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S Pol

Publications and source records attributed to S Pol.

At least 37 records · Page 2Linked to original sources
PubMed2002

Characterization of low- and very-low-density hepatitis C virus RNA-containing particles.

The presence of hepatitis C virus (HCV) RNA-containing particles in the low-density fractions of plasma has been associated with high infectivity. However, the nature of circulating HCV particles and their association with immunoglobulins or lipoproteins as well as the characterization of cell entry have all been subject to conflicting reports. For a better analysis of HCV RNA-containing particles, we quantified HCV RNA in the low-density fractions of plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated chronically HCV-infected patients. HCV RNA was always found in at least one of these fractions and represented 8 to 95% of the total plasma HCV RNA. Surprisingly, immunoglobulins G and M were also found in the low-density fractions and could be used to purify the HCV RNA-containing particles (lipo-viro-particles [LVP]). Purified LVP were rich in triglycerides; contained at least apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical particles with a diameter of more than 100 nm and with internal structures. Delipidation of these particles resulted in capsid-like structures recognized by anti-HCV core protein antibody. Purified LVP efficiently bind and enter hepatocyte cell lines, while serum or whole-density fractions do not. Binding of these particles was competed out by VLDL and LDL from noninfected donors and was blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the LDL receptor increased their internalization. These results suggest that the infectivity of LVP is mediated by endogenous proteins rather than by viral components providing a mechanism of escape from the humoral immune response.

Hepacivirus↗
PubMed2002

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.

Adult↗
PubMed2001

[Management of C virus infection in patients coinfected with HIV treated with antiretroviral agents].

CONTEXT: The prevalence of hepatitis C virus (HCV) infection in patients infected by the human immunodeficiency virus (HIV) varies from 10 to 30%, depending on the mode of contamination, and reaches about 80% in intravenous drug users and hemophiliacs. The two viral infections can be treated simultaneously or, on the contrary, one may be given priority depending on the respective pathological or viral situations. MANAGEMENT OF COINFECTIONS: HCV infection does not appear to affect the natural course of HIV infection. Inversely, HIV infection aggravates HCV infection by amplifying HCV replication. This leads to a risk of more severe liver disease and a more rapid progression to cirrhosis. Mortality in HIV-infected patients is higher. This points to the importance of early diagnosis and treatment aimed at avoiding progression to potentially severe liver disease. The impact of highly effective anti-HIV tritherapy regimens, particularly restoration of immune competence, and of drug-induced hepatitis on the natural history of HCV infection should be taken into consideration when making management decisions concerning implementation of antiretroviral or anti-hepatitis C treatments. PERSPECTIVES: The long-term efficacy of alpha-interferon given in a single-drug regimen has been mediocre. New perspectives have appeared with the development of new treatments, particularly the ribavirin-alpha-interferon combination or the development of delayed-release alpha-interferon.

Anti-HIV Agents↗
PubMed2001

Immunotherapy of chronic hepatitis B by anti HBV vaccine: from present to future.

Chronic liver disease and hepatocellular carcinoma associated with chronic hepatitis B virus (HBV)-infection are among the most serious human health problems in highly endemic regions. Current therapeutic approaches to control chronic hepatitis such as interferon-alpha and lamivudine are unsatisfactory. Vaccination would be the therapeutic procedure with the lowest cost and the potentially greatest benefit. The immunogenicity of selected HBV envelope- or capsid-based vaccine formulations for the induction or the broadening of T and B cell responses, deficient in HBV chronic carriers, are currently under study in animal models and in clinical trials.

Animals↗
PubMed2001

Efficacy and limitations of a specific immunotherapy in chronic hepatitis B.

BACKGROUND/AIMS: This controlled study aimed to evaluate the efficacy and potential side effects of hepatitis B virus (HBV) vaccination as active immunotherapy in HBV-related chronic hepatitis. METHODS: The 118 included patients were 'naive' subjects who had never received any previous anti-HBV therapy, showed detectable serum HBV DNA and had biopsy-proven chronic hepatitis. In a 12-month follow-up they were given either five intramuscular injections of 20 microg of a preS2/S (GenHevac B, Pasteur-Mérieux) (n = 46) or an S vaccine (Recombivax Merck & Co.) (n = 34) or no treatment as a control (n = 37). The efficacy of vaccination was evaluated by testing for serum HBV DNA negativation using a standard liquid hybridization assay. RESULTS: Three months after the first three vaccine injections, the percentage of serum HBV DNA negativation was higher in the vaccine groups (16.3%) than in the control group (2.7%) (P = 0.033, by the chi2 Pearson test) and was more frequently observed in patients who had pretreatment viremia >200 pg/ml (none in the control group vs. 16.7% in the vaccinated groups) (P = 0.025). After 12 months follow-up and five vaccine injections, there was no difference in the rate of serum HBV DNA negativation between vaccinated and unvaccinated subjects but HBV vaccines significantly decreased the HBV viral load between the sixth and twelfth months (P = 0.04) in contrast with the control group. The rate of HBe/anti-HBe seroconversion after 6 months of follow-up occurred only in eight (13.3%) vaccinated patients and in one (3.6%) of the controls. Disappearance of serum HBsAg was not observed in any of the patients. CONCLUSIONS: This controlled study offers direct evidence that the HBV vaccine may decrease HBV replication in chronic hepatitis B patients. It also emphasizes the need for reinforced immunization strategies as well as combination therapies.

Adult↗
PubMed2001

Hepatitis activity index is a key factor in determining the natural history of chronic hepatitis C.

To analyze the spontaneous pathologic progression of chronic hepatitis C, we analyzed the histopathologic semiquantitative scores (Metavir and Knodell) of sequential liver biopsies performed in untreated hepatitis C virus (HCV)-infected patients. Subjects included 35 men and 41 women, with a mean age of 41 +/- 12 years, a duration of HCV infection of 11 +/- 5 years, and an interval between liver biopsies of 3.7 +/- 2.5 years. Results obtained using the Knodell score and the Metavir score were similar. At the first biopsy, 78.9% of patients had a low activity score (A0-A1) and 82.9% had a low fibrosis score (F0-F2). At the second biopsy, the activity decreased in 9.2%, was unchanged in 72.4%, and increased in 18.5%. An increase in activity was more frequently observed in patients infected with genotype 1 (28.9%) than with others (7.7%; P =.04); the yearly progression of activity was significantly higher in patients with a low rather than high initial activity score (0.11 v -0.02; P <.01). An increase in fibrosis was noted in 13.3% of those with a low and 43.8% of those with a high initial activity score (P <.01), with a highest rate of yearly fibrosis progression (0.12 U). In multivariate analysis, only a high activity score was significantly associated with an increased risk of fibrosis progression (relative risk, 25.5; 95% confidence interval, 2.7 to 238; P =.004). Spontaneous chronic hepatitis C evolution is worsening in only 20% of patients. Fibrosis progression is significantly associated with the necroinflammatory activity suggesting that this factor should be regarded as a major clue for deciding therapy.

Adult↗
PubMed2001

The tolerance and efficacy of interferon-alpha in haemodialysis patients with HCV infection: a multicentre, prospective study.

BACKGROUND: A prospective multicentre study was initiated in HCV-infected haemodialysis patients to assess the tolerance and efficacy of alpha-2b interferon. METHODS: We had planned to include 120 patients with HCV RNA detectable by polymerase chain reaction (PCR) (Amplicor Roche) and histologically documented chronic hepatitis. The dose of alpha-interferon was 3 million units (MU) three times weekly (TTW), to be reduced to 1.5 MU TTW in case of side-effects. Tolerance was evaluated monthly; virological efficacy was evaluated by PCR. A liver biopsy was performed at month 18 (M18). RESULTS: (a) TOLERANCE: After 37 patients had been included, the study was discontinued by the promoting institution because of severe side-effects requiring that treatment be stopped in 19 patients. The side-effects were: cardiac (4) neuropsychiatric (2), digestive (3), acute necrosis of the graft (1), severe asthenia (9), minor side-effects were observed in 22 patients. A complete 12-month course was completed in 12 patients for the 3 MU TTW dose and in six patients for the 1.5 MU TTW reduced dose. Normal ALT level (OR, 0.16; CI 95%, 0.03-0.89) at inclusion was associated with interruption of treatment (univariate analysis). (b) EFFICACY: Sustained virological response was observed in only seven (18.9%), of the 18 patients who completed the treatment (38%). Increased ALT at inclusion (OR, 1.04; CI 95%, 1.01-1.09) and cumulated doses of interferon (OR, 1.01; CI 95%, 1.004-1.026) were jointly associated with a sustained response, while positive PCR at M2 was strongly predictive of treatment failure. CONCLUSION: Tolerance of interferon is poor in haemodialysis patients. Sustained response is fairly high in patients who have 12 months of treatment and seems to be based on the immune status of the patients (ALT) and the cumulative doses of interferon.

Adult↗
PubMed2001

[Prevention and treatment of viral hepatitis in renal insufficiency conditions].

Viral hepatotropic infections may lead to diagnostic and therapeutic problems in hemodialysis patients and kidney recipients. The parenteral and community-acquired routes of contamination of hepatitis B and C viruses explain their high frequency in this population. Their impact, because the immunosuppressive treatments, is harmful with a decrease in patients and allografts survival; cirrhosis is a contra-indication for renal transplantation since associated with a bad short-term prognosis and may require a combined kidney-liver transplantation. Thus, a liver biopsy is recommended in order to evaluate the histopathological severity of the liver disease (stage and grade) and to precise if an antiviral treatment appears necessary, especially because interferon-alpha, the main treatment of hepatitis B and C infections, is contra-indicated in kidney recipients because of the risk of graft rejection. In summary, the diagnosis of viral hepatotropic infections has to be early undergone and its pathological impact has to be evaluated by a liver biopsy. The best treatment has to be prophylactic (vaccination against hepatitis B virus and the respect of universal hygiene rules for hepatitis C virus).

Antiviral Agents↗
PubMed2001

[Hepavir, the first observational study of one cohort of patients treated with alpha-2a interferon, monotherapy. Evaluation of asthenia and its social consequences].

OBJECTIVES: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue. METHODS: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness. RESULTS: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment. CONCLUSION: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Absenteeism↗
PubMed2000

Effect of pregnancy on chronic hepatitis C: a case-control study.

There is evidence of deterioration of hepatitis C after pregnancy. To investigate potential histological changes, we compared liver biopsy samples taken before and after delivery from 12 women positive for hepatitis C virus (HCV) and 12 nonpregnant HCV-positive women. Semiquantitative histopathological measurements showed greater deterioration in cases than in controls (necroinflammatory score deterioration 83.3% vs 25.0%; fibrosis score 41.6% vs 8.3%). This case-control study suggests that pregnancy may worsen HCV-related histopathological injury.

Adult↗