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Biomedical subjects

Yves Benhamou

Publications and source records attributed to Yves Benhamou.

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

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

Anti-hepatitis B virus efficacy of tenofovir disoproxil fumarate in HIV-infected patients.

Tenofovir disoproxil fumarate (TDF) has shown in vitro activity against both HIV and hepatitis B virus (HBV). We retrospectively evaluated the efficacy of TDF (300 mg/d), administered as a part of anti-retroviral therapy, in a large cohort of HIV/HBV-coinfected patients. Sixty-five HIV/HBV-coinfected patients who received TDF for at least 6 months with serum HBV DNA levels above 2.3 log10 copies/mL at TDF initiation and who had stored serum samples before and during TDF therapy were included. Serum HBV DNA was measured on stored samples. The median follow-up period was 12 (Q1-Q3: 8-17) months. Serum hepatitis B e antigen (HBeAg) was positive in 54 patients (83.1%). Fifty-two patients (80.0%) were receiving lamivudine (LAM) (150 mg twice a day), and 68.8% had documented LAM resistance at baseline. Among HBeAg-positive patients, the median reduction from baseline (8.17; Q1-Q3 = 7.30-8.30 log10 copies/mL) of serum HBV DNA was 4.56 log10 copies/mL (Q1-Q3 = 3.33-5.55) (P < .0001). In HBeAg-negative patients, serum HBV DNA decline from baseline (4.83; Q1-Q3 = 2.69-6.40 log10 copies/mL) was 2.53 log10 copies/mL (Q1-Q3 = 0.39-4.10). At the end of the study, HBV DNA became undetectable in 29.6% and 81.6% of the HBeAg-positive and HBeAg-negative patients, respectively. Serum HBeAg became negative in 4 patients, 2 of whom acquired serum hepatitis B e antibody. In conclusion, this retrospective analysis demonstrates the efficacy of TDF against wild-type, presumed precore mutants and LAM-resistant HBV when used as a part of anti-retroviral therapy in HIV-coinfected patients.

Adenine↗
PubMed2006

Efficacy of infliximab in Crohn's disease. Results of a retrospective multicenter study with a 15-month follow-up.

OBJECTIVES: To evaluate prescription practices and response to infliximab treatment for Crohn's disease (CD). PATIENTS AND METHODS: The files of CD patients treated with at least one infusion of infliximab treated in gastroenterology units belonging to university teaching hospitals of the Parisian hospitals group (Assistance Publique-Hôpitaux de Paris (AP-HP) during the year 2000 were analyzed retrospectively. RESULTS: One hundred and thirty-seven patients (36.0 +/- 12.7 years, 92 females) from 12 centers were studied. Indication for treatment was fistulae or perianal disease in 39% of patients, active Crohn's disease in 45% and mixed conditions in 16%. Mean follow-up was 15.2 +/- 7.2 months. The overall response rate was 85%. No predictive factor of sustained remission could be identified. The mean time to relapse was to 3.9 +/- 3.1 months. Thirty-eight patients were on maintenance therapy at the end of the follow up; 37% exhibiting progressive lost of response to treatment. Immunosuppressive therapy was added to infliximab in 78% of cases but response to infliximab was not modified by addition of immunosuppressive drugs. Adverse events, most frequently minor, were noted in 23% of the patients. CONCLUSION: This retrospective study confirms the efficacy and safety of infliximab in CD.

Adult↗
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↗
PubMed2006

Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor BILN 2061.

We analysed viral kinetics from a 2-day treatment with BILN 2061, a serine protease inhibitor of hepatitis C virus, in patients chronically infected with genotype 1 hepatitis C virus. The efficiency (E), describing inhibition of viral production, was above 99.45% in all patients with minor or moderate fibrosis receiving doses of 200mg and 500 mg twice daily and larger than in previous studies for interferon-based treatments. However, epsilon was slightly smaller in patients with cirrhosis given 200mg and markedly smaller in patients given 25 mg. Estimates of viral clearance and infected-cell loss support conclusions on these rates and on treatment mechanisms from previous studies on interferon-alpha-based treatments.

Adult↗
PubMed2005

Therapeutic management of hepatitis and HIV infection in co-infected patients: results of a survey performed before the 2005 Consensus Conference.

The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of 24 European countries showed that access to anti-HCV treatment is low (approximately 10%) in patients with HCV/HIV co-infection--generally access is higher in Western Europe than in Eastern or Northern Europe. This low use of anti-HCV therapy is not a result of poor availability (of drugs or virological tests), which are available in all countries surveyed. Recently published trials in co-infected patients and the outcome from this Consensus Conference will hopefully lead to wider access to anti-HCV therapy and better management of co-infected patients across Europe.

Antiviral Agents↗
PubMed2005

Treatment algorithm for chronic hepatitis B in HIV-infected patients.

Recommendations for the treatment of chronic hepatitis B (CHB) in HIV-infected patients is complex due to the lack of controlled trials and the dual activity of therapeutic agents on both viruses. Thus, proposals for optimal anti-HBV therapy in HIV-infected patients should be pragmatic using the knowledge from HBV mono- and HIV/HBV co-infected studies. There are four approved drugs for the treatment of CHB which include interferon alpha (IFN), lamivudine (LAM), entecavir (ETV) and adefovir dipivoxil (ADV). LAM, tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are approved for HIV and active against HBV. Studies with IFN are limited in HIV/HBV co-infected patients but suggest a decreased response compared with HBV mono-infected patients. LAM and FTC are effective against HBV but are associated with a high rate of HBV resistance. ETV, ADV and TDF are effective against wild-type and LAM-resistant HBV with a favourable resistance profile shown for ADV and TDF. Interferon, ADV or ETV are the preferable drugs in HBV naive patients who do not require HIV therapy. Combination of TDF plus FTC or LAM should be proposed in patients with therapeutic indication for both viruses. TDF should be included in the anti-retroviral regiment of patients with HBV resistance to lamivudine.

Algorithms↗
PubMed2005

Natural history and predictors of disease severity in chronic hepatitis C.

Cirrhosis is the end-stage consequence of fibrosis progression in patients with chronic hepatitis C. The median time from infection to cirrhosis is 30 years, with a high inter-individual variability, which is now better understood. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male gender, alcohol consumption, HIV co-infection and low CD4 count. Metabolic conditions such as steatosis, being overweight and diabetes are emerging as independent co-factors of fibrogenesis. The recent validation of non-invasive biomarkers should facilitate the study of fibrosis progression in large populations.

Disease Progression↗
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

Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C.

BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1 in three 2-day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection. The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected with non-genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2), double-blind pilot study. HCV-RNA levels decreased by > or =1 log(10) copies/mL in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of <1 log(10) copies/mL. Three of 8 treated patients showed no response. There was no correlation between baseline viral concentration or genotype and response. BILN-2061 exhibited good systemic exposure after oral administration and was well tolerated. In conclusion, the antiviral efficacy of the HCV serine protease inhibitor BILN-2061 is less pronounced and more variable in patients with HCV genotype 2 or 3 infection compared with previous results in patients with HCV genotype 1. A lower affinity of BILN-2061 for the NS3 protease of genotypes 2 and 3 HCV is most likely a major contributor to these findings.

Administration, Oral↗
PubMed2005

HIV-1/hepatitis B coinfection.

Reviews the epidemiology, natural history and the current status of treatment of HIV/hepatitis B coinfection.

Anti-HIV Agents↗