Non-insulin-dependent diabetes mellitus developing during interferon-alpha therapy for chronic hepatitis C.
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Antiviral Agents↗
Biomedical subjects
N Boyer
Publications and source records attributed to N Boyer.
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↗
Changes in plasma membrane fluidity of Bryonia dioica internodes during thigmomorphogenesis.
Fluidity changes in plasma membrane (PM) lipid extracts or native membranes isolated from Bryonia dioica internodes after a mechanical stimulation were monitored by steady-state fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. The signal was shown to rapidly induce an increase in the bulk lipid fluidity. This event was closely related to a relative enrichment in some phospholipid species (PC, PG and PS) as well as a significant increase in the unsaturation index of total fatty acyl chains. Free sterols and protein content did not appear to be involved into this process. After 48 h, lipids from rubbed internodes became less fluid than PM lipids from control internodes.
Cell Membrane↗
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↗
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↗
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↗
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↗
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↗
[Factors of response to treatment with interferon-alpha in patients with chronic hepatitis C. Therapeutic perspectives].
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Age Factors↗
Retreatment with interferon-alpha of chronic hepatitis C virus infection.
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Adult↗
Long-term histologic and viral changes in patients with chronic hepatitis C who responded to alpha interferon.
We assessed the long-term outcome in 24 patients with chronic hepatitis C who responded to alpha interferon. All patients were followed up for 12 months, and 16 patients were followed up 41 +/- 9 months. During the follow-up period, 18 of the 24 patients (75%) relapsed (serum ALT levels increased again); 16 had an early relapse within the 6 months and two had a late relapse 21 and 36 months after therapy; one cirrhotic patient with relapse died. Serum HCV RNA remained detectable in the two patients before the late relapse and in three of the six patients with sustained biochemical response. Histologic assessment 13 to 31 months after therapy showed a decrease in activity in most patients, even in some of those with relapse, but the decrease in portal inflammation was more marked (p < 0.05) in patients with sustained biochemical response. Liver HCV RNA was not detectable in the two sustained responders who were negative for serum HCV RNA. Despite biochemical remission induced by interferon therapy, HCV replication persists in many patients with a potential risk of late relapse. In contrast, some patients have no long-term detectable HCV RNA, suggesting clearance of HCV. Long-term histologic improvement of portal inflammation in most patients confirms the beneficial effect of interferon.
Adult↗
Isolation, sequencing and analysis of the expression of Bryonia calmodulin after mechanical perturbation.
A cDNA clone (Bc329) encoding calmodulin was isolated from a Bryonia cDNA library by screening with cloned Arabidopsis calmodulin cDNA. The cDNA Bc329 was 899 bp full-length clone. The predicted amino acid sequence consists of 149 residues and reveals a high homology with other known plant calmodulins (91 to 99% identity). Genomic southern blot suggests that Bryonia calmodulin is encoded by a single-copy gene. The Bc329 clone was used as a probe to study the expression of calmodulin mRNA after a mechanical stimulus applied on young Bryonia internodes. The steady-state of calmodulin mRNA reached a maximum 30 min after the treatment before it progressively decreased. The role of calcium and calmodulin as second messengers is discussed with regard to environmental changes.
Amino Acid Sequence↗
Cytological indication of the involvement of calcium and calcium-related proteins in the early responses of Bryonia dioica to mechanical stimulus.
The distribution of membrane-bound calcium, activated calmodulin, and callose synthesis was visualized in Bryonia dioica internodes before and after mechanical stimulus, using fluorescent probes, respectively, chlorotetracycline, fluphenazine, and aniline blue. Bright chlorotetracycline fluorescence remains localized in the plasma membrane of control cells, 30 s after stimulation calcium left the plasmalemma. A delocalization of activated calmodulin was observed after wounding and deposition of callose, which could not be detected before, appeared in the same times in most cells. The callose formation and the decrease in membrane-associated calcium suggest a rapid influx of calcium in the cytosol and an intervention of this ion in the cascade of the early events underlying Bryonia dioica thigmomorphogenesis.
Calcium↗
Cryoglobulinemia with vasculitis associated with hepatitis C virus infection.
Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the four-antigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis.
Adult↗
Retreatment with recombinant interferon-alpha in patients with chronic hepatitis C.
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Adult↗
Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine.
In this pilot study of the effects of interferon alfa in 10 anti-HIV positive, chronic hepatitis B patients treated with zidovudine (AZT), tolerance to interferon was good and similar to that in anti-HIV negative patients. After treatment, the HIV stage and CD4 lymphocyte count were unchanged. In two patients hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) disappeared and the serum alanine aminotransferase (ALT) returned to normal; loss of hepatitis B surface antigen (HBsAg) with absence of histopathological activity was observed after treatment in one of these patients. These preliminary results need to be confirmed by a larger study.
Adult↗
Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to anti-HBs seroconversion in patients with chronic hepatitis B.
The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.
Adult↗
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↗