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Biomedical subjects

P Opolon

Publications and source records attributed to P Opolon.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of interferon therapy in "non responder" patients with chronic hepatitis C.

We reviewed the impact of interferon treatment on viral load, transaminase serum activity and histological features in patients with chronic hepatitis C in whom treatment did not result in a sustained virus eradication. As patients with cirrhosis are often called non responders, we also reviewed the impact of interferon on these end points as well as on hepatocellular carcinoma incidence and survival. This overview provides evidence that interferon in patients who have not cleared hepatitis C virus (HCV) significantly reduces viral load, serum ALT activity, improves histological activity and blocks progression of fibrosis compared to the natural history of the disease. Thus, patients who still have a positive HCV PCR should no longer be called non responders to interferon. Although the number of randomized trials is limited, there is also cumulative data suggesting that interferon could reduce the incidence of hepatocellular carcinoma incidence and mortality.

Alanine Transaminase↗
PubMed1999

Effect of interferon therapy on the natural history of hepatitis C virus-related cirrhosis and hepatocellular carcinoma.

In patients with chronic hepatitis C who have a sustained virologic response to IFN therapy, there is a dramatic effect on the natural history of the disease, with ALT levels becoming normal, histologic activity improving or disappearing, and the progression of fibrosis slowing. A sustained virologic response 6 months after the end of treatment is predictive of a sustained remission 4 years later. From these results, a long-term survival benefit is expected from IFN treatment in patients with an intermediate or rapid rate of fibrosis. For patients with chronic hepatitis C who do not experience a sustained eradication of virus, there is evidence that IFN treatment significantly reduces the viral load and serum ALT level, improves histologic activity, and blocks fibrosis progression, in comparison with the natural history of this disease. Therefore, patients who still have a detectable level of HCV RNA should no longer be considered nonresponders to IFN therapy. Although the number of randomized trials is [figure: see text] small, cumulative data suggest that IFN therapy can reduce the incidence of and the mortality from hepatocellular carcinoma in patients with cirrhosis.

Alanine Transaminase↗
PubMed1999

Angiogenesis induced in muscle by a recombinant adenovirus expressing functional isoforms of basic fibroblast growth factor.

The present work studies the effects of a replication-deficient adenovirus (Ad), Ad-RSVbFGF, bearing the human basic fibroblast growth factor (bFGF) cDNA, as a potential vector for therapeutic angiogenesis of ischemic diseases. The different isoforms of the protein were expressed from the viral vector in various cell types and, although the cytoplasmic isoform does not possess a signal peptide, we observed its release from a muscle cell line. The proteins were fully functional when tested in a long-term survival assay of quiescent fibroblasts. After endothelial cell infection with Ad-RSVbFGF, we observed an 80&percnt increase in the mean length of the capillary-like tubes that differentiated in a three-dimensional model of angiogenesis. We evaluated angiogenesis directly in mice 14 days after subcutaneous injection of Matrigel plugs containing Ad-RSVbFGF. A marked neovascularization was observed in the Matrigel plugs and in the surrounding tissues. Finally, the recombinant virus was injected into the hindlimb muscles of mdx mice. A 2.5-fold increase in bFGF content of the muscle was observed 6 days after injection, without any significant variations detected in the animal sera. Immunohistological detection showed an increased number of large-caliber vessels in the treated muscles as compared with control muscles. These results demonstrate that Ad-mediated transfer of the human bFGF gene can induce angiogenesis in muscle, making this tissue a potential target for the treatment of ischemic diseases.

Adenoviridae↗
PubMed1999

Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a relevant model system for gene therapy of human prostatic cancer.

This present study evaluates the potential of adenovirus-mediated gene transfer (AMGT) to the prostate of normal laboratory beagles. Many morphological and histological similarities can be noted between dog and human prostate. Moreover, dogs can spontaneously develop prostate cancer with a clinical and biological outcome identical to that in man. Firstly we showed the capacity of human adenovirus to infect canine prostatic cells in vitro. Secondly, we injected transrectally in the dogs' prostates 2x10(9) plaque forming units of a first generation recombinant adenovirus vector harboring the reporter gene beta-galactosidase (AdRSVbetagal). Seven days after the adenoviral delivery, we observed expression of the transgene in both prostates, and exclusively in epithelial cells. Despite a cellular and a humoral immune response, the infusion appeared safe, since the dogs had no fever and presented no urinary symptoms. This study constitutes the first evaluation of AMGT in dog prostate and provides a basis for gene therapy treatment of prostate carcinoma-bearing patients.

Journal Article↗
PubMed1999

Hepatitis B virus (HBV) mutations associated with resistance to lamivudine in patients coinfected with HBV and human immunodeficiency virus.

Mutations associated with hepatitis B virus (HBV) resistance to lamivudine have not been extensively addressed in human immunodeficiency virus (HIV)-HBV coinfection. We have studied the HBV polymerase sequences from nine coinfected patients who experienced HBV recurrence while under lamivudine treatment. In seven of these nine patients, Met(550), belonging to the highly conserved YMDD motif, was mutated to Val and was associated with a substitution of Met for Leu(526) in each case. In the two remaining patients, we found a Met(550)-to-Ile change that was associated in only one case with a Leu(526)-to-Met mutation. No mutation was observed in three control patients not receiving lamivudine. This study demonstrates the emergence of particular genetic profiles in HBV-HIV-coinfected patients experiencing a loss of control of HBV infection despite high doses of lamivudine.

Anti-HIV Agents↗
PubMed1999

Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus.

BACKGROUND: Mixed cryoglobulinaemia is closely associated with hepatitis C virus (HCV) infection. AIM: To assess in a prospective open study the efficiency of interferon alpha treatment of cryoglobulinaemia, as reflected by the disappearance of cryoglobulins and clinical manifestations of the disease, and to analyse the factors predictive of a response to interferon. METHOD: Eighty seven consecutive patients with chronic hepatitis C treated for the first time with interferon at a dose of 3 x 10(6) international units three times a week for six months were studied. Forty three patients had cryoglobulins, which were responsible for clinical manifestations in 12. RESULTS: At the end of interferon treatment, cryoglobulins had disappeared in 39% of the patients. A clinical improvement (except for neuropathies) was observed in all patients. Six months after interferon treatment was stopped, the same rate of response (normal alanine aminotransferase values and undectable HCV RNA) was observed in patients with or without cryoglobulins. Only 14% of patients still had undetectable cryoglobulins, and all of them also had undetectable serum HCV RNA. The disappearance of cryoglobulins was found less frequently in patients with clinical symptoms than in asymptomatic ones, but the difference was not significant. Sustained responders were more often men, infected by genotype 2 or 3, with a lower pretreatment viral load. CONCLUSION: The presence of cryoglobulins does not seem to affect the response to interferon in HCV infected patients. The improvement in cryoglobulinaemia is strongly associated with a virological response, reinforcing the hypothesis of a direct role for HCV in the pathogenesis of this disease.

Adult↗
PubMed1999

Low hepatic iron concentration: evaluation of two complementary methods, colorimetric assay and iron histological scoring.

AIMS: To validate a method of assessment of low hepatic iron concentration based on a biochemical colorimetric assay plus histological scoring. METHODS: The within-day and day to day precision of the iron colorimetric assay was determined on frozen rat liver. The coefficient of variation (CV) of iron measurement in two separate samples from the same liver was determined for 21 deparaffinised human biopsies. The intra- and interlaboratory variability of the colorimetric assay and histological scoring were assessed on 38 deparaffinised liver biopsies. RESULTS: For the within-day test, the CV was 11% (5.1 (0.6) mumol/g dry weight (dw), mean (SD) iron concentration). For the day to day test, the CV was 19.5% (8.2 (1.6) mumol/g dw). The CV was 14.7% for iron concentration determined in two separate samples from the same liver. By correlation and kappa concordance tests, the intra- and interlaboratory variability of the hepatic iron colorimetric assay and iron histological scoring was slight. Absence of stainable iron corresponded to a liver iron concentration < or = 20 mumol/g dw. CONCLUSIONS: A combination of two complementary methods, colorimetric measurement and histological scoring, is an accurate and reliable way of determining low iron concentrations in deparaffinised human liver biopsies. In secondary haemosiderosis, such methods would be essential for investigating the role of low iron overload in fibrogenesis and during the response to antiviral treatment in chronic viral hepatitis.

Animals↗
PubMed1998

Heart-specific targeting of beta-galactosidase by the ventricle-specific cardiac myosin light chain 2 promoter using adenovirus vectors.

Adenoviruses are attractive vectors for gene transfer into cardiac muscle. However, their promiscuous tissue tropism, which leads to an ectopic expression of the transgene, is a considerable limitation. To restrict expression to cardiomyocytes, we have constructed two recombinant adenoviruses (Ad-MLC2-250betagal and Ad-MLC2-2100betagal) containing the beta-galactosidase reporter gene under the control of the 250- or 2100-bp rat ventricle-specific cardiac myosin light chain-2v promoter (MLC-2v). Our in vitro and in vivo data have evidenced that the 2100-bp promoter allows stronger beta-galactosidase activity than the 250-bp promoter and that the deleted promoter allows a weak beta-galactosidase expression in skeletal muscle-derived cells in vitro. In contrast to the in vitro results, the highly deleted MLC-2v promoter of 250 pb conserved its heart specificity in in ovo and in vivo when introduced into the adenovirus genome, indicating that the specificity of this promoter is neither altered by the inverted terminal repeat nor by the enhancer of the Ela promoter, both of which located in the 5' flanking region of the promoter. Systemic injections of both recombinant adenoviruses into chicken embryos showed beta-galactosidase expression mainly in the right ventricle of the heart. We have confirmed the cardiac specificity of both promoters in mammalian species after injection of both recombinant adenoviruses into the heart of adult rats in vivo. The comparison of both promoters in vitro and in vivo has shown that the 250-bp MLC-2v promoter is 80% less active than the 2100-bp MLC-2v promoter and has enabled us to conclude that the MLC-2v promoter of 2100 bp is the most appropriate for efficient expression of a reporter gene or a therapeutic cardiac gene (e.g., SERCA2a or minidystrophin gene).

Adenoviridae↗
PubMed1998

Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients.

For understanding the local immune response in human non-small cell lung cancer (NSCLC), we investigated both Th1 and Th2-type as well as TGF-beta1 cytokine mRNA expression in 10 fresh tumor biopsies, the corresponding tumor and short term TIL cell lines as well as patient PBMC. A methodology based on a highly sensitive quantitative RT-PCR was used. We found that IL-6 mRNA was highly expressed in all tumor biopsy samples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I cytokines revealed a low expression level of IL-2 mRNA, while IFNgamma and GM-CSF expression was high in the majority of the tumor lesions studied. Quantitatively, high amounts of Th2-type cytokine mRNA were detected at the tumor site with IL-6 as the predominant lymphokine. A high mRNA expression level of the immunosuppressive cytokine TGF-beta1 was observed in all NSCLC. To identify the cell types responsible for the production of TGF-beta1, IL-6, IL-10 and GM-CSF at the tumor site, tumor and TIL cell lines were derived from the corresponding biopsies. All the 3 tumor cell lines analysed were found to express high amount of TGF-beta1 but not IL-10 mRNA, 2 expressing IL-6 and GM-CSF. Five short term TIL cell lines established in the presence of IL-2 expressed high level of IL-10, IL-4 and IFNgamma but not IL-2 mRNA. Strikingly, high expression of IL-10 mRNA was also observed in all 6 patient PBMC analyzed as compared to controls. Together, our results indicate the existence of a local and peripheral Th-2-type cytokine pattern in patients bearing NSCLC.

Aged↗
PubMed1998

Angiostatin gene transfer: inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest.

The antitumoral effects that follow the local delivery of the N-terminal fragment of human plasminogen (angiostatin K3) have been studied in two xenograft murine models. Angiostatin delivery was achieved by a defective adenovirus expressing a secretable angiostatin K3 molecule from the cytomegalovirus promoter (AdK3). In in vitro studies, AdK3 selectively inhibited endothelial cell proliferation and disrupted the G2/M transition induced by M-phase-promoting factors. AdK3-infected endothelial cells showed a marked mitosis arrest that correlated with the down-regulation of the M-phase phosphoproteins. A single intratumoral injection of AdK3 into preestablished rat C6 glioma or human MDA-MB-231 breast carcinoma grown in athymic mice was followed by a significant arrest of tumor growth, which was associated with a suppression of neovascularization within and at the vicinity of the tumors. AdK3 therapy also induced a 10-fold increase in apoptotic tumor cells as compared with a control adenovirus. Furthermore, we showed that systemic injection of AdK3 delayed C6 tumor establishment and growth, confirming that angiostatin can function in a paracrin manner. Our data support the concept that targeted antiangiogenesis, using adenovirus-mediated gene transfer, represents a promising alternative strategy for delivering antiangiogenic factors as their bolus injections present unsolved pharmacological problems.

Adenoviridae↗
PubMed1998

Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity.

In hepatitis C virus (HCV) patients with persistently normal alanine transaminase (ALT), the progression rate of fibrosis is unknown. The aims of this study were: 1) to compare HCV patients with normal ALT (group I) with HCV patients with elevated ALT (group II) matched on independent factors associated with fibrosis; and 2) to assess the progression rate of fibrosis. One hundred two HCV patients were included in each group. Histological lesions were staged using the METAVIR score. We defined fibrosis progression per year as the ratio of the fibrosis stage in METAVIR units to the duration of infection. In group I, ALT values were normal, and lower than in group II (25 vs. 127 IU/L; P < .0001). HCV RNA was present less frequently in group I (66% vs. 97%; P < .0001). There were no significant differences for viremia and genotypes. Histological activities were lower in group I (0.6 vs. 1.38; P < .0001). The stage of fibrosis was lower in group I (0.95 vs. 1.8; P < .001). The median progression rate of fibrosis was lower in group I (0.05 vs. 0.13; P < .001). In group I, after exclusion of negative HCV-RNA patients, the median progression rate of positives remained lower (0.05 vs. 0.13; P < .001). In group I, all cirrhotic patients (n = 3) were heavy drinkers. HCV patients with normal ALT showed weaker histological activity and lower fibrosis scores, and the progression rate of fibrosis was twice as slow as in HCV patients with elevated ALT. In these patients, severe fibrosis was associated with high alcohol consumption.

Adolescent↗
PubMed1998

Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group.

In clinical research, the definition of the upper limit of normal (ULN) alanine transaminase (ALT) is never detailed. However, such a definition can vary and may have practical consequences. Our aim was to assess factors associated with serum ALT activity in apparently healthy subjects and then to apply seven different definitions of ULN in three different populations so as to assess the prevalence of subjects with normal ALT among blood donors and among hepatitis C patients before (normal ALT hepatitis C patients) and after treatment (interferon [IFN] responders). ALT measurements were performed in the same laboratory using the same technique; 1,033 donors were prospectively investigated, 186 patients with hepatitis C never treated and 40 patients treated with 3 MU three times per week of IFN-alpha for at least 6 months. The seven definitions (D) of ULN were: D1: 95th percentile of ALT; D2: 95th percentile after separating males and females; D3: males and females separately, ULN=10 (mean of log10 ALT + 1.96 SD); D4: ULN=45 IU/L given by the manufacturer; D5: mean + 1 SD after exclusion of the 5% extreme values; D6: 95th percentile after separating subjects with body mass index (BMI) under or equal to the median (23); and D7: 95th percentile after separating subjects according to BMI and sex. BMI and male sex were independently associated (P < .0001; logistic regression) with ALT, without an association with alcohol. The range of ULN varied from 26 IU/L in females (D5) to 66 IU/L in males with BMI >23 (D7). Depending on the definition, the prevalence of blood donors with normal ALT varied from 82% to 96%, i.e., a range of 14%; that of hepatitis C patients with normal ALT varied from 16% to 27%, i.e., a range of 11%; the prevalence of IFN responders varied from 25% to 42%, i.e., a range of 17%. Definitions of normal ALT values should be adjusted for sex and BMI to reduce artificial heterogeneity in blood donor selection and in hepatitis C clinical studies.

Adult↗
PubMed1998

Mutations in NS5A region of hepatitis C virus genome correlate with presence of NS5A antibodies and response to interferon therapy for most common European hepatitis C virus genotypes.

A part of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) amino acid sequence, designated as an interferon (IFN)-sensitive determining region (ISDR), has been shown to be correlated with a response to IFN in Japanese patients. We have shown previously that the presence of NS5A antibodies (Abs) detected by the INNOLIA test (IL-NS5A Ab) is also correlated with a response to IFN. The aim of this study was to investigate, in a wide range of patients, the possible relationship within the NS5A protein between the sequence of ISDR and that used in the INNOLIA test designated as IL3R. Serum samples from 52 patients infected by HCV genotypes 1, 2, and 3 were analyzed before and after treatment. The patients were classified as nonresponders (NRs), responder-relapsers (RRs), or long-term responders (LTRs). We amplified the NS5A region for 42 patients using polymerase chain reaction (PCR), and these amplicons were sequenced directly. The 10 remaining patients were analyzed using PCR with mutation-specific primers. No correlation was found between the IL3R sequence of the HCV strains and the presence of the IL-NS5A Ab for all genotypes. However, for the subtype 1b, only 2 of 11 NR patients tested had an arginin in position 2218 within the ISDR versus 3 of 3 LTR and 10 of 13 RR patients. All patients with R-2218 had IL-NS5A Ab. For the genotype 1a, 2 of 2 LTR and 1 of 3 RR were mutated in position 2216-2218 in comparison to three NR sequences. For the genotype 3, no mutations were found in the region homologous to 1b-ISDR, but 4 of 5 LTR and RR patients had a mutation T-2161 to A or V versus 0 of 3 NR patients. A close correlation was found between arginin in position 2218 in ISDR, the presence of IL-NS5A Ab, and the response to IFN therapy for genotype 1b, but this association did not predict a long-term response. For genotype 3, a potential ISD mutation could be located at the codon 2161.

Amino Acid Sequence↗
PubMed1998

Pattern of HCV antibodies with special reference to NS5A reactivity in HCV-infected patients: relation to viral genotype, cryoglobulinemia and response to interferon.

BACKGROUND/AIMS: We aimed to compare the anti-hepatitis C virus reactivity in confirmatory assays (RIBA 3.0 Ortho Diagnostic and INNO-LIA HCV Ab III Innogenetics) among patients infected with different hepatitis C virus genotypes, with or without cryoglobulinemia, and in patients treated with interferon. METHODS: One hundred and three patients followed in our hepatogastroenterology unit were included in the study and compared to 320 consecutive patients tested using RIBA 3.0. Seventy-nine of the 103 patients were treated with interferon. Long-term responders to interferon were defined as having normal alanine aminotransferase levels and being HCV RNA negative 6 months after the end of treatment. Initial responders were defined as having normal alanine aminotransferase levels at the end of interferon therapy but abnormal alanine aminotransferase levels and/or detectable HCV RNA during the following 6 months. Non-responders were defined as still having elevated alanine aminotransferase during and after interferon. Serological tests (RIBA and INNO-LIA) were performed according to the manufacturers' instructions. HCV RNA was detected by nested polymerase chain reaction. Hepatitis C virus genotype was determined by using a Line Probe Assay (Innogenetics). RESULTS: There was no significant difference in the pattern of hepatitis C virus reactivity according to the hepatitis C virus genotype or presence of cryoglobulinemia. Twenty-three patients were classified as non-responders, 35 as initial responders, 21 as long-term responders. NS5 reactivity was significantly different (p<0.01) between these three groups: 34% of non-responders (8/23) had RIBA 3.0 NS5 reactivity and 13% (3/23) were reactive in the INNO-LIA III. Almost all long-term responders (95%) had NS5 reactivity by both RIBA 3.0 and INNO-LIA III. CONCLUSION: We conclude that patients who respond to interferon have stronger reactivity against NS5 antigens than non-responders. Molecular changes in the NS5A region may be responsible for such differences, as recently suggested.

Antiviral Agents↗
PubMed1998

Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice.

AdmATF is a recombinant adenovirus encoding a secreted version of the amino-terminal fragment (ATF) of murine urokinase (uPA). This defective adenovirus was used in three murine models to assess the antitumoral effects associated with local or systemic delivery of ATF, a broad cell invasion inhibitor that antagonizes uPA binding to its cell surface receptor (uPAR). A single intratumoral injection of AdmATF into pre-established MDA-MB-231 human breast xenografts grown in athymic mice, or into pre-established C57/BL6 syngeneic Lewis lung carcinoma resulted in a specific arrest of tumor growth. Neovascularization within and at the vicinity of the injection site was also suppressed, suggesting that AdmATF inhibited primary tumor growth by targeting angiogenesis. AdmATF also interfered with tumor cell establishment at distant sites: (1) lung dissemination of Lewis lung carcinoma cells was significantly reduced following intratumoral injection at the primary site; and (2) systemic administration of AdmATF inhibited subsequent liver metastasis in a LS174T human colon carcinoma xenograft model. These data outline the potential of using a recombinant adenovirus directing the secretion of an antagonist of cell-associated uPA for cancer gene therapy.

Adenoviridae↗
PubMed1998

Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?

BACKGROUND: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist. AIM: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials. METHODS: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen. RESULTS: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant. CONCLUSIONS: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

Administration, Cutaneous↗
PubMed1998

No evidence for abnormal immune activation in peripheral blood T cells in patients with hepatitis C virus (HCV) infection with or without cryoglobulinaemia. Multivirc Group.

The aim of this study was to investigate the peripheral blood lymphocyte (PBL) phenotypes and T cell repertoire in patients with HCV infection, with or without mixed cryoglobulinaemia (MC). The patients were: Group 1, 23 patients with HCV infection and MC; Group 2, 14 patients with HCV infection but without MC; Group 3, 10 patients with symptomatic essential MC. Twenty healthy blood donors were used as controls. Blood lymphocyte counts were determined, and flow cytometry was used to measure proportions of B cells (CD19+), natural killer (NK) cells (CD16+CD56+), T cells (CD3+), CD4+ T cell subsets (memory CD4+CD45RO+; naive CD4+CD45RO-; Th0/Th2CD4+CD7-; activated CD4+CD25+), and CD8+ T cell subsets (immunoregulatory CD8+CD57+; cytotoxic CD8+S6F1+, activated CD8+CD25+). Bias in the usage of T cell receptor (TCR) Vbeta chains was studied in a subgroup of 10 representative patients of Group 1 using a polymerase chain reaction (PCR) analysis of the Vbeta segments with a series of 20 oligonucleotides specific for the Vbeta families. The three groups were comparable for blood lymphocyte counts, and we observed no abnormal repartition of the following PBL subsets: T cells (CD3+), CD4+ and CD8+ subpopulations, B cells (CD19+), and the NK cells (CD16+56+). In none of the groups could we observe lymphocyte ex vivo activation as assessed by the normal expression of the activation cell markers: CD25 on CD4+ or CD8+ T cells, or CD5 on B cells. The repartition of naive and memory (CD45RO-/RO+) CD4+ T cells was normal and we did not observe any amplification of the CD4+CD7- T cell subset differentiated in vivo in Th0/Th2 cells. There was no significant amplification of cytotoxic (SF6+) and immunoregulatory (CD57+) CD8+ T cells in HCV patients with or without MC. Finally, the usage of Vbeta families in the TCR repertoire was normal in the patients tested. In patients with chronic HCV infection, with or without MC, we did not find any significant expansion or abnormal activation of T, B and NK cell subsets, dysbalance of the naive/memory subsets, or expansion of the Th0/Th2 subpopulation. These findings differ from the profound immune alterations that are observed in other chronic infections such as HIV or Epstein-Barr virus. Although this study was restricted to the peripheral blood, it suggests that in chronic HCV infection, MC is not the consequence of a chronic activation or dysregulation of the peripheral blood immune cells.

Adult↗