire naturelle de la lithiase biliaire.

Gallstone disease is relatively common, affecting approximately 15% of the population in Europe and North America, but it is benign since its natural history remains asymptomatic in nearly 80% of cases. The stones are predominantly cholesterol derived in 80% and pigmentary in 20% of cases. Recent epidemiologic studies using ultrasound examination have determined the factors favouring lithogenesis, in addition to those that are already wellknown, such as age, obesity, female gender, high blood triglyceride levels and multiparity, the risk is correlated with high, frequent variations in weight, with intake of certain drugs and with alimentary habits. In addition, physical exercise plays a protective role against the development of symptomatic gallstone disease.

[Portal hypertension caused by intra-hepatic block during chronic lymphoid leukemia]. / Hypertension portale par bloc intra-hépatique au cours d'une leucémie lymphoïde chronique.

Portal hypertension in chronic lymphocytic leukemia is rare. A 66 year-old man was admitted for splenomegaly, thrombopenia and cholestasis. Endoscopy showed esophageal varices. The hepatic venous pressure gradient was 15 mmHg. The liver biopsy showed dense leukemia cells in sinusoidal and portal sites. After splenectomy, the hepatic venous pressure gradient normalized, but esophageal varices and cholestasis persisted. The authors discuss the mechanisms of portal hypertension in chronic lymphocytic leukemia. Previously reported cases are summarized.

[Percutaneous cholecystostomy. A study of 30 patients]. / Cholécystostomie percutanée. Une étude chez 30 malades.

OBJECTIVE AND METHODS: The treatment of acute cholecystitis or angiocholitis is often difficult in elderly or very ill patients. The aim of this retrospective study was to assess the efficacy and the results of ultrasound guided percutaneous cholecystostomy in patients with acute cholecystitis or biliary tract obstruction and anesthetic or surgical contraindications. RESULTS: Thirty patients (25-93 years, 16 men and 14 women) were included in this study. Ultrasound guided percutaneous cholecystostomy was successful on the septic syndrome in 27 patients; endoscopic sphincterotomy was performed in 6 patients after clinical improvement. A failure of the procedure on sepsis was observed in 3 patients: cholecystectomy was performed after cardiac improvement in one patient, and 2 patients died. Two other patients died of extradigestive diseases. No serious complication related to cholecystostomy was observed. CONCLUSION: Ultrasound guided percutaneous cholecystostomy is a safe and simple procedure. It can be done at bedside and has low morbidity and mortality. It can be considered as a definitive treatment, or a temporary one with secondary surgical or endoscopic management.

[Adult idiopathic ductopenia. 1 case]. / Ductopénie idiopathique de l'adulte. Un cas.

Idiopathic adult ductopenia is very rare. We report one case in a 30-year-old man, whose clinical course was characterized by jaundice and pruritus. Laboratory investigations revealed cholestasis and polyclonal hypergammaglobulinemia. Serum antinuclear, antimitochondrial, and anti-smooth muscle antibodies and serological markers for viral hepatitis were negative. Endoscopic retrograde cholangiography showed no liver or biliary tract abnormalities. Histological examination of a liver specimen showed a vanishing bile duct syndrome and moderate portal infiltration with lympho-histiocytic cells; there were no granulomas. Liver transplantation was performed due to rapid development of cirrhosis. The differential diagnosis of idiopathic adult ductopenia with small duct primary sclerosing cholangitis, auto-immune cholangiopathy, and non syndromic paucity of intrahepatic bile ducts is unclear.

[Duodenal hematoma, acute pancreatitis, and hemoperitoneum after endoscopic hemostasis for duodenal ulcer]. / Hématome duodénal, pancréatite aiguë et hémopéritoine après hémostase endoscopique d'un ulcère duodénal.

Therapeutic endoscopy is followed by complications in less than 5% of cases. We report a case of an intramural duodenal hematoma after local endoscopic injection of 28 mL of adrenaline 1/10,000 for a bleeding duodenal peptic ulcer. This hematoma was associated with acute pancreatitis and was revealed by a hemoperitoneum.

Amplification and detection of the terminal 3' non-coding region of hepatitis C virus isolates.

A reverse transcription polymerase chain reaction (RT-PCR) assay was set up to amplify, from chronically infected patients, the recently discovered hepatitis C virus (HCV) 3'non-coding region (3'NCR). A panel of 149 samples was tested by RT-PCR for the 3'NCR. Two detection methods of amplified products were evaluated: ethidium bromide staining on 3% agarose gel electrophoresis and DNA enzyme immunoassay ("DEIA"). Results were compared with those obtained by amplification of the 5' non-coding region (5'NCR), i.e. the "Amplicor" HCV RNA qualitative assay. Genotype distribution of the 86 Amplicor-positive samples was subtype 1a: n = 15 (17.4%); subtype 1b: n = 32 (37.2%); subtype 2a/2c: n = 7 (8.1%); type 3: n = 25 (29%); type 4: n = 2 (2.3%); type 5: n = 1 (1.2%); not determined: n = 4 (2.3%). Sixty-three sera were HCV RNA-Amplicor-negative, 32 of which were from HCV-seronegative patients and 31 from HCV-seropositive patients. All seronegative samples were negative by both PCR methods. None of the Amplicor-negative samples from seropositive patients were positive by the 3'NCR assay. Forty-seven (54.7%) and 83 (96.5%) of the 86 Amplicor-HCV-RNA-positive samples were positive after ethidium bromide staining and by the 3'NCR assay using DEIA, respectively. The limit of detection by end-point dilution was lower with Amplicor. No difference between genotypes was detected for the 3'NCR RT-PCR, and a high degree of concordance was obtained between the Amplicor and the 3'NCR DEIA results (97.4%). Nevertheless, further studies are needed before the 3'NCR RT-PCR assay could be used instead of the 5'NCR RT-PCR for diagnostic purposes.

Hepatic nodules as single organ involvement in an adult with Langerhans cell granulomatosis. A case report.

Liver involvement manifesting as hepatomegaly in Langerhans cell granulomatosis (LCG) is well known, but the definitive diagnosis is generally possible because other organs are involved. We report a 41-year-old white man who presented with cholestasis and liver nodules as an isolated hepatic LCG. The diagnosis of LCG was suspected based on routine histopathologic examination; the diagnosis became definitive 4 years later when Birbeck granules were found in the liver, an uncommon occurrence in this organ. This is an unusual presentation of a benign form of this disease and one of the first that reported Birbeck granules in the liver.

Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence do not predict the response to recombinant interferon-alfa therapy in French patients.

BACKGROUND/AIMS: Studies of HCV quasispecies during interferon treatment have shown the selection of resistant clones. Enomoto et al. have defined the interferon sensitivity-determining region in an amino acid stretch of the HCV-1b NS5A region. Patients with a mutant strain before treatment were complete responders, whereas those with wild-type HCV-J strain were resistant to interferon. The same region was studied in HCV isolates of French patients. METHODS: Forty-three HCV-1b chronically infected patients, consisting of 26 non-responders and 17 complete responders to interferon-alfa treatment (3 MUI tiw for 6 months), were included retrospectively. We directly sequenced the NS5A(2209-2248) HCV region of these patients before treatment. The viral load could be obtained from six complete responders and 15 non-responders. RESULTS: We detected wild-type and intermediate strains, but only two mutant strains were present. One of them was found in a non-responder. In three complete responders, we found a wild-type strain. The distribution of the various strains was rather different from that found in Japan. Before treatment, the viral load was lower in complete responders (p=0.01). CONCLUSIONS: Only two mutant strains were detected in our study. This could partially explain the low response rate to interferon treatment of French HCV-1b-infected patients, although the dose regimen was lower than in Japanese studies. Also, wild-type strains were found in some complete responders, and no correlation was determined between the mutation number in the NS5A(2209-2248) region and response to alfa interferon therapy. This may be related to epidemiological differences between HCV-1b strains present in France and those in Japan. Searching for the mutant NS5A pattern before treatment does not appear to be useful in French patients as it is too uncommon.

Direct blotting electrophoresis for sequencing and genotyping hepatitis C virus.

Many methods have been used to differentiate the hepatitis C virus (HCV) genotypes based on, for example, type specific primers, probes and restriction fragment length polymorphism. However, determination of the nucleotide sequence remains the reference. Therefore, a simple non-radioactive cycle sequencing technique was developed for clinical tests. PCR-amplified products of the 5' non-coding region (from position -274 to -31) were sequenced using a 5' digoxygenin-labeled primer. After denaturation, the samples were loaded on a direct blotting electrophoresis system (GATC 1500). Sequencing products were blotted onto a nylon membrane during the electrophoresis. The DNA fragments were then UV-cross-linked, incubated with phosphatase-labeled anti-digoxygenin antibody and stained with a precipitating substrate. Reading the sequence of six samples were possible within 2 days. In 41 different samples, five different genotypes were found by sequence analysis from position -245 to -69, of which 17 were type 1a, 7 type 1b, 5 type 2a, 8 type 3a, 3 type 4 and 1 type 5. These results agreed with those obtained by reverse hybridization assay. Direct blotting electrophoresis offered a good non-radioactive method of performing clinical sequencing on a medium scale, with a minimum of investment.

[Chemical colitis caused by glutaraldehyde]. / Colite chimique au glutaraldéhyde.

Glutaraldehyde disinfectant solution may be a cause of toxic chemical colitis. We report two cases. Ultrasonic features were studied in one case and mimic colonic ischemia, inflammatory and/or infectious colitis. These findings were colonic wall thickening especially mucosal (hypoechogenicity) and submucosal (hyperechogenicity) layers. This diagnosis should be discussed when one sees a patient with echographic findings of acute left-sided colitis just after uncomplicated colonic endoscopy.

Cirrhosis: a new, but expected cause of biliary sludge.

BACKGROUND/AIMS: Biliary sludge is increasingly recognized as a natural stage in gallstone formation. Logically, cirrhosis, a well-documented cause of black pigment cholelithiasis, should be another condition predisposing to the development of sludge. The aim of this study was to assess the prevalence of biliary sludge in an unselected population and to test the hypothesis that cirrhosis could be one of the causes of sludge. METHODS: We reviewed the clinical findings and ultrasonograms of 2138 patients, hospitalized or not, consecutively seen in our department between January 1993 and December 1994. Sonograms showing biliary sludge mixed with stones were excluded. Three hundred and eighty-eight of the 2138 were cirrhotic patients. RESULTS: The overall prevalence of biliary sludge was 4%. Sludge was found in 44 of 388 (11%) of the cirrhotic patients (alcoholism, n = 39; chronic viral B hepatitis, n = 3; hemochromatosis, n = 1; and cryptogenic, n = 1), compared with 42 of 1750 (2%) noncirrhotic patients (p < 0.000001). Thirteen cirrhotic patients received intravenous alimentation for 2 to 17 days, 8 were given somatostatin for variceal bleeding, and 7 have previously had 1 to 5 sessions of endoscopic sclerotherapy of esophageal varices with polidocanol. CONCLUSIONS: This study convincingly demonstrates that cirrhosis must be added to the growing list of conditions associated with biliary sludge.

[Research of type 1, 2 and 3 hepatitis C virus specific antibodies in relation to the viral genotype in chronically infected patients]. / Recherche des anticorps spécifiques des types 1, 2 et 3 du virus de l'hépatite C en relation avec le génotype viral chez des patients chroniquement infectés.

The determination of the viral genotype in chronically HCV infected patients is used as an epidemiologic tool, a predictive marker of the evolution of the disease and especially of the response to the interferon alfa therapy. Its determination needs an amplification of the selected genomic region and remains expensive. Thus an indirect determination of the genotype has been proposed using the characterization of type-specific antibodies. In 101 chronically HCV infected patients, a serologic method specific for HCV type 1, 2 and 3 has been evaluated in relation to the genotyping one. The test was interpretable in 64 sera and in agreement with the genotyping method in 92% of the samples. The reactivity of the test was lower in hemodialysis and IVDUs patients (p < 0.02). The mixed results obtained by the serologic typing method were not in agreement with the results of the genotyping coinfections. We could not differentiate the possible past infections from the cross-reactivities of the test. The serotyping methods was simple and rapid, allowing generally a deduction of the viral genotype. It could be an attractive approach if the reactivity was improved and the subtyping was possible.

[Seroprevalence of viral hepatitis A in at the Amiens University Hospital]. / Séroprévalence de l'hépatite virale A au CHU d'Amiens.

OBJECTIVES AND METHODS: The epidemiology of viral hepatitis A has been evolved in the past few years, resulting in an increasing number of people without immunity to this virus. Health care workers are usually considered to be a group at risk of contamination by hepatitis A. A sero-epidemiologic study was performed in 525 members of the Pediatry, Gastroenterology, Internal medicine, Digestive radiology, kitchen and maintenance department staffs in the Amiens University Hospital. The aim of this study was to describe the epidemiology of hepatitis A and to estimate the level of occupational hazard it represents in the hospital. RESULTS: Age, low education level, country of origin in an endemic region and more than 2 siblings or children were significantly associated with the presence of anti-HAV antibodies. The prevalence of 50% was similar to that observed in other hospitals, but lower than that found in the general population. Seroprevalence was not higher in departments exposed to stools (Pediatry, Digestive endoscopy and laboratories) than in others. A higher rate of seroprevalence was observed in kitchen and maintenance staffs than in medical, laboratory and Radiology staffs, in Internal medicine than in the Gastroenterology Department, and in the laboratory than in Radiology Department. These differences disappeared after adjustment for extraprofessional parameters which appeared to be most important for hepatitis A epidemiology. CONCLUSIONS: The hospital occupational hazard for hepatitis A virus did not seem higher than that observed in the general population.