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P Marcellin

Publications and source records attributed to P Marcellin.

At least 19 recordsLinked to original sources
PubMed1997

Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy.

BACKGROUND: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-alpha therapy. The long-term benefit of interferon-alpha with regard to hepatic viral clearance and histologic improvement remains unknown. OBJECTIVE: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-alpha therapy. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-alpha therapy, and were followed for at least 12-months. MEASUREMENTS: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment. RESULTS: The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested. CONCLUSIONS: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

Alanine Transaminase↗
PubMed1997

Influence of hepatitis G virus infection on the severity of liver disease and response to interferon-alpha in patients with chronic hepatitis C.

BACKGROUND: Dual infection with hepatitis G virus (HGV) and hepatitis C virus (HCV) is common. The effect of HGV infection on chronic hepatitis C is not well known. OBJECTIVE: To assess the prevalence of HGV infection; the effect of HGV infection on the clinical, virologic and histologic features of patients with chronic hepatitis C treated with interferon-alpha; and the influence of HGV infection on response to interferon-alpha therapy. DESIGN: Retrospective study. SETTING: A university hospital in France. PATIENTS: 228 patients with chronic hepatitis C treated with interferon-alpha (3 million U or 5 million U subcutaneously 3 times a week for 3, 6, or 12 months). MEASUREMENTS: Before initiation of treatment, serum HGV RNA and serum HCV RNA were detected with branched-DNA assays and HCV genotype was determined with a line probe assay. Serum HGV RNA and serum HCV RNA were detected by polymerase chain reaction at the end of treatment and 6 months after treatment. RESULTS: Infection with HGV was detected in 21% of patients and 32% of intravenous drug users. The median serum HGV RNA level was 33 x 10(6) genome equivalents/mL. Infection with HGV was more frequently found in men with a history of intravenous drug use and was associated with HCV genotype 3a (P = 0.02) independent of the source of infection. Serum HCV RNA levels, liver histologic findings, and response to interferon-alpha therapy did not differ between patients with and those without HGV infection. The loss of serum HGV RNA was not correlated with the biochemical response contrarily to the loss of serum HCV RNA. CONCLUSIONS: Infection with HGV occurred frequently in this sample of patients with chronic hepatitis C, especially in patients infected with HCV genotype 3a. The level of HGV viremia was high relative to the level of HCV viremia. Infection with HGV did not influence the severity of liver disease or response to interferon-alpha therapy.

Adult↗
PubMed1997

Therapy of hepatitis C: patients with normal aminotransferase levels.

An important group of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels despite having hepatitis C virus (HCV) RNA detectable in serum. These patients are typically identified after donating blood and being found to be positive for antibody to HCV (anti-HCV). A strict definition of this patient population is needed, which should include presence of anti-HCV, HCV RNA detectable by polymerase chain reaction (PCR), and persistently normal ALT levels. These patients are usually asymptomatic, but almost all have histological evidence of chronic hepatitis on liver biopsy. The liver histological lesions are generally mild, and cirrhosis is rare. The long-term outcome of this group of patients with chronic HCV infection is not known, but the prognosis is probably good. In small, uncontrolled trials of alpha interferon in this group of patients, end-of-treatment virological responses occurred in approximately 50% and sustained responses 6 to 12 months afterwards in 20%. These rates of response are not very different from those reported in patients with abnormal ALT levels. Importantly, in most studies, serum ALT levels became abnormal during therapy in approximately half of patients, and levels remained abnormal in a proportion after therapy. These findings suggest that alpha interferon therapy is not usually beneficial and may be harmful in patients with chronic hepatitis C who have normal ALT levels, perhaps as a result of the immunomodulatory actions of alpha interferon that may alter the balance of host immune reactions and viral replication, which seem to be responsible for the liver injury in chronic hepatitis C.

Alanine Transaminase↗
PubMed1997

Acute hepatitis induced by alpha-interferon, associated with viral clearance, in chronic hepatitis C.

We describe the cases of two patients with chronic hepatitis C who developed acute hepatitis with marked amino-transferase elevations and jaundice 3 and 5 months after initiation of interferon treatment. Hepatitis resolved rapidly after cessation of interferon. No autoantibodies were detected. Hepatitis was followed by viral clearance, demonstrated by clearance of hepatitis C viraemia. We propose that hepatitis may be due to an immune lysis of hepatocytes and suggest that this immune response may contribute to viral clearance.

Acute Disease↗
PubMed1997

Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg.

BACKGROUND/AIMS: The persistence of serum and liver hepatitis B virus (HBV) sequences in patients with chronic hepatitis B after loss of HBsAg has already been described. We have attempted to elucidate the significance of these HBV sequences after loss of HBsAg. METHODS: Fifteen patients were studied. We looked for serum and liver HBV DNA, using polymerase chain reaction (PCR) with different sets of primers and in situ hybridization. The sedimentation velocity of serum HBV DNA was measured on a gradient of sucrose in two patients. RESULTS: Serum HBV DNA was detected by PCR in four of the 14 patients tested at 0 months after loss of HBsAg, two patients remained HBV DNA positive until 12 months, and none was positive at 24 months. The sedimentation velocity of serum HBV DNA in sucrose was relatively similar to that of a chronic HBV carrier with active viral replication. Liver HBV DNA was demonstrated by PCR in all 15 patients and by in situ hybridization in six patients. CONCLUSIONS: Our results show that: 1) HBV DNA may persist in the serum in a minority of patients and may be associated with circulating viral particles; 2) HBV DNA persists in the liver in all patients and its extrachromosomal localization was shown by in situ hybridization technique in some cases. These results suggest the persistence of low-level HBV replication after loss of HBsAg.

Adult↗
PubMed1997

Subfulminant syncytial giant cell hepatitis: recurrence after liver transplantation treated with ribavirin.

We report the case of an adult patient affected by acute syncytial giant cell hepatitis which had a subfulminant course leading to liver transplantation. Syncytial giant cell hepatitis recurred after transplantation and was efficiently treated with ribavirin. In this patient, the recurrence of the disease, the presence of filamentous strands on electron microscopy during both bouts of hepatitis and the efficacy of ribavirin on post-transplantation hepatitis suggest that the disease was caused by an original virus. This observation also suggests that early administration of ribavirin in patients affected by acute syncytia; giant cell hepatitis of unknown origin could avoid liver transplantation.

Acute Disease↗
PubMed1997

Early negative tests for serum HCV RNA as a predictor of sustained response to interferon therapy in patients with chronic hepatitis C.

In patients with chronic hepatitis C, the main predictors, before treatment, of sustained response to interferon therapy are serum hepatitis C virus (HCV) RNA level and HCV genotype. During treatment, early response with normalization of serum alanine aminotransferase (ALT) and negative tests for serum HCV RNA are predictive of a sustained response. In the absence of early response observed within the first three months of therapy, the chance of sustained response is very low and interruption of interferon therapy may be considered.

Alanine Transaminase↗
PubMed1997

Prolonged interferon-alpha therapy of hepatitis B virus-related decompensated cirrhosis.

Interferon alpha therapy of hepatitis B virus-related decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3-48 months) low-dose (3 million units) IFN-alpha therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5-7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-alpha therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.

Adult↗
PubMed1997

GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum.

PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.

Flaviviridae↗
PubMed1997

Incidence of dysthyroidism during interferon therapy in chronic hepatitis C.

Seventy-nine patients (40 males, 39 females) were enrolled in a prospective study of lymphoblastoid interferon-alpha (IFN), 3-5 MU three times weekly. They were randomly assigned to receive either 12 months of IFN therapy, or to 6 months of observation followed by 6 months of IFN therapy. The thyroid functional and immunological status was checked every other month during and after treatment. Before treatment, antithyroid antibodies were found in 6 patients (7.5%). Two were hypothyroid and were excluded from the study before starting IFN therapy. Seventy-seven patients received IFN therapy. Of these, thyroid abnormalities appeared in 6 (7.5%). Hyperthyroidism was observed in 3 patients. Two recovered within a few months, but 1 developed subsequent hypothyroidism. Hypothyroidism was observed in 2 patients. TSH blood values were persistently abnormal, but thyroid antibody levels remained increased and fluctuating. Thyroid function usually recovered within a few months; but 2 patients required hormonal therapy and 1 was treated with carbimazole. In 1 patient, a small thyroid papillary carcinoma was observed, but no evidence of relationship with the liver disease or with IFN therapy was found. In a patient with chronic hepatitis C, systematic thyroid assessment should be performed before initiating IFN therapy, including clinical examination, and measurement of TSH and anti-thyroperoxidase antibodies (TPO Ab). During treatment, a TSH assay every other month appears to be necessary and sufficient.

Adult↗
PubMed1996

Interferon-alpha therapy for chronic hepatitis C in special patient populations.

Interferon-alpha therapy for chronic hepatitis C in special patient populations raises a number of issues. Patients with hemophilia, kidney disease requiring hemodialysis, mixed cryoglobulinemia, HIV infection, and those receiving an allograft share some characteristics that complicate the treatment of hepatitis C virus infections. These patients generally have some degree of immune deficiency, higher levels of hepatitis C virus replication, and are infected with genotypes 1a or 1b. Each of these characteristics is often associated with a poor response to interferon therapy. Clinical research in this area also has been limited. Current data and clinical experience demonstrate that interferon-alpha therapy should be considered in patients with hemophilia who have concurrent hepatitis C viral infection. Other hepatitis C virus-infected patient populations in which interferon-alpha therapy may be beneficial include those undergoing hemodialysis, mixed cryoglobulinemia, or HIV infection. Further, the high incidence of relapse following treatment cessation in these patients warrants prolonged administration of interferon-alpha. Patients undergoing renal or hepatic allograft transplantation who develop hepatitis C virus infections are not as likely to benefit from interferon-alpha therapy. These patients may be at risk for allograft rejection during interferon treatment.

Chronic Disease↗
PubMed1996

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.

BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B. METHODS: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS: Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment. CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.

Adult↗
PubMed1996

Infection by hepatitis C virus through contaminated intravenous immune globulin: results of a prospective national inquiry in France.

BACKGROUND: A recent hepatitis C virus (HCV) outbreak has been suspected of being caused by an infusion of intravenous immune globulin. STUDY DESIGN AND METHODS: Three laboratories were mandated by the French regulatory agency to prospectively screen on a national scale those persons having received suspected batches: 233 exposed patients were recalled and tested for HCV antibody and for HCV RNA. RESULTS: Nineteen patients (8.1%) were found positive for HCV RNA; 7 of these 19 were positive for the HCV antibody. CONCLUSION: The link between HCV infection and intravenous immune globulin was reinforced by the overrepresentation of the 2b genotype (58%), which contrasts with the low prevalence of this genotype in France (1%).

Adult↗
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↗