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Biomedical subjects

P Marcellin

Publications and source records attributed to P Marcellin.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Natural history of dysthyroidism during interferon treatment of chronic hepatitis C].

Thyroid dysfunction developed in 35 patients among a series of 300 (190 men and 110 women) treated with alpha-interferon (35/300 = 12%. No relationship was observed between the type of alpha-interferon, the dose, or hepatic response, but there were more women (24/35). Antithyroid antibody levels were frequently elevated before treatment (8/35, 23%). Hypothyroidism developed in 27 patients, 7 with clinical hypothyroidism, 10 with moderate hypothyroidism and 5 with elevated TSH only. Patients with severe symptoms and highly elevated thyroid antibodies were more prone to develop sustained or irreversible hypothyroidism (10 patients). Twelve patients recovered a normal thyroid function within a few months, but antibody levels fell more slowly. Primary hyperthyroidism of variable severity appeared in 13 patients. In 8 patients, normal thyroid function was recovered within a few weeks but thyroid antibodies remained high for at least one year. In 5 others spontaneous hypothyroidism occurred within a few weeks ("biphasic" hypothyroidism). Direct toxicity appears to be less probable than an autoimmune mechanism; elevated antithyroid antibodies were observed in only 20 patients (57%). In clinical practice, TSH levels should be regularly monitored during and after alpha-interferon therapy.

Adult↗
PubMed1995

Hepatitis C virus genotypes in French blood donors.

The prevalence of different hepatitis C virus (HCV) genotypes in HCV infected individuals and the relation between the HCV genotypes and the source of the infection are controversial. The aim of this study was to determine the HCV genotypes in French blood donors. Fifty-one anti-HCV positive blood donors were studied with detectable serum HCV RNA by nested polymerase chain reaction (PCR) using primers derived from the 5' non-coding region. For genotyping HCV, we used a method based on analysis of the restriction fragment length polymorphisms (RFLP) after amplification by PCR of the HCV non-structural 5 (NS5) genome domain. Using this technique, the genotypes of 39 of the 51 blood donors (76%) were determined. Three previously described genotypes were found: 19 blood donors were infected by HCV genotype I (37%), 14 were infected by HCV genotype II (27%), 3 were infected by HCV genotype III (6%), and 3 were coinfected by two genotypes (6%). All three blood donors infected with two different genotypes were intravenous drug abusers. A past history of intravenous drug abuse was more frequent in blood donors with HCV genotype I. However, there was no difference in alanine transaminase (ALT) levels, histological lesions, and RIBA-2 patterns in blood donors infected with either HCV genotype I or HCV genotype II. These findings indicate that most HCV genotypes isolated from French blood donors belong to HCV genotype I and HCV genotype II, and that risk factors for HCV infection may differ for different genotypes of HCV.

Adult↗
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

Hepatitis B virus precore mutations and HBeAg negative reactivation of chronic hepatitis B after interferon therapy.

The objective of this study was to look for HBV precore mutations in three patients with chronic active hepatitis B who developed HBV-DNA-positive/HBeAg-negative reactivation after HBe seroconversion induced by interferon therapy. Direct sequencing of polymerase chain reaction products was performed on serum collected before and after HBe seroconversion. In two patients precore sequence showed only wild-type HBV before and after interferon therapy. In one patient, precore sequence showed only wild-type HBV before interferon therapy and a mixed infection by wild-type HBV and precore mutant viruses (1858 and 1896 nucleotide mutations) after treatment. The presence of HBeAg/anti-HBe immune complexes was found after HBe seroconversion in all cases. Our results suggest that: 1) precore mutations are not always found in patients with chronic hepatitis B who develop HBV DNA-positive/HBeAg-negative reactivation; and 2) HBeAg negativity, despite the presence of wild-type HBV, might be due to HBeAg/anti-HBe immune complexes. We speculate that the production of these immune complexes may be favored by interferon therapy.

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

Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C.

The aim of the study was to determine the respective influence of pretreatment serum hepatitis C virus (HCV) RNA levels and HCV genotype on the response to interferon (IFN) alfa in patients with chronic hepatitis C. We retrospectively studied 141 patients with chronic hepatitis C included in two consecutive controlled trials of IFN alfa. A sustained response was observed in 28, a response followed by relapse in 43, and no response in 70 patients. Pretreatment serum HCV RNA quantitation with the branched DNA (bDNA) assay and HCV genotyping with reverse hybridization assay (LiPA) were performed in all patients. Seventy-four percent of the patients had detectable serum HCV RNA (43%, 77% and 84%) in the three groups of patients with sustained response, relapse, and no response, respectively (P = .005). Mean serum HCV RNA level were 1.4 +/- 6 x 10(6), 4.8 +/- 6 x 10(6), and 3.9 +/- 5 x 10(6) genomes/mL in patients with sustained response, response and relapse, and no response, respectively (P < .01). Genotype 1b was found in 7%, 47%, and 46% of the patients in the three response groups, respectively. By univariate analysis, age, source, and duration of HCV infection, serum HCV RNA levels, and HCV genotypes were significantly different in the three response groups. By multivariate analysis, the only independent factors associated with sustained response were low serum HCV RNA levels and HCV genotype other than 1b. Pretreatment serum HCV RNA levels and HCV genotype are the main and independent factors associated with sustained response to IFN therapy.

Adult↗
PubMed1995

Low frequency of precore hepatitis B virus mutants in anti-hepatitis B e-positive reactivation after loss of hepatitis B e antigen in patients with chronic hepatitis B.

The objective of this study was to evaluate the role of hepatitis B virus (HBV) precore mutations in patients with anti-HBe-positive chronic hepatitis B with or without previous known HBe antigen (HBeAg) viremic phase, and to assess the potential implication of precore mutants in HBeAg-negative reactivation after loss of HBeAg. Nineteen patients were studied: 7 had a previous HBeAg-positive phase and had spontaneous or therapeutically induced loss of HBeAg (group A); 12 had no previous HBeAg-positive phase (group B). Direct sequencing of PCR products was performed on serum collected during the anti-HBe-positive phase in the two groups. In group A, precore sequencing showed that 5 patients were infected by wild-type virus, 1 patient was infected with a precore mutant, and 1 patient was found to be infected by a mixture of wild-type and precore mutant viruses. In group B, precore sequencing showed that only 1 patient was infected with wild-type virus and that 11 were infected with precore mutants. In a few patients, the presence of HBeAg within immune complexes may explain HBeAg negativity. In conclusion, our results show that, in patients with anti-HBe-positive chronic hepatitis B: (1) precore mutations creating a stop codon are more frequently found in those without known previous HBeAg positivity; (2) after loss of HBeAg, the patients who have anti-HBe-positive reactivation are infected by wild-type virus, which suggests that reactivation is not related to precore mutations; (3) HBeAg negativity may be caused by immune complexes formation.

Adult↗
PubMed1995

[Natural history of hepatitis C virus infection].

Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute hepatitis. HCV infection becomes chronic in about 80% of cases. Chronic HCV infection is asymptomatic with persistent viremia and normal liver tests in a minority of the subjects. Chronic HCV infection is associated with chronic hepatitis with increased serum transaminases levels in the majority of the subjects. Among the patients with chronic hepatitis, the majority have minimal lesions; about 20% have a more severe disease and will develop after 5 to 20 years cirrhosis. In patients with cirrhosis, the incidence of hepatocellular carcinoma is high (around 5% per year). The factors influencing the evolution of HCV infection are not know. Alcohol is certainly an important factor. Virus related factors, such as genotype and level of replication, might also be important factors.

Carcinoma, Hepatocellular↗
PubMed1994

Expression of cytokine-dependent immune adhesion molecules by hepatocytes and bile duct cells in chronic hepatitis C.

BACKGROUND/AIMS: The pathogenesis of liver cell injury in chronic hepatitis C is poorly understood. To test whether immune-mediated mechanisms might be involved in the pathogenesis of liver cell injury during infection by hepatitis C virus, the expression of cytokine-dependent immune molecules by hepatocytes and bile duct cells during chronic hepatitis C was studied. METHODS: In 35 patients, expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM) 1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry and scored by a semiquantitative grading system. Statistical analysis was performed using Spearman's test and t test. RESULTS: Class I HLA antigens were induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3 were detected on hepatocytes in piecemeal necrosis and intralobular clusters. Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases. Expression levels of immune molecules on hepatocytes correlated with aminotransferase activity (P < 0.035), histological activity (P < 0.001), and score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM-1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P < 0.015). CONCLUSIONS: These results suggest the involvement of immune-mediated mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.

Adult↗
PubMed1994

Treatment of chronic viral hepatitis.

Recent advances have been made in the treatment of chronic viral hepatitis, mainly with recombinant interferon (IFN) alpha. However, the present treatment of chronic viral hepatitis is not entirely satisfactory because the efficacy is inconstant and/or incomplete. In chronic hepatitis B IFN-alpha induces a sustained interruption of hepatitis B virus (HBV) replication, with a HBeAg to anti-HBe seroconversion in about 30% of patients. Patients most likely to respond are those with no immunosuppression, HBV infection acquired during adulthood or active liver disease with low HBV replication. Responders usually show a significant decrease in serum HBV DNA levels during the first 2 months of therapy, followed by a significant increase in the level of aminotransferases. New nucleoside analogues might be useful in combination with IFN-alpha in the treatment of those who do not respond to IFN therapy. In chronic hepatitis B-D, the rate of sustained response to IFN-alpha therapy is low. To be effective, IFN-alpha must be used at a high dosage (9-10 mega units) with a long duration (1 year). In chronic hepatitis C, IFN-alpha at a dosage of 3 mega units over 6 months, induces a sustained response in about 20% of patients. A higher dosage of IFN (5-10 mega units) and a longer duration of treatment increases the rate of sustained response but is associated with poor tolerance. Non-responders to a first course of IFN do not respond to a second course of treatment. In patients who respond but relapse after treatment, the rate of sustained response after a second course of IFN needs to be assessed. Ribavirin, which has a significant antiviral effect on hepatitis C virus, might be useful in combination with IFN-alpha. At the dosage (3-6 mega units) usually used, IFN-alpha is relatively well tolerated. In about 10% of the patients therapy is interrupted, mainly because of severe fatigue, thyroid dysfunction or depression.

Controlled Clinical Trials as Topic↗