Biomedical subjects

Vincent Thibault

Publications and source records attributed to Vincent Thibault.

At least 19 recordsLinked to original sources

PubMed2006

A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C.

BACKGROUND: FibroTest, a noninvasive method of measuring biomarkers of liver fibrosis, is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus (HCV) infection. We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection. METHODS: Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospective cohort of 537 patients. Disease classification at baseline was 157 patients with severe fibrosis (FibroTest >0.58), 137 with moderate fibrosis (FibroTest 0.32-0.58), and 243 with no or minimal fibrosis (FibroTest <0.32). RESULTS: In 64 untreated patients with severe fibrosis, survival without HCV complications was 73% [95% confidence interval (CI), 59%-086%; 13 complications], and survival without HCV-related death was 85% (95% CI, 73%-96%; 7 HCV deaths). Survival rates were higher in patients with moderate fibrosis, [99% (95% CI, 97%-100%; 1 complication; P <0.001) and 100% (no HCV death; P <0.001) for patients with and without HCV-related complications, respectively], and in patients with minimal fibrosis [100% (no complication; P <0.001 vs severe) and 100% (no HCV death; P <0.001 vs severe), respectively]. FibroTest was a better predictor than biopsy staging for HCV complications, with area under the ROC curves (AUROC) = 0.96 (95% CI, 0.93%-0.97%) vs 0.91 (95% CI, 0.85%-0.94%; P = 0.01), respectively; it was also a better predictor for HCV deaths: AUROC = 0.96 (95% CI, 0.93%-0.98%) vs 0.87 (95% CI, 0.70%-0.94%; P = 0.046), respectively. The prognostic value of FibroTest was still significant (P <0.001) in multivariate analyses after taking into account histology, treatment, alcohol consumption, and HIV coinfection. CONCLUSION: The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.

Alanine Transaminase↗

PubMed2006

Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients.

BACKGROUND: Treatment of acute hepatitis C (HCV) in HIV-infected patients has been poorly addressed. OBJECTIVE: To evaluate the efficacy and tolerability of a 24 week course of pegylated interferon alfa 2a (PegIFNalpha2a) and ribavirin for the treatment of acute HCV infection in HIV-infected patients. METHODS: This was a prospective pilot study of 25 consecutive HIV-infected men with acute HCV infection defined by documented HCV seroconversion to anti-HCV positive antibody and positive qualitative HCV RNA measurement. Patients with detectable HCV RNA (> 50 IU/ml) 12 weeks after diagnosis were offered treatment with PegIFNalpha2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks. Sustained virological response was defined by a negative qualitative HCV RNA measurement 24 weeks after the end of treatment. RESULTS: At baseline, 23 patients were taking HAART, 23 patients had HIV RNA < 200 copies/ml and a median CD4 count of 345 cells/microl. Only one patient, with genotype 3 HCV, had a spontaneous clearance of HCV RNA. Of the remaining 24 patients, four refused anti-HCV therapy, ribavirin was contraindicated in one and 19 initiated anti-HCV therapy. Median time between acute HCV diagnosis and initiation of study treatment was 14 weeks. Of the 14 patients who have achieved the post-treatment follow-up at 24 weeks, 10 had a sustained virological response (71%). Study treatment was well tolerated, with no change in CD4 cell count. CONCLUSION: Early treatment of acute HCV infection with PegIFNalpha2a and ribavirin for 24 weeks yields a high sustained virological response rate in HIV-infected patients.

Acute Disease↗

PubMed2006

Changing electrolyte and acido-basic profile in HIV-infected patients in the HAART era.

BACKGROUND: HIV-infected patients may develop a variety of underreported metabolic abnormalities that may be classified into HIVAN, specific HIV abnormalities, coincidental renal disorders and anti-retroviral-treatment-induced side effects. METHODS: Our descriptive cross-sectional study evaluates the prevalence of electrolyte and acid base disorders in HIV patients in the HAART era in a tertiary care teaching hospital. All consecutive HIV-infected patients (n = 1,232) presenting at our Department of Infectious Disease over 3 months were included. MEASUREMENTS: All available biochemical data obtained at admission or on the day of the visit were analyzed. We identified risk factors for electrolyte and acid base disorders with univariate regression analysis and multivariate stepwise regression analysis. Variables tested for significance included age, sex, absolute CD4 and CD8 counts, hepatitis B and C antibodies, and use and type of anti-retroviral medication. RESULTS: Most frequent and clinically relevant abnormalities were hyperuricemia in 41.3%, hypophosphatemia in 17.2% and low bicarbonate level in 13.6% of HIV-tested patients. Plasma magnesium was out of the normal range in 38.9% and blood glucose in 25.3% of the tested patients. When CD4 count was below 200/mm3, 9.2% of tested patients experienced low serum calcium (vs. 0.5% if CD4 count >200/mm3, p < 0.002), 11.4% increased creatinine plasma level (vs. 2.3% if CD4 count >200/mm3, p < 0.0001) and 24.5% low serum bicarbonate (vs. 13.7% if CD4 count >200/mm3, p < 0.0001). Protease inhibitor treatment was a significant risk factor of hyperuricemia (p < 0.003). Non-nucleoside reverse transcriptase inhibitor therapy was significantly associated with less hyperuricemia (OR = 0.6, 95% CI 0.38-0.96) and with hypophosphatemia (OR = 2.0, 95% CI 1.1-3.4). CONCLUSIONS: The profile of biochemical abnormalities in HIV-infected patients has changed, hyperuricemia and hypophosphatemia being the most prevalent. Causes are poorly understood. Interpretation of drug-induced side effects in the HIV patient is only meaningful if performed versus a control group of patients.

Acid-Base Equilibrium↗

PubMed2006

Successful rescue therapy with tenofovir in a patient with hepatic decompensation and adefovir resistant HBV mutant.

BACKGROUND: Prolonged adefovir therapy exposes to the emergence of adefovir resistant hepatitis B virus mutants. Initial reports of the rtN236T mutation showed preserved sensitivity to lamivudine; however, complex mutations are emerging with reduced susceptibility to lamivudine. CASE PRESENTATION: After 2 years of therapy, a cirrhotic patient developed the rtN236T and rtA181T adefovir resistant mutations. He had been previously treated with lamivudine, developed lamivudine resistance and, despite good compliance, had an incomplete response to adefovir. Adefovir resistance resulted in viral breakthrough with hepatitis flare-up and liver decompensation. Tenofovir had an excellent antiviral effect allowing sustained control of viral replication and reversal of hepatic failure. CONCLUSION: In patients with cirrhosis, adefovir resistance can lead to severe hepatitis. Tenofovir appears to be an effective treatment of adefovir resistant mutants. Incomplete control of viral replication with adefovir requires monitoring for viral resistance and should prompt a change in antiviral treatment.

Journal Article↗

PubMed2006

Antiviral therapy for hepatitis C virus--associated mixed cryoglobulinemia vasculitis: a long-term followup study.

OBJECTIVE: To evaluate the long-term efficacy of anti-hepatitis C virus (HCV) therapy in patients with HCV-associated mixed cryoglobulinemia (HCV-MC) vasculitis and to assess the factors associated with clinical remission of MC. METHODS: This was a single-center study of 72 consecutive patients who received treatment with IFN alfa-2b (3 million IU 3 times a week; n = 32 patients) or PEGylated IFN alfa-2b (PEG-IFN alfa-2b) (1.5 mug/kg/week; n = 40 patients), both in combination with oral ribavirin (600-1,200 mg/day), for at least 6 months. Logistic regression was used to assess factors associated with clinical remission of MC. RESULTS: The mean +/- SD duration of followup after discontinuation of antiviral therapy was 39.7 +/- 24.4 months. Eight deaths (11.1% of patients) occurred during the study, primarily as a result of cardiovascular disease, liver disease, or infection. A complete clinical response of the MC occurred in 45 patients (62.5%), a sustained virologic response occurred in 58.3%, and cryoglobulins cleared in 45.8%. Compared with patients treated with IFN alfa-2b plus ribavirin, those receiving PEG-IFN alfa-2b plus ribavirin had a higher sustained clinical (67.5% versus 56.3%), virologic (62.5% versus 53.1%), and immunologic (57.5% versus 31.3%) response, regardless of HCV genotype and viral load. In multivariate analyses, an early virologic response (odds ratio 3.53 [95% confidence interval 1.18-10.59]) was independently associated with a complete clinical response of MC. A glomerular filtration rate <or=70 ml/minute (odds ratio 0.18 [95% confidence interval 0.05-0.67]) was negatively associated with a complete clinical response of MC. CONCLUSION: PEG-IFN alfa-2b plus ribavirin should be considered as induction therapy for HCV-MC vasculitis. An early virologic response and the absence of renal insufficiency are the key factors in the clinical response.

Aged↗

PubMed2006

Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease?

BACKGROUND: Few data are available on chronic hepatitis C (CHC) in elderly patients. The aim of this study was to compare the features and severity of CHC and the efficacy/safety of antiviral therapy in patients<65, between 65 and 80, and >80 yr old, and to determine the usefulness of biochemical markers (Fibrotest-Fibrosure/ActiTest [FT-AT]) in aged patients. METHODS: This was a retrospective study with two groups of patients: Group 1: prospective cohort including all hepatitis C virus patients from our institution (N=4,182); Group 2: all consecutive patients who had FT-AT performed in France between 2002 and 2004 (N=33,738). RESULTS: A total of 6,865 patients>or=65 yr old was included (Group 1=881, Group 2=5,984). Group 1: patients>or=65 had a longer duration of and a higher age at infection, more genotype 1, and a history of transfusion (p<0.001). Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2,F3,F4) was more frequent in patients>or=65 yr old, regardless of the duration of infection. In multivariate analysis, ages at biopsy and at infection were associated with F2,F3,F4. Discovery of CHC by a complication was more frequent in patients>or=65 yr (p<0.001). One hundred seventy patients>or=65 yr received antiviral therapy. A sustained virologic response was obtained in 45% of patients>or=65 yr treated with pegylated interferon/ribavirin. Group 2: At FT, 58% of patients>80 yr, 37% of patients between 65 and 80 yr, and 14% of patients<65 yr (p<0.001) had cirrhosis. Patients>80 yr (43%) with cirrhosis had nonelevated alanine amino transferase (ALT), compared with 31% of patients<65 yr (p<0.001). CONCLUSION: In patients>or=65 yr, CHC is more severe and presents with lower ALT than in younger patients. Treatment is effective. Biochemical markers seem particularly useful as a noninvasive alternative to liver biopsy in this population.

Aged↗

PubMed2006

Expertise of laboratories in viral load quantification, genotyping, and precore mutant determination for hepatitis B virus in a multicenter study.

A national evaluation study was performed in 14 specialized laboratories with the objective of assessing their capacities to provide (i) hepatitis B virus (HBV) viral loads (VL), (ii) HBV genotypes, and(iii) identification of precore/core mutants. The panel consisted of 12 HBV DNA-positive samples with VLs from 2.8 to 9.1 log(10) copies/ml, different HBV genotypes (A to F), and 3 mutant and 9 wild-type samples at nucleotide 1896. The coefficients of variation of the mean VLs ranged from 2.4% to 10.4% with the Cobas HBV Monitor assay, from 1.8% to 5.5% with the Cobas TaqMan 48, from 1.5 to 26.2% with RealArt HBV PCR, and from 0 to 7% with branched DNA (bDNA). The Cobas Monitor assay underestimated the VLs of genotype F samples, with differences ranging from 1.4 to 2.4 log(10) copies/ml. The accuracies of genotype determinations ranged from 33% to 100%, and those of precore mutant determinations ranged from 25 to 100%. This study showed some drawbacks of two widely used assays: (i) Cobas Monitor has a narrow dynamic range and underestimates genotype F sample VLs and (ii) bDNA shows poor sensitivity and may fail to identify patients with low VLs. With higher performance in terms of analytical sensitivity combined with a larger dynamic range and an ability to quantify the main genotypes equally, real-time PCR methods appear more appropriate for accurate monitoring of HBV DNA quantification. Furthermore, the clinical implications of HBV genotyping and the determination of precore/core mutants need to be clearly stated to justify the standardization of these methods.

France↗

PubMed2006

Unique NS5b hepatitis C virus gene sequence consensus database is essential for standardization of genotype determinations in multicenter epidemiological studies.

A multicenter study of NS5b hepatitis C virus (HCV) genotype determination involving 12 laboratories demonstrates that any laboratory with expertise in sequencing techniques would be able to provide a reliable HCV genotype for clinical and epidemiological purposes as long as they are provided a consensus reference sequence database.

Consensus Sequence↗

PubMed2006

Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of "a" determinant variants.

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P = 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

Carrier State↗

PubMed2005

Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1.

BACKGROUND/AIMS: Adefovir dipivoxil (10 mg once-daily) was added to antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients. METHODS: Parameters evaluated included alanine aminotransferase (ALT), HBV DNA and serological markers, HIV-1 RNA, and CD4+ cell count. RESULTS: Twenty-nine patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76 log10 copies/mL (median) to 4.68, 5.24, and 5.90 log10 copies/mL at weeks 48, 96, and 144, respectively (P<0.0001 at all time points). Seven patients (25%) achieved HBV DNA<2.3 log10 copies/mL. No adefovir-associated resistance mutations in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined from 81 IU/L (median) at baseline by -16.0, -44.5, and -46.0 IU/L at week 48, 96 and 144, respectively (P=<0.05, respectively), and normalized in 71% of patients (20 of 28) by week 144. Two patients developed antibodies against HB 'e' antigen by week 48. No serious adverse events related to adefovir dipivoxil occurred during the study, and HIV-1 RNA and CD4+ cell counts were stable. CONCLUSIONS: Treatment with adefovir dipivoxil for 144 weeks was well tolerated and resulted in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected patients. Efficacy increased with treatment duration, with no loss of viral suppression.

AIDS-Related Opportunistic Infections↗

PubMed2005

Hepatitis B virus genotypes and extrahepatic manifestations.

BACKGROUND/AIMS: This study aimed at correlating the presence of extrahepatic manifestations with hepatitis B virus (HBV) genotypes in patients with chronic HBV infection. METHODS: This was a national (France), multicenter, retrospective, cross-sectional study. HBV genotypes were determined in 190 patients HBsAg-positive for at least 6 months and documented before any treatment. RESULTS: Patients were aged 42+/-15 years and mainly male (77%). Alcohol intake was high in 6% of them, ALT elevated in 73%; 27% were cirrhotic. All HBV genotypes were found, mainly A (24%), D (29%), C (11%), and E (10%). Thirty (16%) patients had clinical extrahepatic manifestations, mainly sensory-motor deficiency, sicca syndrome, myalgia, glomerulonephritis, and arthralgia-arthritis. Their presence was not related to any epidemiologic, viral (including genotypes) or hepatic factor, but to a higher platelet count (P=0.004). Twenty-nine (15%) patients had biological extrahepatic manifestations, mainly anti-smooth muscle, antinuclear, and anti-nucleosome antibodies. Their presence was related only to anti-HBe antibodies positivity (P=0.007) or elevated platelet count (P=0.003). Carrying precore mutant HBV increased by 2.8 folds the risk to have at least one extrahepatic biological manifestation. CONCLUSIONS: No relationships between HBV genotypes and the presence of extrahepatic manifestations were evidenced in patients with chronic HBV infection.

Adolescent↗

PubMed2005

Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.

OBJECTIVES: The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression. METHODS: Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis. RESULTS: Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001). CONCLUSIONS: In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.

Adult↗

PubMed2005

Comparison of hepatitis C virus NS5b and 5' noncoding gene sequencing methods in a multicenter study.

A national evaluation study was performed in 11 specialized laboratories with the objective of assessing their capacities to genotype hepatitis C virus (HCV) and define the applicability of a given genotyping method. The panel consisted of 14 samples positive for HCV RNA of different genotypes (including 3 samples with two different artificially mixed genotypes) and 1 HCV-negative sample. Seventeen sets of data were gathered from the 11 participating laboratories. The sensitivities ranged from 64.3 to 100% and from 42.7 to 85.7% for the methods that used sequencing of the NS5b region and the 5' noncoding (5' NC) region, respectively. When the data for the artificially mixed samples were excluded, NS5b genotyping gave correct results for 80% of the samples, 1.7% of the samples were misclassified, and 18.3% of the samples had false-negative results. By 5' NC-region genotyping methods, 58.3% of the results were correct, 29.7% were incomplete, 8.3% were misclassifications, 1.2% were false positive, and 2.4% were false negative. Only two procedures based on NS5b sequencing correctly identified one of the three samples with mixtures of genotypes; the other methods identified the genotype corresponding to the strain with the highest viral load in the sample. Our results suggest that HCV 5' NC-region genotyping methods give sufficient information for clinical purposes, in which the determination of the subtype is not essential, and that NS5b genotyping methods are more reliable for subtype determination, which is required in epidemiological studies.

5' Untranslated Regions↗

PubMed2004

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.

Adult↗

PubMed2004

Pegylated interferon alpha 2b and ribavirin in HIV/hepatitis C virus-co-infected non-responders and relapsers to IFN-based therapy.

BACKGROUND: Pegylated interferon alpha (PEG-IFN-alpha) and ribavirin is the most effective available treatment for chronic hepatitis C virus (HCV) infection. Its role in HIV/HCV-co-infected patients who have failed IFN-based therapy is unclear. OBJECTIVE: The aim of this study was to determine the safety and efficacy of this therapy in HIV/HCV-co-infected non-responders and relapsers. DESIGN: An open-label cohort study of 32 non-responders and relapsers to IFN (with or without ribavirin). Patients were treated for 48 weeks with PEG-IFN-alpha 2b and ribavirin. MAIN OUTCOME MEASURE: A sustained virological response (SVR) defined as a negative HCV-RNA level 24 weeks after the end of treatment. RESULTS: The mean age of the patients was 40 years; 78% were men, 67% had genotype 1, and 36% had bridging fibrosis or cirrhosis. The majority had a CD4 cell count greater than 200 cells/microl (97%) and an undetectable HIV-RNA level (81%). Fifteen patients (47%) withdrew because of adverse events, predominantly neuropsychiatric. In an intention-to-treat analysis, a SVR was observed in five patients (16%); 9% with genotype 1 versus 29% with genotype 3 and 33% with genotype 4 (P = NS). Additional, but statistically non-significant, univariate predictors of response were lower serum HCV-RNA (P = 0.07) and higher alanine aminotransferase levels (P = 0.055) at baseline. No patient with bridging fibrosis or cirrhosis responded. Treatment had a minimal impact on HIV parameters. CONCLUSION: PEG-IFN-alpha 2b and ribavirin is a potentially useful therapy in HIV/HCV-co-infected patients who have failed standard IFN-based regimens. Strategies to improve adherence are vital so as to maximize long-term response rates.

Adult↗

PubMed2004

Decreased frequencies of virus-specific T helper type 1 cells during interferon alpha plus ribavirin treatment in HIV-hepatitis C virus co-infection.

Anti-hepatitis C virus (HCV) treatment combining IFN-alpha and ribavirin (IFN+R) has still poorly defined effects on immune responses. Frequencies of T helper (Th) type 1 cells specific for HCV, cytomegalovirus (CMV) and HIV were measured in chronically HCV-infected patients with or without HIV co-infection during IFN+R treatment. Although scarce, peripheral blood HCV-specific Th1 cells did not change significantly, while frequencies of HIV and CMV-specific Th1 cells decreased in co-infected patients independently of CD4 cell count changes. This suggests that IFN+R therapy might compromise virus-specific immune defenses in immunosuppressed patients.

Antiviral Agents↗

PubMed2004

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection.

OBJECTIVE: The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liver-infiltrating monoclonal B cells in patients with HCV infection. METHODS: One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis. RESULTS: A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV- infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P = 0.004) and had longer duration of HCV infection (P = 0.009), higher serum cryoglobulin levels (P = 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P = 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed. CONCLUSION: Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.

Adult↗

PubMed2004

TaqMan amplification system with an internal positive control for HCV RNA quantitation.

BACKGROUND: Quantitation of hepatitis C virus (HCV) RNA has become an essential tool for monitoring antiviral therapies in chronically infected patients. Different quantitative HCV RNA assays have been reported, mainly using techniques based on signal amplification with branched DNA (bDNA) technology or target sequence amplification by reverse-transcription PCR method (RT-PCR). OBJECTIVES AND STUDY DESIGN: An RT-PCR assay using TaqMan (fluorescence-based real-time PCR) and minor groove binding (MGB) probes was designed for the quantitative determination of HCV RNA in the clinical samples. Calculation of the concentration of HCV RNA was based on an external standard curve in the presence of an internal positive control (IPC). RESULTS: The assay detected 550 international units (IU)/mL with >95% probability of a positive result, with a linear range extending up to 10,000,000 IU/mL. The test exhibited good reproducibility with intra-assay and inter-assay coefficients of variation (CV) of 1.6% and 3.2%, respectively. All the major HCV genotypes were quantified with equivalent efficiency and accuracy. HCV genotypes 5 and 6 have also been amplified but too few samples have been tested. The performance of this new assay for quantitation of HCV viremia was evaluated with 213 anti-HCV positive sera, 120 of which corresponded to 30 patients sampled during the therapy. We used the Amplicor HCV Monitor assay (Roche Diagnostics, France) and the bDNA VERSANT HCV RNA assay (Bayer Diagnostics, France) to analyze 173 and 40 samples, respectively. The assay described here was significantly correlated with both commercial assays (R2 = 0.9535, P < 0.0001 and R2 = 0.8508, P < 0.0001, respectively). CONCLUSION: The present study illustrated the high reproducibility and reliability of our TaqMan HCV assay. Moreover, the monitoring of viral decline with our assay gave the same results as those obtained with the commercial assays indicating that this new technique provides an attractive approach for measuring HCV viral load.

Genotype↗