Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

Acetylation polymorphism expression in patients before and after liver transplantation: influence of host/graft genotypes.

The consequences of liver transplantation on NAT2 activity were studied in 58 patients of Caucasian origin and compared with a group control of 119 unrelated healthy individuals of the same ethnic origin. Acetylation phenotypes were determined using caffeine as a probe drug before and repeatedly after liver transplantation. NAT2 genotypes were determined with three separate polymerase chain reactions to detect either the NAT2*4 wild-type allele or the NAT2*5A, NAT2*6A and NAT2*7A mutated alleles, associated with a decrease in NAT2 enzyme activity. In patients, the molar urinary elimination ratio AFMU/(AFMU+1X+1U) appeared more reliable than AFMU/1X for assessing the acetylation phenotype and fitted better with the various haplotypes. The variation of xanthine oxidase activity as measured by the 1U/1X urinary elimination ratio, appeared to be responsible for the poor phenotype prediction from the AFMU/1X ratio in post-transplanted patients. Regardless of the pathologic conditions of the treatment in progress, the genotype of the liver played an overwhelming role in the phenotypic expression of NAT2 compared with the genotype of other organs, where NAT2 was expressed in patients who presented a chimerism after liver transplantation.

Mycophenolate mofetil-induced villous atrophy.

Mycophenolate mofetil (MMF) is a new immunosuppressant developed for the prevention and treatment of acute renal rejection after transplantation. Diarrhea is the most frequent side effect observed during treatment with MMF. Its pathogenic mechanisms remain unknown. We describe a case of severe diarrhea due to villous atrophy in a renal transplant recipient during treatment with MMF. The patient was free of symptoms before MMF. Villous atrophy disappeared a few months after MMF withdrawal.

Direct in situ reverse transcriptase-linked polymerase chain reaction with biotinylated primers for the detection of hepatitis C virus RNA in liver biopsies.

To assess the presence and the cellular distribution of hepatitis C virus (HCV) RNA in the liver of 11 patients with confirmed HCV infection, a direct in situ reverse transcriptase-linked polymerase chain reaction (RT-PCR) method was performed on formalin-fixed and paraffin-embedded biopsies. The oligonucleotide primers used were specific to the 5' non coding region. An unlabelled downstream oligonucleotide served as a primer for reverse transcription as well as PCR. The upstream oligonucleotide serving as a primer for PCR was biotinylated, allowing a direct enzymatic detection of PCR products. HCV infected cells revealed cytoplasmic staining mainly concentrated towards the interface of the nucleus and cytoplasm. Most of the stained cells were hepatocytes and sometimes Kupffer cells. The results were compared with those obtained by RT-PCR of RNA extracted from the corresponding tissue block. Extracted HCV RNA could be detected in liver tissues of nine out of 11 (82%) infected patients. The detection rate using in situ RT-PCR was 7/11 (63%). The use of labelled primers improved specificity of direct in situ methods, by preventing non-specific incorporation of labelled dNTPs into fragmented DNA. Further studies are however required in order to increase detection sensitivity of HCV infection by in situ molecular methods.

Seroepidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis.

In a serologic survey for Echinococcus multilocularis infection, we screened sera from 7,884 subjects from the Doubs Departement in France, an area endemic for alveolar echinococcosis (AE) of the liver. An enzyme-linked immunosorbent assay (ELISA) with a highly species-specific antigen (Em2) and an E. multilocularis crude antigen (Emc) was used for screening. An evaluation of the cost/benefit relationship of this screening, followed by therapeutic management of patients, was made and compared with the actual cost of the follow-up and treatment of the disease in symptomatic cases in this endemic area. Antibody reactions to Em2 and/or Emc made possible the detection of eight asymptomatic clinical cases (seroprevalence averaging 1/1,000), with typical lesions of active AE revealed by abdominal ultrasonography and computed tomography. All were seropositive using the Emc ELISA but two were seronegative using the Em2 ELISA. In five additional seropositive cases, the radiologic investigations revealed small calcified lesions similar to the lesions of abortive AE previously found in Alaska. The cost of this serologic screening program per screened subject and per diagnosed case averaged 50.00 French Francs (FF) (U.S. $8.60) and 60,000.00 FF (U.S. $10,909.00), respectively. The cost of diagnosis, follow-up and treatment of the patients was 5,086.00 FF (U.S. $929.00) per patient per month in the case of diseases diagnosed by the screening program and 7,086.00 FF (U.S. $1,288.00) per patient per month for patients with symptomatic AE. This survey indicates a high prevalence of AE in the target area; it confirms the long latency period of the larval growth in human AE and shows that abortive AE is present in Europe. The use of both the Emc and Em2 ELISAs seems to be better than using the Em2 ELISA alone. The cost of the hospitalization and treatment of the eight screened patients would appear to be relatively high. Even though two of them were asymptomatic, they had very severe forms of the disease. In fact, the total cost was much lower than the actual cost of the disease when diagnosed from clinical symptoms.

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization.

Only limited data are available on comparative genomic hybridization (CGH) in hepatocellular carcinoma (HCC). They concern mainly B virus related HCC. Therefore, we used CGH to detect chromosomal imbalances in 16 non-B virus related HCC in alcoholic cirrhosis in 7 cases (HA1 to HA7), in C virus cirrhosis in 7 cases (HC1 to HC7), in non-cirrhotic liver in 2 cases (NC1, NC2), and in 9 non-malignant cirrhotic tissues. The most frequent imbalances in HCC were gains of whole chromosomes or chromosomal regions 7 or 7q (10/16, 62%), 1q (9/16, 56%), 5 or 5q (9/16, 56%), 8q (8/16, 50%), 6p (6/16, 37%), 15q (5/16, 31%), 20 or 20q (5/16, 31%), and losses of 17p (6/16, 37%), and 8p (5/16, 31%). High-level gains were identified in HCC on 1q (2/16), 3q (1/16), 7q (1/16), and 8q (3/16). No chromosomal imbalances were detected in any of the cirrhotic tissues. Most of the gains, losses, and amplifications detected in this CGH study corresponded well to those identified in previous studies, except for gains of whole chromosome 5 or 7 and/or of chromosome arms 5q or 7q and losses on 4q. Our results suggest that other chromosomal regions are involved in hepatocarcinogenesis.

Soluble IL-2-receptor and CD8 in the serum and the periparasitic granuloma of patients with alveolar echinococcosis.

Cellular immunity plays a key role in the defence against the larva of the cestode Echinococcus multilocularis. This larva is responsible for alveolar echinococcosis (AE) of the liver, a rare parasitic disease which occurs in endemic areas including European alpine countries, Alaska, the USSR, Western China and Northern Japan. We have shown a marked decrease of the CD8+ T-cell population in the blood and we have described an infiltrate composed mainly of activated CD8+ T-cells in the liver lesions of most patients with AE. In this study, we assessed the serum level of soluble IL-2-receptor (sIL-2R) and CD8 (sCD8) in 37 patients (23 men, 14 women, mean age 59.5 yrs) with a histologically proven AE. The results, obtained using sandwich ELISA, were compared to those of healthy controls and correlated to parameters evaluating the severity of the disease. The mean serum levels of sIL-2R were significantly higher in AE patients than in controls. There was a significant correlation between sIL-2R levels and both the volume of parasitic lesions and a calculated index of severity of the disease. The mean serum levels of sCD8 did not differ significantly from the values obtained in controls. These results indicate that the infiltration of the liver by CD8+ T-lymphocytes is not associated with an increased release of sCD8 into the serum. The circulating levels of sIL-2R appear to reflect the extent as well as the severity of the disease. Immunostaining of the cells of the periparasitic granuloma suggests that the cell origin of the sIL-2R could be macrophages rather than T-lymphocytes.

Is debrisoquine hydroxylation modified during acute viral hepatitis?

Drug metabolism in the liver may be decreased during liver diseases. However, the extent of impairment of specific isozymes of cytochrome P450 is largely unknown. We have studied the debrisoquine hydroxylation capacity of 17 patients with acute viral hepatitis and 106 unrelated healthy subjects. Debrisoquine metabolic ratio was increased in extensive metabolizers (EM) with acute viral hepatitis as compared with healthy EMs (median metabolic ratio: 1.20 vs 0.84, P < 0.05). However, there was no difference in phenotype prevalence between patients and controls. Our results suggest that acute viral hepatitis only has a marginal effect on the activity of CYP2D6 and that substrates of this enzyme may be given in normal therapeutic doses to this category of patients.

Steroid sulfatase activities in normal and cirrhotic livers and plasma levels of estrone sulfate, estrone and estradiol-17 beta in men.

Estrone and dehydroepiandrosterone (DHEA) sulfatases were studied in livers of normal and cirrhotic men. Their Km were 3.2 microM and 1.2 microM respectively. The microsomal sulfatases were solubilized by Miranol H2M and ultrasound. After gel filtration, the soluble material gave a single peak of activity for both substrates with a molecular weight of approximately 330,000. In terms of pmol of product.min-1 per mg of fresh tissue, the mean (+/- SD) values of estrone and DHEA sulfatase activities were lower in cirrhotic livers [(n = 7) (4.09 +/- 2.90 and 0.38 +/- 0.20)] than in normal livers [(n = 13)(8.29 +/- 4.00 and 0.69 +/- 0.20)]. The differences were statistically significant : p less than 0.03 for estrone sulfatase and p less than 0.01 for DHEA sulfatase. In cirrhotic men, the mean level of plasma estrone is increased whereas that of estrone sulfate is decreased. The variations may be related to the decrease of serum albumin in cirrhotic subjects.

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

Interferon alpha therapy in haemophilic patients with chronic hepatitis C: a French multicentre pilot study of 58 patients.

BACKGROUND AND OBJECTIVES: Information about the long-term efficacy of interferon alpha (interferon-alpha) in haemophilic patients with chronic hepatitis not co-infected with the human immunodeficiency virus (HIV-1) is still limited. Previous studies seemed to indicate a low rate of response. The aim of this study was to evaluate the safety and long-term efficacy of interferon treatment in multi-transfused haemophiliacs. METHODS: Fifty-eight haemophiliacs were scheduled to receive 3 MU of interferon-alpha 2b three times a week for 12 months. The patients were followed up for at least 24 months post-treatment. Response was assessed by measurements of serum hepatitis C virus (HCV) RNA. RESULTS: Twenty-four patients (41.4%) dropped out. Except for seven patients, the symptoms that led to interrupting interferon treatment would probably not have resulted in the same decision in non-haemophilic patients. One patient developed an inhibitor to the deficient clotting factor without haemorrhagic consequences. In an intent to treat, the sustained virological response rate was 14%. However, when considering only the 34 patients who received the full treatment, HCV-RNA was cleared in eight patients (23%). CONCLUSIONS: This study suggests that multi-transfused haemophiliacs with chronic hepatitis not co-infected with HIV-1 respond to prolonged treatment with interferon-alpha in a similar proportion to that observed in non-haemophiliacs. There was a high rate of patients who did not complete the interferon-alpha treatment, and this seems to be characteristic of this patient population.

Acute fatty liver of pregnancy: CT evaluation. Case report.

CT scans of two patients with acute fatty liver of pregnancy were reviewed in conjunction with the clinical evolution of this uncommon and potentially fatal disorder. In each of the CT scans, liver density measurements were less than those of the spleen. While the findings are non-specific, in the proper clinical context they are highly suggestive and may be the sole method of diagnosis, as these patients often have coagulation problems which rule out liver biopsy. It is an important diagnosis, as the high maternal and fetal mortality rates appear to be considerably reduced by early foetal delivery.

Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis.

OBJECTIVE: To evaluate the polygenic regulated caffeine metabolism in a group of 67 patients with a documented primary biliary cirrhosis (PBC) classified according to the histologic stage proposed by Scheuer. METHODS: Over a 14-year period, drug liver metabolism, using caffeine as a probe drug, has been systematically carried out in addition to the usual clinical, histological and biochemical investigations performed in patients with PBC. The "Caffeine test" consisted of a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7-dimethylxanthine (17X), 1-3-dimethylxanthine (13X), 1-3-dimethylurate (13U), 3-7-dimethylxanthine (37X), 1-7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolite ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, AFMU/(AFMU+U+ 1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, patients with PBC presented a reduced metabolism of caffeine due to a decreased CYP1A2 activity, all the more important since the patients had an advanced histological stage. This picture was nearly identical to the observed picture in chronic liver diseases from various origins. PBC affected the various metabolic pathways of caffeine in a differential manner. CYP1A2 activity was decreased but XO and mainly CYP2A6 activities were increased as shown by the raised urinary ratio 17U/total metabolite elimination. In contrast to the described loss of bimodality of the NAT-2 index distribution in patients with alcoholic cirrhosis, we found a clear-cut, bimodal distribution in patients with PBC, without a high incidence of slow acetylator status. CONCLUSION: Metabolism of caffeine is strongly and differentially disturbed in patients with PBC and apparently not exactly in the same way as that in alcoholic cirrhosis which is more often taken as an index of chronic liver disease. This suggests the need for caution with medicines whose metabolism is under polygenic regulation. Because of the relationships between caffeine metabolism modifications and histological stages, the caffeine test might be used along with the usual tests to safely follow-up the evolution of the disease.

Relationship between the severity of alcoholic liver cirrhosis and the metabolism of caffeine in 226 patients.

OBJECTIVES: To evaluate the polygenic regulated caffeine metabolism in a group of 226 patients with liver alcoholic cirrhosis classified according to the Child score. METHODS: Over a 14-year period an hepatic function test, using caffeine as probe drug, has been systematically associated to the usual clinical and biochemical investigations performed in patients with liver alcoholic cirrhosis. "Caffeine test" consisted in a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7 dimethylxanthine (17X), 1-3 dimethylxanthine (13X), 1-3 dimethylurate (13U), 3-7 dimethylxanthine (37X), 1-7 dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolites ratios: (AFMU+1U+1X)/17U for CYPIA2, 17U/17X for CYP2A6, AFMU/(AFMU+ 1U+1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, whatever the Child score, caffeine metabolism was reduced by half in patients with alcoholic cirrhosis. The main cause was the decreased CYP1A2 activity. On the other hand, XO and CYP2A6 activities were increased and NAT-2 activity remained unchanged in slow acetylators (SA) and decreased in rapid acetylators (RA) Child B and C. Bimodality of NAT-2 distribution was unclear, but a right assignment of RA and SA phenotype in cirrhotic patients, confirmed by comparison with genotype, was obtained, using the antimode value of NAT-2 distribution used in healthy subjects. At last, there was an interindividual variability in caffeine metabolism as great as in the usual laboratory parameters. CONCLUSION: Metabolism of caffeine is decreased in patients with alcoholic liver cirrhosis. This decrease paralleled the modifications of the usual laboratory tests and does not bring additional information on the severity of the disease. But the equilibrium between the various metabolic pathways of caffeine is impaired. Beyond the changes of a specific enzymatic activity, this must be taken into account particularly for drugs whose metabolism is of the polygenic regulation type.

Caffeine metabolism before and after liver transplantation.

AIM: To study drug metabolism in patients before and after liver transplantation using caffeine as a probe drug. Forty-five patients undergoing liver transplantation for various liver diseases and who had well documented dossiers were selected for the study. Before the liver transplantation and 1 month, 1 year, and 6 years after liver transplantation, they were given 200 mg of caffeine by the oral route in the morning after voiding their bladder. Twenty-four-hour urine samples were collected and caffeine and metabolites were determined by HPLC: 1-methylurate (1U), 1-methylxanthine (1X), 1.7-dimethylurate (17U), 1.7-dimethylxanthine (17X), 7-methylxanthine (7X), 3-methylxanthine (3X), 1.3-dimethylurate (13U), 3.7-dimethylxanthine (37X), 1.3-dimethylxanthine (13X), 1.3.7-trimethylxanthine = caffeine (137X). Indices of enzyme activities were calculated from the following urinary elimination ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, 1U/1X for xanthine oxidase (XO), AFMU/(AFMU+1U+1X) for N-acetyltransferase (NAT-2). RESULTS: Compared with results obtained in a group of 70 healthy subjects, caffeine metabolism before liver transplantation was deeply depressed with a decreased elimination rate in the case of all metabolites and a decreased CYP1A2 activity. Caffeine metabolism began to return to the control values one month after transplantation. One year and 6 years after liver transplantation, quantitatively, the metabolism of caffeine was stable and not different from control, but with qualitative modifications. CYP1A2 activity was decreased with reduced urinary elimination rates of 1X and 17X. XO and CYP2A6 activities and 1U and 17U urinary elimination rates were increased. Immunosuppressive treatment was possibly responsible for the metabolic pathway changes. Almost the same modifications were observed in 9 patients after bone marrow transplantation who had been treated with the same immunosuppressive drugs, cyclosporine and azathioprine. During severe rejection phases in 6 of the liver transplant patients, caffeine metabolism was progressively decreased when the usual liver function tests showed moderate but uniform changes. CONCLUSION: Despite an apparent normal drug-metabolic function, immunosuppressive treatment induces stable variations in drugmetabolic pathways after liver transplantation which can be detected from the changes in caffeine metabolism.

Pulmonary embolism from a parasitic cardiac clot secondary to hepatic alveolar echinococcosis.

An exceptional form of hepatic alveolar echinococcosis with metastasis of the right atrium is reported. This cardiac location of the parasitosis was revealed by attacks of pulmonary embolism which produced secondary pulmonary lesions. This case suggests that pulmonary metastases of alveolar echinococcosis of the liver might be due to the migration of parasitic clots from the hepatic veins.

[Strategies of hepatitis C screening in general practice. Results of a two-center randomized trial]. / Stratégies de dépistage de l'hépatite virale C en Médecine générale. Résultats d'un essai randomisé bicentrique.

OBJECTIVES: To improve the detection of patients infected with hepatitis C virus. METHODS: A study was undertaken in the general medicine setting in two hepatitis C networks. General practitioners volunteered and received training on hepatitis C, then were randomly assigned to one of two screening strategies: group 1: general practitioners prescribed hepatitis C virus testing if the risk factors for HCV hepatitis C virus infection were identified during questioning of patients, group 2: general practitioners were helped in their screening approach by posters and leaflets on the risk factors of hepatitis C virus, available in the waiting room. RESULTS: A total of 184 general practitioners enrolled 90 from group 1 and 94 from group 2. During a 15-month-period, 617 serologies were prescribed, 323 by general practitioners in group 1 (in patients who were an average of 40 year-old) and 294 in group 2 (in patients who were an average of 44 year-old); 489 serologies (79.3%) were actually performed (261 and 228 respectively) and 25 (5.1%) tested positive (15 and 10 respectively). The number of prescribed, performed, and positive serologies did not differ from one group to the other. The motive for hepatitis C virus screening was similar in both groups and included a history of transfusion in 27% of cases, intravenous drug use in 6%, increased ALT or symptoms compatible with hepatitis in 13%, nosocomial exposure in 22%. Risk factors in the 25 patients who were hepatitis C virus positive were drug use (44%), history of transfusion before 1991 (16%), elevated ALT or symptoms (12%), others (28%). CONCLUSION: This study comparing screening strategies in general medicine, resulted in the diagnosis of hepatitis C virus infection in 5% of tested patients, regardless of the strategy. However, the fewer serologies prescribed by general practitioners (an average of 3 tests in a 15-month-period) suggests a low rate of identified risk factors in general practice, and emphasizes that other types of screening procedures should be implemented and evaluated.

[Treatment of human alveolar echinococcosis with flubendazole. Clinical, morphological and immunological study]. / Traitement de l'échinococcose alvéolaire humaine par le flubendazole. Etude clinique, morphologique et immunologique.

Flubendazole has been given at a daily dosage of 50 mg/kg for 16 months (extremes 10 and 24 months) to 10 patients with hepatic alveolar echinococcosis. Clinical, morphological and immunological evaluations have been performed every 2 months during the treatment, and in 6 patients after discontinuation of the drug for 24 months. Jaundice persisted or occurred in 7 patients; infectious complications were observed in 4 patients; portal hypertension appeared in 5 patients; metastatic spread was suspected in 2 patients. Subjective improvement and weight gain were reported by 6 patients during the first 4 months of treatment. Severe complications occurring during the period of FZ therapy or within 2 months after withdrawal of the drug led to surgery in 6 patients, and death occurred in 3 cases. These observations demonstrate the inefficacy of FZ in this series of 10 patients with alveolar echinococcosis, possibly related to the extremely poor bioavailability of FZ. Higher plasma concentrations obtained with mebendazole and albendazole could explain the better efficacy of these two drugs despite their similar chemical structures and experimental toxicity upon larval cestodes.

[Acute cytolytic hepatitis caused by coumarin. 2 cases]. / Hépatite aiguë cytolytique à la coumarine. Deux cas.

Coumarin is a drug which is extensively used to treat lymphedema. We report two cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year-old, were treated with 90 mg/d of coumarin for 5 months. Clinical features included jaundice, pruritus, and diarrhea. A marked increase in serum aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal, respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in both cases. Rechallenge in one case induced a relapse of symptoms and liver test abnormalities. Coumarin can induce acute cytolytic hepatitis.