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F Degos

Publications and source records attributed to F Degos.

At least 55 records · Page 3Linked to original sources
PubMed1995

Immunostaining for membrane attack complex of complement is related to cell necrosis in fulminant and acute hepatitis.

BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.

Acute Disease↗
PubMed1995

Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C.

BACKGROUND & AIMS: In patients with chronic hepatitis C treated with interferon alfa, sustained normalization of alanine aminotransferase was observed in about 20%, and no predictive factor of response could be clearly identified. The aims of this study were to assess the efficacy of an escalating dose of interferon and to determine the predictive factors of response. METHODS: Seventy-five patients were randomly assigned to two groups. Twenty-five patients received a dosage of 3 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, and 50 patients received a dose that was increased to 5 million units at 8 weeks in nonresponders and to 10 million units 8 weeks later in persistent nonresponders. Multivariate analysis was performed to determine the features associated with response. RESULTS: A sustained response was observed in 17% of the patients with constant dosage and in 19% of patients with an escalating dosage. Low pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype were found to be independent predictive factors of sustained response. CONCLUSIONS: In patients with chronic hepatitis C, an escalating dosage of interferon did not improve the overall rate of response. Low pretreatment serum hepatitis C virus RNA levels and genotype other than 1b were the only predictive factors of sustained response.

Adolescent↗
PubMed1995

CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C.

The pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 x 10(6) Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and 4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+ ratio of liver-derived lymphocytes was significantly higher (P < 0.01) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of gamma/delta T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio, the percentage of gamma/delta T lymphocytes or CD2+CD57+ cells according to genotype, the differences were not significant. These results suggest that the CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C, and that T lymphocytes may be involved in the pathogenesis of liver lesions in chronic hepatitis C.

Adult↗
PubMed1995

Adenine arabinoside 5'-monophosphate in patients with chronic hepatitis B: comparison of the efficacy in patients with high and low viral replication.

This study compared the response to adenine arabinoside 5'-monophosphate (ARA AMP) in 60 patients with chronic hepatitis B according to the pretreatment serum hepatitis B virus DNA concentration. The level of hepatitis B virus replication was defined as low (30 patients) or high (30 patients) when serum hepatitis B virus DNA concentration was below or above 100 pg/ml, respectively. Patients received a 28 day course of ARA AMP and a second course of ARA AMP was given six months later to patients with persistent hepatitis B virus replication. At the end of the first course of ARA AMP, 11 of the patients (37%) with low replication and one of the patients (3%) with high replication became negative for hepatitis B virus DNA (p = 0.0012); five of the patients (17%) with low replication and none of the patients with high replication had HBe seroconversion (p = 0.06). Two of these five patients lost HBsAg. Kinetics of serum hepatitis B virus DNA during treatment showed a considerable but transient antiviral effect of ARA AMP. Three of 32 retreated patients became negative for hepatitis B virus DNA and one patient had HBe seroconversion. In conclusion, ARA AMP exerts a considerable but transient antiviral effect on hepatitis B virus. Complete and sustained inhibition of hepatitis B virus replication was only obtained in the patients with low hepatitis B virus replication.

Adolescent↗
PubMed1995

Chronic cholestasis in patients after allogeneic bone marrow transplantation: several diseases are often associated.

From 1984 to 1991, 514 patients were treated by BMT in 1 center. 254 patients survived more than 3 months and, in 38 patients, 47 liver biopsies were performed for chronic liver dysfunction characterized by cholestasis. The aim of the present study was to evaluate the possible causes of liver disease at the time of biopsy. One clinician analyzed clinical data and was able to propose up to 3 diagnoses including GVHD, viral hepatitis, drug-related hepatitis, chronic veno-occlusive disease (VOD) or other. Two pathologists reviewed histologic sections and were also able to propose up to 3 diagnoses. Clinically, 1, 2 or 3 diagnoses were proposed in 30, 60 and 10% of cases, respectively. Pathologically, 1, 2 or 3 diagnoses were proposed in 13, 62 and 25%, respectively. Histologic changes of GVHD were present in 40 of 47 biopsies and concordance between the clinician and the pathologists on the presence of GVHD lesions was found in 77% of biopsies. Viral hepatitis was proposed 22 times by the clinician and 19 times by pathologists. Viral hepatitis, usually hepatitis C, was associated with GVHD in 16 cases. Diagnoses of chronic VOD and drug-related hepatitis were proposed less often. In summary, more than 1 diagnosis was suggested for many of the patients studied, GVHD being the most frequent. The simultaneous presence of GVHD, viral diseases, chronic VOD and drug-induced diseases could explain the high incidence of cholestasis in the long-term post-BMT.

Adolescent↗
PubMed1994

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B.

T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388 pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher (P < 0.05) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the gamma/delta receptor and that of CD2+/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication, CD4+CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P < 0.001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B, the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytotoxic T cell activity in patients with HBV-related chronic hepatitis.

Adult↗
PubMed1994

Epidemiology of hepatitis C virus in Europe.

Epidemiology of Hepatitis C virus (HCV) infection in Europe is changing very rapidly since the main source of contamination was blood transfusion and the use of surrogate markers allowed to diminish dramatically the number of patients contaminated through HCV post transfusion hepatitis. The recent description of several genotypes with different distributions over Europe and different pathogenicity will allow to explain various evolutive aspects of the disease. At present, groups at risk are drug addicts (70%), hemophiliacs (contaminated with blood products before 1985), hemodialysis patients (20%) and patients with cirrhosis with or without hepatocellular carcinoma. The detection of HCV markers prior to blood transfusion allowed to detect asymptomatic carriers of HCV, some of them with latent chronic hepatitis which can be predicted by the detection of HCV RNA in the serum. Vertical and sexual transmission are rare but possible events observed with certainty in patients co-infected with HIV and controversial in other situations.

Carrier State↗
PubMed1993

[Cytokines and hepatitis].

Interferon is presently the treatment of chronic liver infection with hepatitis B and C viruses. Major advances have been made in the field of hepatitis B virus with interferon, which is able to clear viral replication in 30 to 40% of the cases. Interferon is also efficient in the treatment of hepatitis C chronic infections, normalizing transaminase activity in 60 to 70% of the patients, but a relapse is observed after interruption of treatment, and a sustained remission is obtained in only 20% of the cases. These results demonstrate the need for further clinical research to elucidate the precise indications of this treatment.

Cell Division↗
PubMed1993

Assessment of screening tests for transfusion-associated non-A non-B hepatitis.

Non-A non-B hepatitis is the most common serious sequela of blood transfusion, and its screening has become an essential goal of blood transfusion centers. Before 1989, two surrogate screening tests (for alanine aminotransferase and for antibody to hepatitis B core antigen) were used; in 1989, a direct test for the antibody to hepatitis C virus (the main agent of this hepatitis) was developed. The French National Agency for the Development of Medical Evaluation undertook an investigation to determine the optimal prevention strategy for posttransfusion non-A and non-B hepatitis (PTH). A detailed literature review was performed, complemented by expert group opinion. The performance of each test was derived indirectly by calculating the number of cases of PTH averted by each test. Hepatitis C virus testing is probably the most promising strategy, but different policies can be developed given the uncertainties of scientific data. Cost considerations should be taken into account in identifying the best screening strategy.

Alanine Transaminase↗
PubMed1992

Failure of acyclovir to enhance the antiviral effect of alpha lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B. A multi-centre randomized controlled trial.

Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and six controls (14%) (difference: 11%, 95% CI-5-28%). A partial response (HBeAg less than 50% of initial level) was found significantly more often for treated patients (n = 13, 30%) than for controls (n = 2, 5%) (difference: 25%, 95% CI 10-40%). During acyclovir-interferon combination therapy the decrease in HBeAg level was similar to that achieved during therapy with interferon alone. We conclude that acyclovir does not enhance the effect of interferon on serum HBeAg levels. Since HBeAg levels continue to decline during interferon treatment and rebound thereafter to pretreatment levels, prolongation of therapy may yield a higher response rate.

Acyclovir↗
PubMed1992

Recombinant interferon-alpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus. Comité des Anti-Viraux.

To assess the response to and tolerance of recombinant interferon-alpha administration in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection, 12 patients with chronic hepatitis C and HIV infection were given interferon-alpha, 1, 3, or 5 million units thrice weekly, for 4 or 6 months. Four patients had a complete response (normal serum alanine aminotransferase activity [ALT]), 3 had a near-complete response (serum ALT less than one-and-one-half times the upper limit of normal), and 5 had no response at the end of administration. Histologic examination of liver showed an improvement in 1 patient with complete response and no improvement in another patient with no response. In patients with chronic hepatitis C with HIV infection, the response to and tolerance of recombinant interferon-alpha were not different from those usually observed in patients with chronic hepatitis C infection without HIV infection.

Adult↗