Biomedical subjects

C Trepo

Publications and source records attributed to C Trepo.

At least 19 recordsLinked to original sources

PubMed2006

Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin in patients with recurrent hepatitis C virus infection posttransplantation.

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Adult↗

PubMed2006

Screening campaign of hepatitis C among underprivileged people consulting in health centres of Lyon area, France.

BACKGROUND: A screening campaign for hepatitis C virus (HCV) infection was carried out in eight health centres of Lyon from June 2003 until March 2004. The population targeted for screening was underprivileged individuals without any social insurance, protected by Couverture Mutuelle Universelle or Aide Médicale Etat (AME), to estimate the prevalence of anti-HCV antibodies in this population and to identify associated risk factors. METHODS: After training in HCV infection and screening, 43 general practitioners participated in the campaign. Information about patient socio-demographics and risk factors was collected prior to proposing screening serology. Blood samples were often taken in health centres. Follow-up of positive cases was organised via the Reference Centre of HCV Infection in Lyon with possible specialised consultations in health centres. RESULTS: The average age of the 988 individuals in the campaign was 37 years; 51% were women; 54% had a foreign nationality; 21% lived in sheltered accommodation; 19% were lodged in third-party accommodation; 9% were homeless; and 57% possessed less than euro562 (Revenu Minimum d'Insertion level). Screening was not proposed to nine patients because of medico-psychological problems. The acceptance rate for screening was 98.8% (967/979), and testing was carried out on 97.6% of these subjects (944/967). The prevalence of anti-HCV antibodies in the sample was 4.7% (44/944) (95% CI = 3.4-6.2). Nearly 80% of positive cases were unknown prior to the campaign. Multivariate logistic regression modelling identified lifetime injection drug use [odds ratios (OR) = 15.99; P < 0.0001], lifetime medical care in a foreign country (OR = 4.46; P = 0.001), and wearing tattoos (OR = 2.75; P = 0.048) as significant risk factors for carrying anti-HCV antibodies. Characteristics independently associated with HCV seropositivity were age between 40 and 49 years, AME benefits, and no social insurance. CONCLUSION: Wide acceptance of screening, high prevalence of anti-HCV antibodies (much higher than in the French population in general), a high proportion of positive cases unknown beforehand, and satisfactory follow-up of seropositive patients are all factors which support the need for a screening campaign targeting HCV infection in underprivileged persons living in France.

Adolescent↗

PubMed2006

Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients.

We describe 3 symptomatic cases of neurologic syphilis that occurred after the administration of the usual therapy for primary or secondary syphilis in human immunodeficiency virus (HIV)-infected patients. We discuss the difficulty of diagnosing neurosyphilis, the need for lumbar puncture, and risk factors of relapse. Because HIV infection may alter the natural history and response of neurologic syphilis to treatment, scrupulous follow-up and repeated cycles of therapy are warranted.

Adult↗

PubMed2006

Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus.

OBJECTIVE: The treatment of the rheumatological manifestations associated with hepatitis C virus (HCV) remains difficult. To examine the safety of anti-tumour necrosis factor-alpha treatment, nine patients having rheumatological manifestations associated with HCV were treated with etanercept 25 mg twice a week for 3 months. METHODS: Five patients had a positive viral load at study entry (Group I), four were negative (Group II). Clinical data recorded were: disease duration, painful and swollen joint count, patient global and physician global assessment, the number of 18 specified fibromyalgia tender points and the Health Assessment Questionnaire score. Laboratory studies included checking for the presence of cryoglobulinaemia and transaminase levels. Quantitative HCV viral RNA was performed by real-time polymerase chain reaction (PCR). RESULTS: At 3 months, no patient was found to have evidence of increased hepatic inflammation based on serial serum transaminase levels. In the five patients from Group I with detectable HCV RNA, no significant viral load increase was observed. No reactivation was observed in the four patients from Group II with undetectable HCV RNA. The effect on the clinical rheumatological manifestations was more heterogeneous but appears to be lower than that observed in rheumatoid arthritis. CONCLUSION: In this phase II open short-term study, etanercept appeared to be safe in patients with articular manifestations associated with HCV.

Antirheumatic Agents↗

PubMed2006

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine.

Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a 2-year period. We evaluated 283 lamivudine-naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load, at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period.

Adolescent↗

PubMed2006

A recent increase in AIDS at Lyon University Hospitals: patient characteristics and comparisons with previous years.

BACKGROUND: A 36% increase in the incidence of AIDS was observed in 2002/2003 compared with 2000/2001 at Lyon University Hospitals. OBJECTIVES: We compared the characteristics of these patients with the characteristics of those diagnosed previously with AIDS. METHODS: Data for all patients with AIDS diagnosed at Lyon University Hospitals were analyzed. The data were collected prospectively. Multiple logistic regression was used for analysis. RESULTS: The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1985-1989 period were: homosexual exposure [odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.8]; heterosexual exposure in an endemic area (OR 22.5; 95% CI 6.8-74.8), compared with other exposure to HIV; lymphoma as initial AIDS event (OR 10.3; 95% CI 2.7-39.1) compared with Pneumocystis carinii pneumonia; and age at first AIDS event aged 34-38 years (OR 2.5; 95% CI 1.0-6.4), aged 39-46 years (OR 5.1; 95% CI 2.2-11.8), and aged 47-84 years (OR 10.6; 95% CI 4.5-25.1) compared with aged <30 years. The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1997/2001 period were age at first AIDS event aged 34-38 years (OR 0.4; 95% CI 0.2-0.9) compared with aged <30 years. CONCLUSION: Recently diagnosed AIDS patients differed from those diagnosed previously, showing an epidemic switch in different populations. The characteristics of the AIDS population in 2002/2003 might reflect public health messages disseminated around 10 years ago or more for the prevention of HIV transmission. Anticipation of populations affected by the AIDS epidemic is difficult.

Acquired Immunodeficiency Syndrome↗

PubMed2006

In vitro characterization of the anti-hepatitis B virus activity and cross-resistance profile of 2',3'-dideoxy-3'-fluoroguanosine.

The fluorinated guanosine analog 2',3'-dideoxy-3'-fluoroguanosine (FLG) was shown to inhibit wild-type (wt) hepatitis B virus (HBV) replication in a human hepatoma cell line permanently expressing HBV. Experiments performed in the duck model of HBV infection also showed its in vivo antiviral activity. In this study, we investigated the mechanism of inhibition of FLG on HBV replication and its profile of antiviral activity against different HBV or duck hepatitis B virus (DHBV) drug-resistant mutants. We found that FLG-triphosphate inhibits weakly the priming of the reverse transcription compared to adefovir-diphosphate in a cell-free system assay allowing the expression of an enzymatically active DHBV reverse transcriptase. It inhibits more potently wt DHBV minus-strand DNA synthesis compared to lamivudine-triphosphate and shows a similar activity compared to adefovir-diphosphate. FLG-triphosphate was most likely a competitive inhibitor of dGTP incorporation and a DNA chain terminator. In Huh7 cells transiently transfected with different HBV constructs, FLG inhibited similarly the replication of wt, lamivudine-resistant, adefovir-resistant, and lamivudine-plus-adefovir-resistant HBV mutants. These results were consistent with those obtained in the DHBV polymerase assay using the same drug-resistant polymerase mutants. In conclusion, our data provide new insights in the mechanism of action of FLG-triphosphate on HBV replication and demonstrate its inhibitory activity on drug-resistant mutant reverse transcriptases in vitro. Furthermore, our results provide the rationale for further clinical evaluation of FLG in the treatment of drug-resistant virus infection and in the setting of combination therapy to prevent or delay drug resistance.

Adenine↗

PubMed2005

[Tolerance and efficacy of conformal radiotherapy for hepatocellular carcinoma in cirrhotic patients. Results of the French RTF1 phase II trial].

PURPOSE: While some patients presenting with hepatocellular carcinoma (HCC) benefit from curative therapies (transplantation, surgery, percutaneous ablation), others are only candidates for palliative options such as chemoembolization or symptomatic care. Although conventional external-beam radiotherapy of the liver is regarded as little efficient and potentially toxic in cirrhotic patients, 3-dimensional conformal radiotherapy (CRT), by decreasing the amount of normal liver included in the radiation portal, allows dose escalation to occur without increasing the risk of radiation-induced hepatitis. This trial was designed to assess the efficacy and tolerance of CRT for small-size HCC in cirrhotic patients. PATIENTS AND METHODS: Prospective phase II trial including stage A/B cirrhotic patients with small-size HCC not suitable for curative treatments; CRT consisted in a standard fractionation radiation, with a total dose of 66 Gy. RESULTS: Twenty-seven patients were included, 15 of whom had previously been treated for HCC; mean age was 68. Among the 23 assessable patients, 18 (78%) presented with complete response, 3 (13%) with partial response, and 2 with no response. Acute complications occurred in 24 patients, and were mainly acceptable (grade 1/2: 22 patients, grade 3/4: 11 patients, 4 (15%) of whom had clinical and/or hematological toxicities). Only 2 (9%) grade 3/4 clinical and/or hematological late toxicities are reported. CONCLUSION: CRT is a non-invasive curative technique highly suitable for small-size HCC in cirrhotic patients; further investigations are needed to compare it to the other available treatments, and to integrate it into the curative therapeutic algorithm of HCC.

Aged↗

PubMed2005

Prevalence and sexual risk of hepatitis C virus infection when human immunodeficiency virus was acquired through sexual intercourse among patients of the Lyon University Hospitals, France, 1992-2002.

To report the prevalence and the risk factors for hepatitis C virus (HCV) infection in a hospital cohort of 2691 sexually human immunodeficiency virus (HIV)-infected patients. The patients were enrolled in the Lyon section of the French Hospital Database on HIV between 1992 and 2002. Baseline characteristics were analysed. The detection of HCV-antibodies (Ab) was used for diagnosis. The HCV-Ab prevalence rate was 5.7 and 12.89% for individuals infected by HIV after homosexual intercourse or heterosexual intercourse, respectively. HCV-Ab was three times more frequently found among patients infected with HIV after heterosexual intercourse compared with patients infected with HIV after homosexual intercourse (adjusted OR: 3.2, 95% CI: 2.28-4.62, multiple logistic regression). The risk of HCV infection among HIV-infected individuals differed according to sexual behaviour. The determinants associated with HCV transmission through the sexual route needs to be explored further.

Adolescent↗

PubMed2005

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Adult↗

PubMed2004

Analysis of HCV co-infection with occult hepatitis B virus in patients undergoing IFN therapy.

BACKGROUND/AIM: Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in the absence of hepatitis B surface antigen (HBsAg) in the patient serum. Although such infections have been identified in patients with chronic hepatitis C, the clinical significance of those co-infections is still not understood. Our aim was, therefore, to assess the prevalence and clinical consequences of occult HBV infection in chronic hepatitis C patients undergoing antiviral therapy. METHODS: The study population consisted of 53 HBsAg-negative patients with chronic hepatitis C treated with IFN/ribavirin or IFN/ribavirin/amantadine. Nine patients experienced a viral breakthrough (BT), 30 were non-responders (NR) and 14 were responders (R). HBV-DNA detection by PCR was performed using primers specific for the S region of the HBV genome and HCV-RNA detection by PCR with primers localised in both the 5'NC and core region of HCV genome, before, during and after treatment. Viral genome sequences were also studied. RESULTS: Occult HBV genomes were found in the serum of four of 53 (7.5%) patients, unrelated to anti-HBc status. No significant differences in biochemical, virological, or histological markers, age, duration of infection, were observed in patients with or without HBV DNA. There was an inverse correlation in the evolution of HBV DNA and HCV RNA levels. Direct sequencing showed that S gene of occult HBV presented mutations in the "a" determinant while no specific mutation in the core region of HCV was observed. None of the four patients co-infected with HBV and HCV were responders to anti-HCV therapy. CONCLUSION: In our clinical setting, the prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection. Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy.

Adult↗

PubMed2004

Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy.

Little is known about hepatitis C virus (HCV) breakthrough during antiviral therapy, although it would help in understanding HCV resistance to current antiviral treatments. To analyse the implication of virological factors and the vigour of humoral immune responses in this phenomenon, we studied nine chronic hepatitis C patients with a viral breakthrough during IFN/ribavirin combination therapy, as well as five responders and five non-responders. The IRES and regions coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and during breakthrough, and after treatment. The major variant sequence was obtained by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in all patients and sequencing after cloning in seven genotype 1b-infected patients. Humoral responses against HCV epitopes were also analysed. The major sequences of IRES, PePHD, and NS5B remained stable during treatment, regardless of the treatment response. However, the capsid protein and the regions flanking PePHD showed sequence variations in breakthrough patients, although no specific mutation was identified. The variable V3 region of NS5A, but not the PKR-binding domain and the ISDR, seemed to be associated with differences in response to treatment. The analysis of HCV quasispecies revealed no characteristic pattern during treatment in breakthrough patients, whose HCV genome profiles looked most similar to that of non-responders. The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations.

Adult↗

PubMed2004

[Primary non-Hodgkin lymphoma of the liver in HIV infected patient: case-report].

INTRODUCTION: Primary liver non-Hodgkin's lymphoma, are extremely rare in HIV-infected patient. Most of them are diffuse large-cell lymphoma with B cell type. EXEGESIS: We report here the case of a 34-year-old HIV-infected patient, admitted for jaundice and fever since 15 days. Abdominal computerised tomography showed numerous hypodense lesions on all liver segments. The various biological, microbiological and morphological examinations (ultrasound, MRI with intravenous contrast agent specific for the liver) initially suggested a tumoral origin. The liver biopsy concluded to a large B-cell lymphoma. A chemotherapy (CHOP) with anti-CD20 monoclonal antibody (rituximab) was initiated without discontinuing antiretroviral therapy. CONCLUSION: This case-report does emphasize on the numerous presentations of primary liver lymphoma in HIV-Infected patient, and we illustrate the interest of MRI using a new intravenous contrast agent critical for differential diagnosis.

Adult↗

PubMed2004

Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND AND AIMS: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). METHODS: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level > or =1.2 times the upper limit of normal, and serum HBV DNA level > or =6 log(10) copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. RESULTS: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine group compared with -2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log(10) copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. CONCLUSIONS: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

Adenine↗

PubMed2004

The AIDS epidemic in Lyon: patient characteristics and defining illnesses between 1985 and 2000.

OBJECTIVES: To define the characteristics of 1899 patients diagnosed with AIDS at Lyon University Hospitals (LUH) across four time periods corresponding to different antiretroviral eras, and to analyse the evolution of specific AIDS-defining illnesses (ADIs) with time. METHODS: All AIDS patients at LUH between 1 January 1985 and 31 December 2000 were included in the study. The data were compared using the chi(2) test and one-way analysis of variance. RESULTS: The absolute number of new AIDS cases increased by 30.3% between 1985 and 1995 but decreased by 26.5% between 1996 and 2000. The proportion of women with AIDS increased significantly (P<0.001) and mean age at diagnosis also increased significantly over time (P<0.001). The proportion of infection through heterosexual contact increased dramatically, while that through homo/bisexual intercourse or injection drug use (IDU) decreased significantly (P<0.001). The absolute number of ADIs declined with the introduction of highly active antiretroviral therapies (HAART) (P<10(-6)). Pneumocystis carinii pneumonia remained the leading ADI in 1996-2000 (23.3%). A significant increase in the proportion of non-Hodgkin's lymphoma (NHL) was observed over time (P<10(-5)) but the number of new NHL cases decreased during HIV infection after 1996. CONCLUSIONS: The decline in the incidence of AIDS with the advent of HAART was confirmed in our hospital cohort. The gradual increase in the proportion of NHL among ADIs underscores the long latency period between infection with HIV and the achievement of an effect of HAART on HIV-associated lymphomagenesis.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Characteristics of patients diagnosed with AIDS shortly after first detection of HIV antibodies in Lyon University hospitals from 1985 to 2001.

A diagnosis of AIDS shortly after the detection of HIV antibodies suggests a long-lasting course of the disease without care. The factors associated with a short delay between the initial HIV-1-positive test and the first AIDS-defining event were identified in 1901 patients from 1985 to 2001 in Lyon University hospitals. A total of 576 individuals (30.3%) had an interval of </=3 months between the detection of HIV infection and AIDS. The factors independently associated with a delay of </=3 months were: age from 30 to 44 years [odds ratio (OR) 2.5; 95% confidence interval (CI) 1.9-3.2]; age from 45 to 59 years (OR 5.6; 95% CI 3.9-7.8); age >/=60 years (OR 4.5; 95% CI 2.5-8.1), compared to those<30 years old; heterosexuality (OR 2.4; 95% CI 1.6-3.4); injection drug use (OR 2.1; 95% CI 1.5-2.7); and other exposures (OR 2.4; 95% CI 1.6-3.4), compared to homosexual exposure; two opportunistic infections at AIDS (OR 1.8; 95% CI 1.4-2.4) compared to one; and Pneumocystis carinii pneumonia as initial AIDS event (OR 2.6; 95% CI 1.8-3.7), compared to Kaposi's sarcoma. These results provide opportunities to refocus local public health interventions to reduce delayed access to care.

AIDS Serodiagnosis↗

PubMed2004

Ultrasound detection of spontaneous hepato-cellular carcinomas in X/myc bitransgenic mice.

AIMS: To evaluate trans-abdominal ultrasound for the detection of Hepatocellular carcinoma (HCC) in a bitrasgenic murine (X/myc) model using a commercially available high-frequency ultrasound unit. METHODS: Sixty-one female animals were included in this study. These animals were submitted to a single ultrasound examination of the liver under general anesthesia (isoflurane), and then euthanized. Results of ultrasound were compared with necropsy and histopathology. RESULTS: The lesions demonstrated a fairly consistent aspect (oval- or round-shaped, well-defined hypoechoic homogeneous lesions), and lesions as small as 2 mm were identified. For detection of hepatic nodules per mouse the sensitivity was 75%, the specificity was 100% and the accuracy was 88.5%. For detection of hepatic focal lesions per lesions the overall sensitivity was 60%, the specificity was 97%, and the accuracy was 75.9%. Contrast-enhanced harmonic ultrasound imaging did not improve the identification of the lesions in our experimental conditions. CONCLUSION: High-frequency ultrasound appears to be an efficient tool allowing new possibilities to use this animal model and evaluate new therapies in longitudinal studies, which are much more powerful.

Animals↗

PubMed2004

Effect of a combination of clevudine and emtricitabine with adenovirus-mediated delivery of gamma interferon in the woodchuck model of hepatitis B virus infection.

Our aim was to evaluate the antiviral effect of a combination of two nucleoside reverse transcriptase inhibitors, emtricitabine (FTC) and clevudine (L-FMAU), with the addition of an adenovirus-driven delivery of recombinant gamma interferon (IFN-gamma) in the woodchuck model of hepatitis B virus infection. Six woodchuck hepatitis virus (WHV)-infected woodchucks received L-FMAU (10 mg/kg) plus FTC (30 mg/kg) intraperitoneally for 8 weeks; six other animals received in addition an intravenous injection of a recombinant adenovirus vector expressing woodchuck IFN-gamma (Ad-IFN) at weeks 4 and 8. In the control group, two animals received Ad-IFN alone, two received adenovirus vector expressing the green fluorescent protein reporter gene, and one remained untreated. In less than 2 weeks, all woodchucks that received L-FMAU plus FTC showed a rapid and marked inhibition of viral replication, with a 4-log(10) drop in serum WHV DNA. In two animals, viremia remained suppressed for several months after the end of treatment. Similarly, a dramatic decrease in intrahepatic replicative intermediates of viral DNA was observed in the L-FMAU/FTC-treated groups. The additional administration of Ad-IFN led to increased inflammation in the liver but did not enhance the antiviral effect of the L-FMAU/FTC combination. In conclusion, therapies combining L-FMAU and FTC in WHV-infected woodchucks resulted in a potent and sustained antihepadnaviral effect both in the liver and in the blood circulation. However, no extra benefit of adding IFN-gamma gene transduction to the L-FMAU/FTC combination could be detected.

Adenoviridae↗