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Biomedical subjects

F Lunel

Publications and source records attributed to F Lunel.

At least 73 records · Page 4Linked to original sources

[Hepatitis C virus. Virological diagnosis].

Hepatitis C virus (HCV) has been discovered in 1989 and is probably the most common cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a single-stranded, positive-sense RNA virus, 9.4 kilobases in length. The genetic organisation and the properties of viral proteins have been characterized. At least 50 HCV genotypes or subtypes have been identified. Genotypes 1, 2 and 3 are the most commonly observed in patients from Europe and USA. Genotype 1 is more resistant to interferon treatment. The hypervariability of HCV is responsible, within a single patient, of the existence of a spectrum of very closely-related genomes reffered as quasispecies that may be a mechanism of escape from the immune response and may explain chronicity. Virological diagnosis of HCV infection is based on the detection of anti-HCV antibodies by ELISA. In some cases (acute hepatitis, problems in the interpretation of ELISA tests, or in immunosuppressed patients), it is necessary to search for HCV RNA using genomic amplification or amplification of hybridization. These technics can also be useful to predict the response to interferon, as it has been demonstrated that patients with low viremia are better responders than others. HCV RNA detection or quantification could also be useful to follow the efficiency of anti-viral drugs.

DNA Probes↗

[Extrahepatic manifestations related to hepatitis C virus].

The hepatitis C virus infects mononuclear cells and, like other viruses, can be responsible for immune disorders. The immune abnormalities described in the course of hepatitis C consist of nonspecific immunological disorders (cryoglobulinaemia, autoimmune disorders, generally associated with the presence of organ-specific or nonspecific autoantibodies). The association between mixed cryoglobulinaemia and hepatitis C has been clearly established, as 50% of patients with essential cryoglobulinaemia suffer from hepatitis C and 50% of patients with hepatitis C suffer from cryoglobulinaemia. The relationships between hepatitis C and other autoimmune disorders is less clear. The association between hepatitis C and anti-smooth muscle and antinuclear antibodies has been emphasized. However, the frequency of these autoantibodies in hepatitis C does not appear to be significantly different from than observed in other forms of viral hepatitis, especially hepatitis B. However, patients with hepatitis C have a higher incidence of anti-LKM1 antibodies than patients with other forms of viral or alcoholic liver disease. A high prevalence of hepatitis C viral infection has also been reported in Sjögren's syndrome, lichen planus and thyroid disorders. However, the relationship between viral infection and these immune disorders has not been demonstrated by large-scale epidemiological surveys or by basic virological studies. The development or exacerbation of immune disorders in patients treated by interferon has also been clearly demonstrated, which means that an autoimmune assessment, especially looking for anti-tissue and anti-thyroid antibodies, should be performed before prescribing interferon.

Cryoglobulinemia↗

Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.

BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study. METHODS: The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. RESULTS: The prevalence of mixed cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. CONCLUSIONS: These findings suggest that HCV is a major cause of cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.

Adult↗

Indeterminate third-generation recombinant immunoblot assay in hepatitis C virus infection. Group d'Etudes Moléculaires des Hépatites (GEMHEP).

Third-generation recombinant immunoblot assay is widely used for the validation of the serological diagnosis of hepatitis C virus infection. To determine whether indeterminate recombinant immunoblot assay 3.0 patterns may be associated with viral replication and liver disease, 89 indeterminate patterns were studied (67 c22n 14 c33c, 5 c100p and 3 NS5); 35 (39%) had immunosuppression. Serum alanine aminotransferase activity was increased in 49 (55%); HCV RNA was evidenced through polymerase chain reaction in 52 (58%). The observation of indeterminate recombinant immunoblot assay 3.0 justifies investigation of liver disease and search for HCV RNA, since a large proportion of individuals with such patterns are hepatitis C virus-infected.

Adolescent↗

[Prevalence and significance of non-specific anti-organelle antibodies of the liver in chronic viral hepatitis C].

OBJECTIVES: The aim of this study was to evaluate the prevalence and the clinical signification of non organ specific autoantibodies in chronic hepatitis C. METHODS: We studied retrospectively 158 consecutive patients (97 with chronic hepatitis C, 24 with chronic hepatitis B, 67 with alcoholic cirrhosis) and 100 blood-donors. RESULTS: The prevalence of anti-nuclear and anti-smooth muscle antibodies was lower in blood donors than in patients (P < 0.001), but was comparable among the 3 groups of patients. The anti-liver-kidney microsome type 1 antibodies were detected only in patients with chronic hepatitis C (6%). The serum gammaglobulin level was significantly higher in patients with hepatitis C and anti-nuclear antibody titers > or = 1/50. The anti-smooth muscle antibodies detected in patients with hepatitis C had no anti-actin specificity. The response to interferon was not related to the detection of non organ specific autoantibodies before treatment. CONCLUSION: Anti-nuclear or anti-smooth muscle antibodies are not characteristic of hepatitis C virus infection.

Adult↗

[Cholestatic viral hepatitis A in adults. Clinical, biological and histopathological study of 9 cases].

OBJECTIVES: We report here 9 cases of acute viral hepatitis A leading to hospitalization between June 1989 and October 1992. The main feature was a marked and protracted cholestasis. RESULTS: Jaundice lasted an average of 77 +/- 39 days (range: 30-120) and total serum bilirubin concentrations were 265 +/- 184 mumol/L (range: 51-560). IgM anti-HAV was present in the serum for 6.3 +/- 5.5 months (median: 4, range: 2-19). Histopathological examination of the liver was performed in 6 patients and most showed intralobular cholestasis and portal tract inflammation associated with dystrophy and paucity of bile ducts. Acute renal failure was noted in one patient. In three patients, whose pruritus was not relieved by cholestyramine, plasma exchange was an effective therapy. CONCLUSION: These case reports confirm the severity of viral hepatitis A in adults and emphasize the importance of vaccination.

Acute Kidney Injury↗

Post-transfusional anti-HCV-negative, non-A, non-B hepatitis. (I) a prospective clinical and epidemiological survey.

Despite the identification of hepatitis C virus (HCV) and the detection of anti-HCV antibodies in the serum of infected individuals, a sizeable proportion of patients who develop transfusion-associated acute non-A, non-B hepatitis following surgery do not develop anti-HCV antibodies. The cause of this disease remains unknown. To assess the role of homologous blood transfusion in anti-HCV-positive and -negative, non-A, non-B hepatitis following surgery, patients receiving homologous blood, autologous blood alone, or no transfusions were prospectively studied. Consumption of potentially hepatotoxic drugs was also quantified. Anti-HCV antibodies were tested retrospectively when commercial assays became available. Of the 181 patients who received homologous blood which tested negative for surrogate markers of infectivity, 19 (10.5%) developed non-A, non-B hepatitis, associated with anti-HCV seroconversion in three cases. Of the 90 autologous blood recipients, non-A, non-B hepatitis developed in one (1.1%), who did not seroconvert to anti-HCV. Of the 64 untransfused patients, non-A, non-B hepatitis developed in one (1.6%), who was anti-HCV-positive before surgery. Logistic regression analysis showed that the occurrence of non-A, non-B hepatitis was associated with homologous blood transfusion, but not with the consumption of potentially hepatotoxic drugs. The 16 homologous-blood recipients who developed anti-HCV-negative, non-A, non-B hepatitis had received blood from 70 donors, none of whom had detectable anti-HCV antibodies but six of whom had minimal elevations of serum aminotransferase activity. Anti-HCV-negative, non-A, non-B hepatitis is mainly transfusion-transmitted in the surgical setting. Known hepatotropic agents may be involved despite the absence of usual serum markers, but our results are also consistent with the involvement of an unidentified non-A, non-B, non-C agent.

Adult↗

Post-transfusional anti-HCV-negative non-A non-B hepatitis (II) serological and polymerase chain reaction analysis for hepatitis C and hepatitis B viruses.

Hepatitis C virus (HCV) is a major etilogical agent of post-transfusional and sporadic acute and chronic hepatitis in various geographical areas. However, anti-HCV seroconversion was uncommon in a recent study of patients with post-transfusional hepatitis in Paris, France (N. Asar et al., companion paper). The aim of the present study was to detect viral markers, in particular HCV RNA and hepatitis B virus (HBV) DNA, in these patients. A combination of second-generation assays for anti-HCV antibodies and the polymerase chain reaction were used to identify HCV RNA and HBV DNA sequences in serum samples collected before and after transfusion from patients who developed non-A, non-B hepatitis. Eighteen cases of acute, post-transfusional, non-A, non-B hepatitis were identified in the prospective clinical survey. Only three of these 18 subjects developed anti-HCV antibodies in second-generation tests. HCV RNA was identified in the serum of these three subjects but in none of the others. Two patients who were anti-HCV-negative had polymerase chain reaction evidence of HBV DNA. Known viral markers were not identified in 13 of the 18 patients with acute post-transfusional non-A, non-B hepatitis. These results raise the issue of HCV strains or 'non-A, non-B, non-C' viruses not identified by current HCV and HBV markers and implicated in post-transfusional hepatitis in France.

Base Sequence↗

Non-organ specific autoantibodies associated with chronic C virus hepatitis.

Recently antibodies to hepatitis C virus were detected in sera of chronic active hepatitis patients, with anti-smooth muscle autoantibodies or with anti-liver/kidney microsomal type 1 autoantibodies. As the latter were used to differentiate autoimmune chronic active hepatitis from chronic non-A, non-B virus hepatitis, it was mainly important to discover if autoantibodies were associated with chronic hepatitis C virus infection. The sera of 272 chronic hepatitis C patients were screened by indirect immunofluorescence for non-organ specific autoantibodies. Antinuclear antibodies and anti-smooth muscle autoantibodies were more frequent in chronic hepatitis C patients than in blood donors (n = 100). Anti-liver/kidney microsomal type 1 autoantibodies were not detected in the sera of the blood donors, in the 74 hepatitis B patients or in the 30 alcoholic hepatitis or cirrhotic patients' sera tested as controls. They were detected in 14 chronic hepatitis C patients. These antibodies were compared in immunodiffusion to anti-liver/kidney microsomal type 1 autoantibodies sera obtained from type-2 autoimmune chronic active hepatitis patients and an identity reaction was observed. Chronic hepatitis C patients without or with anti-liver/kidney microsomal type 1 autoantibodies, did not differ in age, sex ratio, transaminases and gammaglobulin level, risk factors for hepatitis C virus infection, association with other autoimmune diseases. These patients differed significantly from type-2 autoimmune chronic active hepatitis patients. We conclude that: (i) in some chronic hepatitis C patients the pattern and the titer of autoantibodies may create confusion with an autoimmune chronic active hepatitis; (ii) There is no serological evidence for a hepatitis C virus infection in true type-2 autoimmune chronic active hepatitis.

Adolescent↗

[Western blotting analysis of cryoglobulins associated with chronic hepatitis C].

In a prospective study, a monoclonal component was found in 29/89 (33%) of mixed cryoglobulinemia (MC) associated with hepatitis C virus (HCV) infection, with a IgM in 87% of cases and a Kappa/Lambda ratio at 1.8. HCV RNA anti-HCV antibodies were demonstrated in both MC with and without monoclonal component.

Blotting, Western↗

Liver/kidney microsome antibody type 1 and hepatitis C virus infection.

Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney microsome antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5' noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assay-positive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 +/- 11 vs. 50 +/- 11 years) and had higher gamma-globulin levels and liver/kidney microsome antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man.

Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.

Adolescent↗