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V Thiers

Publications and source records attributed to V Thiers.

At least 37 records · Page 2Linked to original sources

Effectiveness and tolerance of interferon-alpha 2b in the treatment of chronic hepatitis C in haemodialysis patients.

Twenty-five per cent of haemodialysed patients carry anti-HCV antibodies; these antibodies are associated with detectable viraemia in 85% and chronic hepatitis in 90% of subjects, despite normal transaminases in more than half of them. This underlines the importance of antiviral therapy. We evaluated the tolerance and effectiveness of a classic interferon (IFN) treatment (3 MU three times a week for 6 months, subcutaneously) in 19 haemodialysis patients presenting with anti-HCV antibodies and chronic (n = 16) or acute (n = 3) hepatitis. Thirteen of those 19 patients had elevated transaminases. Viraemia C was detected by genome amplification (PCR) and by the bDNA test before and after interferon therapy as well as 6 months at least after the end of INF treatment. Response (defined as liver enzyme normalization) was noted in 11 (84.6%) of the 13 patients with elevated transaminases; at the end of follow-up, six exhibited long-term response and five had relapsed, HCV-RNA was detected in 15 of the 19 patients before IFN therapy and remained positive in 7/15 initially viraemic patients at the end of treatment. Hepatitis C RNA was detected at the last follow-up visit (mean follow-up duration 18 +/- 9 months) in 12 of the 15 initially viraemic patients. Liver histology was improved in most patients, regardless of their biological response. One patient could not complete the 6-month course because of clinical and haematological adverse events. In the six patients with strictly normal transaminases, HCV RNA was detectable in 4/6 patients before treatment, in 2/4 viraemic patients at the end of treatment, and in 4/4 at the last follow-up visit. All pathological signs disappeared in four of the five patients who had no detectable HCV-RNA before IFN therapy. To conclude: (i) interferon-alpha exhibits satisfactory effectiveness and tolerance in haemodialysed patient; (ii) HCV replication recurs in most of these patients despite histological improvement; (iii) interferon-alpha can be effective even in patients with chronic hepatitis and no detectable HCV-RNA.

Antibodies, Viral↗

The changing relative prevalence of hepatitis C virus genotypes: evidence in hemodialyzed patients and kidney recipients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis. METHODS: Anti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5' untranslated region. RESULTS: Genotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s. CONCLUSIONS: These data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.

Female↗

Evidence of non-A, non-B, non-C infection in chronic hepatitis by polymerase chain reaction testing for hepatitis B and C viruses.

BACKGROUND/AIMS: Although hepatitis C virus is clearly the major cause of non-A, non-B acute and chronic hepatitis, there is a group of patients with histologically documented chronic hepatitis with no serological marker of hepatitis B and C, nor any other risk factors for liver disease. METHODS: We have investigated 17 well-characterized patients with chronic active hepatitis. HBV-DNA and HCV-RNA were tested by polymerase chain reaction in 17 serum samples and in six liver biopsies. RESULTS: Four of the 17 patients had serum HCV-RNA detectable by polymerase chain reaction, while none had HBV-DNA detectable by polymerase chain reaction. Three of the six liver samples gave a positive signal by cyclin A and HLA, and only these were considered for the study. One of the three was HCV-RNA positive, while none was HBV-DNA positive. CONCLUSIONS: Our results, obtained through careful elimination of all known risk factors for liver disease, strongly suggest that non-A, non-B, non-C hepatotropic virus(es) could be involved in some cases of chronic active liver disease.

Adolescent↗

Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of hemodialyzed patients.

A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed patients were given a standard alpha-2b interferon regimen (3 megaunits subcutaneously three times weekly, following each hemodialysis) over six months as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N = 3). Thirteen of these 19 had increased levels of aminotransferase at the time of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the polymerase chain reaction and the bDNA test, respectively, at the beginning and at the end of antiviral treatment, and a third time at least six months after the end of therapy (mean follow-up 18 +/- 9 months). HCV genotype was determined in the 15 patients who had detectable HCV RNA before treatment. The biological response (long-term response, relapse or non-response) was defined as usual according to the serum aminotransferase levels during therapy and at least six months after. A post-treatment liver biopsy, allowing comparison with semiquantitative pathological scores, was performed in 14 patients. Only one of the 19 treated patients did not complete therapy because of poor tolerance, while 18 of the 19 fairly tolerated a complete six month course of alpha-2b interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Serum hepatitis C virus (HCV) RNA: a reliable tool for evaluating HCV-related liver disease in anti-HCV-positive blood donors with persistently normal alanine aminotransferase values.

BACKGROUND: The significance of hepatitis C virus (HCV) antibodies in blood donors with persistently normal alanine aminotransferase (ALT) levels requires evaluation. STUDY DESIGN AND METHODS: The serum and the liver were assayed for HCV RNA. Liver histology was analyzed in 14 HCV-positive subjects who had repeatedly normal ALT values over a follow-up period of at least 3 months. RESULTS: HCV RNA was not detected in liver and serum, and liver histology showed minimal changes in more than one-half of the subjects (8/14), even if third-generation recombinant immunoblot assay was positive; this demonstrated that HCV can be eradicated spontaneously. Moderately histopathological liver lesions were usually found in HCV RNA-positive subjects (6/14), but one subject had active disease that required interferon therapy; this shows that chronic hepatitis may be present in HCV-positive individuals despite repeatedly normal transaminase values. HCV genotypes other than 1b (II) were usually identified, and the presence or absence of serum and liver HCV RNA correlated completely in all 14 patients. CONCLUSION: Serum HCV RNA should be assayed in those HCV-positive donors having repeatedly normal transaminase activity; if it is positive, indicating an ongoing HCV infection, a liver biopsy should be performed to measure the degree of the liver disease and determine the appropriate antiviral therapy.

Adult↗

Comparative analysis of two assays for genotyping hepatitis C virus based on genotype-specific primers or probes.

BACKGROUND/AIMS: The importance of determining the hepatitis C virus genotype has increased since several authors have described a good correlation between hepatitis C virus genotype and response to interferon treatment or to disease severity. It is thus of particular importance to develop reliable assays for hepatitis C virus genotyping. METHODS: We have comparatively analyzed hepatitis C virus genotypes of 208 French and Italian chronically infected patients using genotype-specific primers polymerase chain reaction in the capsid region and a genotype-specific probe-based assay in the 5' untranslated region (LiPA). RESULTS: We found a good concordance between the two assays for the prevalent genotypes in our regions (145/174). The nucleotide sequences in the 5'UTR and capsid domain were investigated to determine the molecular basis of some discordant results. This analysis showed that the genotype-specific probe-based assay gave more consistent results, probably because this technique is based on several probes distributed along the 5'UTR to reveal each genotype. In contrast, the low variability of 5'UTR did not always permit classification of the hepatitis C virus genotype 1 subtypes. We also found some problems, using genotype-specific primers polymerase chain reaction, for less represented genotypes; in particular, in the presence of type 2a/III we obtained more discordant results. This observation is of importance in view of the potential association of this genotype with mild liver disease and a good response to interferon-a treatment.

Base Sequence↗

Post-transfusional anti-HCV-negative non-A non-B hepatitis (II) serological and polymerase chain reaction analysis for hepatitis C and hepatitis B viruses.

Hepatitis C virus (HCV) is a major etilogical agent of post-transfusional and sporadic acute and chronic hepatitis in various geographical areas. However, anti-HCV seroconversion was uncommon in a recent study of patients with post-transfusional hepatitis in Paris, France (N. Asar et al., companion paper). The aim of the present study was to detect viral markers, in particular HCV RNA and hepatitis B virus (HBV) DNA, in these patients. A combination of second-generation assays for anti-HCV antibodies and the polymerase chain reaction were used to identify HCV RNA and HBV DNA sequences in serum samples collected before and after transfusion from patients who developed non-A, non-B hepatitis. Eighteen cases of acute, post-transfusional, non-A, non-B hepatitis were identified in the prospective clinical survey. Only three of these 18 subjects developed anti-HCV antibodies in second-generation tests. HCV RNA was identified in the serum of these three subjects but in none of the others. Two patients who were anti-HCV-negative had polymerase chain reaction evidence of HBV DNA. Known viral markers were not identified in 13 of the 18 patients with acute post-transfusional non-A, non-B hepatitis. These results raise the issue of HCV strains or 'non-A, non-B, non-C' viruses not identified by current HCV and HBV markers and implicated in post-transfusional hepatitis in France.

Base Sequence↗

Complete nucleotide sequence and viral envelope protein expression of a hepatitis B virus DNA derived from a hepatitis B surface antigen-seronegative patient.

An HBV strain isolated from a patient lacking conventional serological markers of HBV infection was characterized. The complete nucleotide sequence was determined following PCR amplification. Only 22 nucleotide substitutions were found relative to the reported sequence of the ayw subtype. Five of these point mutations in the preS/S and preC/C genes led to amino acid substitutions and, with one exception, were located in regions coding for antigenic determinants of viral envelope or capsid proteins. Eight amino acid substitutions were located in terminal protein and the spacer domain of the polymerase gene product. Despite these amino acid changes, transient expression of the preS2 and S envelope proteins in eucaryotic cells yielded viral proteins detectable in the culture medium with polyclonal and monoclonal anti-preS2 and -S antibodies. These data conclusively demonstrate persistent infection by HBV in subjects without HBV serological markers. The absence of conventional HBV serological markers is probably due to several factors: a low level of viral replication, some genetic modifications, as well as an abnormal immune response to the virus.

Animals↗

Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels.

The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV-positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.

Alanine Transaminase↗

Lack of evidence for a role of HCV in hepatitis-associated aplastic anaemia.

Hepatitis-associated aplastic anaemia (HAAA) is usually related to non-A, non-B hepatitis agents but the prevalence of anti-hepatitis C virus (HCV) antibodies is similar in HAAA and aplasia of other origins according to the results of the ELISA 1 assay. This fact could reflect either that HCV is not involved in HAAA or that HAAA-associated defective immune function could yield false negative assays despite on-going HCV infection. To test these hypotheses, we compared 19 patients with HAAA, including three ELISA 1-positive, to 23 patients with aplasia of known and unknown origin, including eight ELISA 1-positive, who were matched for age, sex and blood transfusion units. HCV infection was searched for by the second-generation recombinant-immunoblot assay (RIBA2), and by the polymerase chain reaction which detects HCV viraemia. HCV viraemia was detected in four among the 19 patients with HAAA and in six among the 23 patients with aplasia of other causes. HCV does not clearly appear responsible for hepatitis-associated aplastic anaemia which could be due to non-A, non-B, non-C hepatitis virus. HCV viraemia is frequent in severe aplastic anaemia, even without detectable anti-HCV antibodies, and reflects mainly transfusion-associated HCV infection.

Anemia, Aplastic↗

Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment.

Aged↗

Lack of mother-to-infant transmission of hepatitis C virus in human immunodeficiency virus-seronegative women: a prospective study with hepatitis C virus RNA testing.

The published risk of mother-to-infant transmission of hepatitis C virus varies according to the population studied and the tests used. In a prospective study we used the polymerase chain reaction to assess the risk of vertical transmission of hepatitis C virus in an unselected population of women uninfected by human immunodeficiency virus. Hepatitis C virus antibodies were sought with a second-generation enzyme-linked immunosorbent assay in 2,367 consecutive pregnant women. Forty-one were positive, and 17 consented to serological follow-up of their offspring (n = 18). A second-generation recombinant immunoblot assay, ALT determination and hepatitis C virus RNA testing were performed on maternal sera obtained during pregnancy and sera from the offspring at birth and thereafter. Five older brothers or sisters were also tested. Hepatitis C virus RNA sequences in serum were amplified with a modified nested polymerase chain reaction procedure with primers from the highly conserved 5' noncoding region of the hepatitis C virus genome. All the neonates were positive for hepatitis C virus antibodies, with enzyme-linked immunosorbent assay titers and recombinant immunoblot assay patterns similar to those of their mothers. After birth hepatitis C virus antibodies gradually disappeared within 6 mo. Hepatitis C virus RNA was consistently negative in the 18 children from birth to 24 mo (range = 3 to 24 mo) and in the 5 older children, regardless of the hepatitis C virus polymerase chain reaction status of the mothers (8 of whom were positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy.

After describing two cases of Hashimoto's thyroiditis associated with chronic hepatitis C, we set up a prospective study to assess the prevalence of thyroid autoantibodies (thyroglobulin and thyroid microsomal autoantibodies) in 72 chronic hepatitis C patients (43 men and 29 women; mean age = 51 +/- 2.1 yr) before interferon therapy admitted between January and December 1991 to our liver unit. Thyroid autoantibodies were systematically assayed in 60 chronic HBsAg-positive patients (34 men and 26 women; mean age = 50 +/- 2.2 yr), who served as controls. Antibody to hepatitis C virus was detected with a second-generation enzyme immunoassay and then confirmed with a recombinant immunoblot assay and a supplemental enzyme immunoassay using two beads. In chronic hepatitis C patients, no men had thyroid autoantibodies. Nine of 29 women (31%) had thyroid autoantibodies. Among them, six (20.7%) had high titers of thyroid autoantibodies, and two had hypothyroidism. In all nine of these women, hepatitis C virus viremia was detected on nested polymerase chain reaction (with primers located in the 5' untranslated region). One year later, titers of thyroid autoantibodies had increased in one patient. Three other patients progressed to hypothyroidism. We judged four of 29 patients (13.8%) to have Hashimoto's thyroiditis on the basis of their high titers of thyroid autoantibodies and biological features of hypothyroidism. In the control group, only one man had thyroid microsome autoantibodies, at a very low titer (1:100). The association between chronic hepatitis C and presence of thyroid autoantibodies is clearly confirmed (p = 0.021) by this study.

Autoantibodies↗

Infection of peripheral mononuclear blood cells by hepatitis C virus.

We investigated the infection of peripheral blood mononuclear cells (PBMNC) by hepatitis C virus (HCV) in 5 patients with HCV-related chronic hepatitis. The presence of HCV-RNA-positive and -negative strands was tested with the polymerase chain reaction (PCR) method. In all subjects, HCV-RNA was shown in PBMNC. In 3 cases, HCV-RNA was shown in the T- and B-cell populations, with viral RNA also present in the monocyte-macrophage fraction of two of these. HCV-RNA-negative stranded molecules, indicative of the viral multiplication, were significantly increased in cells maintained in cultures with PHA/PMA stimulation. The results indicate that HCV infect blood mononuclear cells, thus suggesting that this cellular tropism may play a role in HCV infection.

Adult↗

Hepatitis C viremia and anti-HCV antibodies in alcoholics.

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease.

Adult↗

Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction.

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.

Base Sequence↗