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D Dhumeaux

Publications and source records attributed to D Dhumeaux.

At least 19 recordsLinked to original sources
PubMed2006

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b.

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.

Adult↗
PubMed2004

Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections.

This study reports evidence that hepatocellular steatosis, a frequent histological feature of chronic hepatitis C, is principally metabolic in hepatitis C virus (HCV) genotype 1-infected patients, whereas it is principally virus-induced in HCV genotype 3-infected patients. Multivariate analysis of data on 176 patients with chronic hepatitis C revealed that the severity of steatosis was independently related to HCV RNA load alone in patients infected by HCV genotype 3, whereas it was independently related to the body mass index, daily alcohol intake and histological activity grade (but not viral load) in patients infected by HCV genotype 1. These findings suggest that steatosis is a cytopathic lesion induced by HCV genotype 3, whereas HCV genotype 1 is not steatogenic per se or at the usual in vivo expression levels.

Adult↗
PubMed2004

Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis.

BACKGROUND AND AIM: Recent studies suggest that liver steatosis in chronic hepatitis C may be the expression of a direct cytopathic effect of hepatitis C virus (HCV), particularly in patients infected with genotype 3. To investigate this hypothesis, we studied the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies. METHODS: A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were selected according to the following criteria: presence of steatosis at initial biopsy; no antiviral treatment prior to the first biopsy; antiviral treatment received between the two biopsies; body mass index (BMI) <28 kg/m(2); absence of excessive alcohol intake; no serum hepatitis B surface antigen or human immunodeficiency virus antibodies; and absence of diabetes mellitus. Evolution of steatosis was examined by comparing steatosis grades between the two biopsies. RESULTS: Twenty five patients (16.5%) were sustained virological responders (SVR) to antiviral treatment. Steatosis evolution after antiviral treatment was as follows: improvement in 36% of cases; stability in 51%; and worsening in 13%. Steatosis improvement was significantly more frequent in SVR than in non-responders (NR) (64% v 31%; p<0.004). This significant difference occurred in patients infected with genotype 3 (91% v 19%; p<0.0001) but not in those infected with non-3 genotypes (43% v 34%; NS). Among the 25 SVR, improvement in steatosis was significantly more frequent in patients infected with genotype 3 than in those infected with non-3 genotypes (91% v 43%; p<0.04) whereas in NR, improvement in steatosis did not differ between those infected with genotype 3 and non-3 genotypes (19% v 34%; NS). In multivariate analysis, four factors were independently associated with steatosis improvement: sustained virological response to antiviral therapy (odds ratio (OR) 6.06 (95% confidence interval (CI) 1.61-22.9); p = 0.01), severe steatosis (OR 5.50 (95% CI 1.54-19.6); p = 0.01), HCV genotype 3 (OR 2.90 (95% CI 0.85-10.0); p = 0.07), and BMI >25 kg/m(2) (OR 0.24 (95% CI 0.08-0.73); p = 0.02). CONCLUSIONS: Our results showed significant improvement in steatosis in patients infected with HCV genotype 3, who achieved sustained viral clearance. This provides further evidence for direct involvement of HCV genotype 3 in the pathogenesis of hepatic steatosis.

Adult↗
PubMed2003

Impact of moderate alcohol consumption on histological activity and fibrosis in patients with chronic hepatitis C, and specific influence of steatosis: a prospective study.

AIM: To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C. METHODS: Daily alcohol intake (none, 1-20, 21-30, 31-50 g/day) and histological activity and fibrosis were recorded in 260 patients with chronic hepatitis C. RESULTS: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 53.8% in abstinent patients to 86.5% for an intake between 31 and 50 g/day (P = 0.003). In multivariate analysis, age > 40 years, alcohol intake between 31 and 50 g/day and moderate or severe steatosis were independently related to histological activity. The proportion of patients with moderate (F2) or marked (F3) fibrosis or cirrhosis (F4) gradually increased from 29.0% in abstinent patients to 67.6% for an intake between 31 and 50 g/day (P < 0.001). Multivariate analysis also showed that alcohol intake between 31 and 50 g/day, moderate or severe steatosis and histological activity were independently related to fibrosis. The deleterious effect of alcohol intake on histological lesions differed according to gender. CONCLUSIONS: This study demonstrates that both activity and fibrosis gradually increase according to the amount of alcohol ingested, and that even moderate alcohol consumption, as low as 31-50 g/day in men and 21-50 g/day in women, may aggravate histological lesions in patients with chronic hepatitis C.

Adult↗
PubMed2003

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗
PubMed2003

Impact of smoking on histological liver lesions in chronic hepatitis C.

AIMS AND METHODS: To examine the association between smoking and histological liver lesions in chronic hepatitis C, we studied 244 consecutive patients (152 men, 92 women; mean age 45.9 (12.6) years) with histologically proven chronic hepatitis C. Daily tobacco consumption during the six months preceding liver biopsy was recorded as the number of cigarettes smoked daily. Total lifetime tobacco consumption was recorded as the number of cigarette packs smoked per year (packs-years). Liver biopsy specimens were graded for histological activity and fibrosis according to the METAVIR scoring system. RESULTS: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 62.0% in non-smokers to 81.7% in patients who smoked more than 15 cigarettes per day (p<0.009). A similar relationship was observed with total lifetime tobacco consumption: 59.0% of patients who had never smoked had grade A2 or A3 disease activity compared with 84.6% of patients who smoked more than 20 packs per year (p<0.002). Multivariate analysis showed that age over 50 years (odds ratio (OR) 5.4), alcohol intake exceeding 20 g/day (OR 2.75), and tobacco consumption of more than 15 cigarettes/day (OR 3.6) were independently related to the histological activity score. No relationship was found between the severity of fibrosis and either daily tobacco consumption or total lifetime tobacco consumption. Multivariate analysis showed that only age over 50 years (OR 8.8), daily alcohol intake exceeding 30 g/day (OR 3.4), and histological activity score (OR 7.9) were independently related to the fibrosis score. CONCLUSION: This study suggests that smoking, independent of alcohol, could aggravate the histological activity of chronic hepatitis C and that patients with chronic hepatitis C virus infection should be advised to reduce or stop smoking.

Adult↗
PubMed2003

Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies.

BACKGROUND AND AIMS: Steatosis, a frequent histological finding in patients with chronic hepatitis C (CHC), has been suggested to influence liver fibrosis progression. The aim of the present study was to evaluate in patients with CHC and paired liver biopsies the relationship between the evolution of steatosis and that of fibrosis between the two biopsies. METHODS: Ninety six patients were selected according to the following criteria: absence of treatment; absence of cirrhosis at initial biopsy; and serum hepatitis B surface antigen and human immunodeficiency virus antibody negativity. Degrees of necroinflammatory activity, fibrosis, and steatosis grades were assessed in the two biopsies. In addition to histological lesions, parameters studied included the source of infection, duration of infection, body mass index, alcohol intake, alanine aminotransferase levels, hepatitis C virus genotype, and viral load. RESULTS: The mean interval between the two biopsies was 48 (32) months. Steatosis was found in 54% of patients at first biopsy, and was severe in 9%. Worsening of steatosis was observed in 34% of patients, stability in 50%, and improvement in 16%. Worsening of steatosis was significantly associated with hepatic fibrosis progression in patients with (p=0.03) or without (p<0.03) steatosis at diagnosis. Overall, fibrosis progression was observed in 31% of patients and stability in 69%. In a univariate analysis, fibrosis progression was associated with male sex (p=0.05), worsening of histological activity (p=0.04), and worsening of steatosis (p=0.0003). In a multivariate analysis, the only factor independently associated with fibrosis progression was worsening of steatosis (worsening v improvement/stability: odds ratio 4.7 (95% confidence interval 1.3-10.8); p=0.0001). CONCLUSIONS: Our results suggest that in untreated patients with CHC and serial liver biopsies, fibrosis progression is strongly associated with worsening of steatosis.

Adult↗
PubMed2002

Focal nodular hyperplasia of the liver in men: is presentation the same in men and women?

BACKGROUND: Focal nodular hyperplasia (FNH) of the liver is a benign hepatic lesion relatively common in women. No studies specifically designed to describe the presentation and imaging findings in males have been published. AIMS: The aims of this study were: (a) to describe the clinical and imaging findings in 18 men with FNH, and (b) to compare these data with those observed in 216 women with FNH observed during the same nine year period. PATIENTS AND METHODS: According to a final diagnosis of FNH assessed either by pathological examination or by magnetic resonance (MR), the medical charts of 18 men with FNH observed at our institution were reviewed. In order to compare clinical and MR presentations, the files of 216 women with a total of 291 FNH lesions, investigated during the same nine year period, were reviewed. RESULTS: Eighteen FNH lesions, with a mean diameter of 37.5 mm, were demonstrated in the 18 male patients. A total of 291 lesions with a mean diameter of 63.4 mm were comparatively demonstrated in 216 female patients. Mean age at diagnosis was significantly higher in men (p<0.01) and mean FNH size was significantly smaller in men (p<0.001). Surgery was more frequently performed in men (72.2%) than in women (16.7%) (p<0.001). CONCLUSIONS: Our data indicate that FNH is rare in men and that the lesions are smaller and more often atypical than those in women.

Abdominal Pain↗
PubMed2000

Oral contraceptive use and focal nodular hyperplasia of the liver.

BACKGROUND & AIMS: Because most patients with focal nodular hyperplasia (FNH) are young women, an important decision is whether to discontinue oral contraceptive (OC) use. The aims of this study were to evaluate (1) the number and size of FNH lesions in women with various patterns of OC use and in women without OC use and (2) the modifications in the number and size of FNH lesions during follow-up, according to OC use. METHODS: In a 9-year study in 216 women with FNH, the diameter and number of lesions documented by magnetic resonance (MR) imaging were evaluated (1) at diagnosis according to OC use as follows: group A, no OC use (n = 28); group B, high-dose OC use (n = 46); group C, low-dose OC use (n = 98); group D, successive use of high-dose and low-dose OCs (n = 33); and group E, use of progestogens only (n = 11); and (2) during follow-up in 136 women, 14 of whom were OC nonusers who stayed off OCs, 89 discontinued OC use, 26 took low-dose OCs, and 7 stayed on a progestogen only. Twelve women became pregnant. In 168 women, the diagnosis of FNH was made based on a combination of rigorously defined MR criteria. In the remaining 48 patients, diagnosis was by surgical biopsy (n = 36) or resection (n = 12). Mean diameter and number of lesion(s) per patient were assessed by MR imaging using the same protocol in all study patients. RESULTS: No significant differences in the number or size of lesions were found in the 5 patient groups. During follow-up, a change in lesion diameter occurred in only 4 women; this event was not influenced by OC use. In the 12 patients who became pregnant, lesion size was unchanged after delivery, pregnancy was uneventful, and delivery occurred spontaneously. CONCLUSIONS: These data suggest that (1) neither the size nor the number of FNH lesions are influenced by OC use; (2) size changes during follow-up are rare and do not seem to depend on OC use; and (3) pregnancy is not associated with FNH changes or complications.

Adolescent↗
PubMed2000

Routine detection and quantification of hepatitis B virus DNA in clinical laboratories: performance of three commercial assays.

The detection and quantification of hepatitis B virus (HBV) genomes in molecular biology-based assays appear to be the most reliable methods for monitoring HBV infection and assessing responses to antiviral treatment. The aim of this study was to evaluate the performance of three HBV-DNA detection and quantification assays currently used for the management of HBV-infected patients: a solution-hybridization assay based on hybrid-capture (Digene Hybrid-Capture, Murex Diagnostics, Dartford, UK); a signal-amplification assay based on 'branched-DNA' (bDNA) technology (Quantiplex HBV DNA, Bayer Diagnostics, Emeryville, CA); and a target-amplification assay based on competitive polymerase chain reaction (Amplicor HBV Monitor, Roche Molecular Systems, Pleasanton, CA). The Monitor assay was significantly more sensitive than both the hybrid-capture and bDNA methods. This better sensitivity appeared to be clinically relevant. The linear ranges of quantification in the hybrid-capture, bDNA and Monitor methods were 6.5-9 log10 genome copies/ml, 6.5-9.5 log10 genome equivalents/ml, and 3-5.5 log10 genome copies/ml, respectively. However, the HBV-DNA units used in the three assays were not comparable. The specificity of the hybrid-capture, bDNA and Monitor assays was 99.2% (95% confidence interval: 97.7-100.0%), 99.2% (97.7-100.0%), and 97.8% (95.3-100%), respectively. Their within-run coefficients of variation and log10 SDs were 5.5% (+/- 0.025 log10 copies/ml), 6.7% (+/- 0.029 log10 Eq/ml) and 21.0% (+/- 0.093 log10 copies/ml), respectively. Between-run coefficients of variation ranged from 4.4-39.1%, 5-39.5%, and 17.8-96.1%, respectively. The competitive PCR-based Monitor assay appears to be significantly more sensitive but slightly less specific and reproducible than the hybrid-capture and bDNA methods. Given their respective performance, these three assays should be used in complementary fashion in the management of HBV-infected patients.

DNA, Viral↗