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Biomedical subjects

S Pol

Publications and source records attributed to S Pol.

At least 73 records · Page 4Linked to original sources
PubMed1999

Specific vaccine therapy in chronic hepatitis B: induction of T cell proliferative responses specific for envelope antigens.

In a pilot study, it was established that specific therapy by standard anti-hepatitis B virus (HBV) vaccination may be effective in reducing HBV replication and canceling the immune tolerance to hepatitis B surface antigen (HBsAg) particles in about 50% of persons with chronic active HBV replication. In the present study, the vaccine-induced immune responses were analyzed during an ongoing controlled multicenter vaccine trial. Vaccination elicited peripheral blood mononuclear cell proliferative responses specific for envelope antigen in 7 of 27 subjects given HBsAg. The responses induced by the vaccines were mediated by CD4+ T lymphocytes, and at least three different epitopes were recognized. HBV-specific CD4+ T lymphocytes produced high levels of interferon-gamma [corrected] and belonged to a T helper 1 subset. Reduction of serum HBV DNA in some of these persons suggests that induction of CD4+ T cell responses could be important in controlling viremia during vaccine therapy of chronic HBV carriers.

Epitopes↗
PubMed1999

Significance of repeatedly normal aminotransferase activities in HCV-infected patients.

The significance of repeatedly normal serum aminotransferase activities in antihepatitis C virus (anti-HCV)-positive patients is not clear. To address this issue, the authors analyzed clinical, virologic, histopathologic, and biological characteristics of such subjects. Among their active file of 1,200 anti-HCV-positive immunocompetent patients, they identified 36 subjects (3%) with repeatedly normal aminotransferase activities, as defined by at least four normal values of aminotransferase over a minimum period of 6 months without any abnormal value (mean of this period, 31 +/- 21 months). The 36 patients included 11 men and 25 women with a mean age of 45 +/- 15 years. Twenty-three of these 36 subjects (64%) had detectable HCV viremia by polymerase chain reaction. Their genotype distribution was as follows: genotype 1a or 1b, 57%; genotype 2, 26%; and genotype 3, 17%. Of the HCV ribonucleic acid (RNA)-positive and HCV RNA-negative subjects, 17 and 5 had a liver biopsy respectively. In the former, the mean Knodell score was 5.6 +/- 3.5 (range, 1 to 14), and was < 5 in 9 patients (53%) and > or = 5 in 8 (47%), including extensive fibrosis (n = 2) or cirrhosis (n = 2). In the HCV RNA-negative subjects, one patient had a Knodell score > or = 5. Comparing the 23 immunocompetent viremic subjects with repeatedly normal serum aminotransferase activities with our group (n = 564) of immunocompetent viremic patients with abnormal aminotransferase activities, there was a significant predominance of women (70% versus 44%, p < 0.05) and of genotype 2 in the former (26% versus 7%, p < 0.05), but no differences according to quantitative viremia, alcohol consumption, or distribution of risk factor were observed. Most of viremic HCV-infected patients with long-term and repeatedly normal aminotransferase values have indeed chronic active hepatitis, including extensive fibrosis or cirrhosis in as many as 20% of patients. This emphasizes the need for serum HCV RNA determination in anti-HCV-positive patients with normal aminotransferase activities. In these patients liver biopsy may be necessary and should be discussed.

Adolescent↗
PubMed1999

Epidemiological and virological analysis of couples infected with hepatitis C virus.

BACKGROUND: If transmission of hepatitis C virus (HCV) infection through parenteral exposure is well documented, sexual transmission of HCV is still debated. AIMS: To perform extensive epidemiological and virological analysis in 24 couples in which each spouse was anti-HCV positive in order to delineate more precisely potential sexual transmission of HCV. PATIENTS: Twenty four couples in which each partner was anti-HCV positive. These 48 spouses were recruited in a liver unit by regular screening of spouses of index patients. METHODS: All 48 spouses completed an epidemiological questionnaire on risk factors for HCV. Qualitative detection of serum HCV RNA and determination of HCV type by genotyping and serotyping were performed. Sequence analysis of HCV strains by phylogenetic analysis was carried out in seven couples with concordant genotypes. RESULTS: The mean (SD) partnership duration was 12 (10) years. Serum HCV RNA was detected in both partners in 18 of the couples (75%) and in only one partner in six of the couples (25%). HCV typing showed concordant genotypes in 12 couples (50%), discordant genotypes in seven (29%), and in the other five couples (21%) only one spouse could be genotyped. Of the 48 spouses, 33 had a major risk factor for HCV transmission such as transfusion (n = 6) and intravenous drug use (n = 27). Eleven of the 12 couples infected with the same HCV genotype had at least one parenteral risk factor for viral transmission in both spouses. Whatever the genotype concordance, in most couples (75%), both spouses showed parenteral risk factors for viral transmission. Sequence analysis of HCV strains was possible in seven of 12 couples with identical genotype and showed different and identical isolates in four and three couples respectively. CONCLUSION: The study emphasises the risk of overestimating the importance of a very low sexual HCV transmission risk as against other, mainly parenteral, risk factors.

Adult↗
PubMed1999

Treatment of chronic hepatitis C in special groups.

Little is known about treatment of hepatitis C virus (HCV) infection in "other groups" than the general population, namely patients with hematologic or renal disorders and patients with human immune deficiency (HIV) co-infection. The aim was to better define HCV therapies in these groups. We analyzed the medical literature focusing on treatment of HCV infection in other populations to suggest conclusions about indications based on tolerance and efficacy. As in the general population, the decision to treat should be based mainly on liver pathology, and to a lesser extent on virologic profiles (genotype, quantitative viremia). Hemophilia does not modify therapeutic strategies which combine interferon-alpha and ribavirin. Similar combinations should be discussed in patients with inherited hemoglobin disorders but iron overload (secondary hemochromatosis) associated with multiple transfusions may decrease the potential efficacy of interferon-alpha and chronic anemia may limit the use of ribavirin. In hemodialyzed patients, therapy by interferon-alpha is feasible with 3 MU subcutaneously after each hemodialysis three times weekly for 6-12 months. Virologic results are at least similar to those obtained in the general population with frequent pathological improvement. Combinations are not possible because ribavirin is contraindicated for pharmacokinetic reasons. In kidney recipients, interferon-alpha is deleterious and inefficient; ribavirin monotherapy has a potential interest which remains to be evaluated. In HIV co-infected patients, treatment is mandatory given the high rate of cirrhosis and the improved survival related to multiple anti-HIV therapies (which have no clear efficacy for quantitative HCV viremia). Due to the limited efficacy of interferon-alpha monotherapy, the combination of interferon-alpha and ribavirin appears to be the logical treatment. An important point is the in vitro inhibition of phosphorylation by ribavirin of HIV reverse transcriptase inhibitors which has to be analyzed in vivo before the combination can be recommended. On the basis of the results of liver biopsy, antiviral treatments may be proposed for HCV-infected patients with hematologic or renal disorders as well as for HIV co-infected patients. The choice of therapy (monotherapy or combined therapies) should be based on the clinical situation (contraindicated with chronic anemia or renal failure, for example) and its duration on the virologic factors of response as in the general population.

Antiviral Agents↗
PubMed1998

Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients.

BACKGROUND: The long-term impact of hepatitis C virus (HCV) infection in renal transplant recipients remains controversial. We report here our experience, in a homogeneous single center, of 499 patients with a fairly long follow-up. METHODS: We retrospectively studied 499 hepatitis B virus-negative patients who received an initial cadaver donor kidney transplantation at Necker Hospital between January 1, 1979 and December 31, 1994, with a graft or patient survival of at least 6 months. Anti-HCV antibodies were detected at time of transplantation in 112 patients (22%). Patient survival and causes of death were compared among anti-HCV-positive and -negative patients RESULTS: Our results clearly indicate that first cadaver kidney transplant recipients with anti-HCV antibodies had a significantly shorter patient and graft long-term survival than recipients without anti-HCV antibodies (P<0.01 and P<0.0001 respectively). Mean follow-up time after transplantation was 79+/-2 months in the former group and 81+/-5 months in the latter (NS). Increased mortality was primarily caused by liver disease (P<0.001) and sepsis (P<0.01). In a multivariate analysis, HCV infection significantly affected the mortality rate (odds ratio: 2.8). CONCLUSIONS: These results suggest that HCV infection has a harmful long-term impact on the survival of kidney transplant recipients.

Adult↗
PubMed1998

Predictive factors for development of cirrhosis in parenterally acquired chronic hepatitis C: a comparison between immunocompetent and immunocompromised patients.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact of the host immune status and of virological and environmental parameters on the development of cirrhosis during chronic hepatitis C virus infection. METHODS: Liver histology (cirrhosis or not, Knodell score) was evaluated according to age, sex, route and age of contamination, alcohol consumption and immune status in a large series of 553 HBsAg-negative patients (whose duration of hepatitis C virus infection could be precisely evaluated) divided into three groups: group 1 consisted of 462 immunocompetent subjects (46.1% intravenous drug users, 53.9% transfused), infected for a mean of 12.5+/-6.7 years, including 16.6% of alcohol abusers (>80 g/day); groups 2a and 2b consisted of 91 immunocompromised patients, 52 human immunodeficiency virus-coinfected patients corresponding to group 2a and 39 kidney recipients undergoing immunosuppressive therapy for group 2b, having been infected by hepatitis C virus for a mean of 12.6+/-5.3 and 11.5+/-5.3 years, respectively. RESULTS: Group 1: cirrhosis was present in 11.0% of group 1 patients and in 23.6% of immunocompetent patients with a duration of hepatitis C virus infection of 20 years or more. Forty-three percent of patients with cirrhosis and with hepatitis C virus infection for more than 20 years were alcohol abusers. The time taken to develop cirrhosis was 14+/-7 years in patients infected before the age of 40 years as compared to 8+/-5 years in those infected after 40 years (p<0.001). Groups 2a and 2b: cirrhosis was present in 19.8% of immunocompromised patients, a significantly higher rate than in immunocompetent patients (p<0.01). Alcohol abuse did not increase the risk of cirrhosis in this group. All patients but one were infected by hepatitis C virus before the age of 40 and the calculated time elapsed until the occurrence of cirrhosis was 12.4+/-5.5 years. In groups 1, 2a and 2b, there was no relation between histological severity, hepatitis C virus genotype and viral load. Four variables were independently associated with the occurrence of cirrhosis in the multivariate analysis: age over 40 at time of contamination (RR=9.3 in age range 40 to 59 and 91.2 in > or =60 years); long duration (> or =20 years) of hepatitis C virus infection (RR=15.4); alcohol consumption over 80 g/d (RR=2.9); and human immunodeficiency virus-coinfection (RR=2.6). CONCLUSIONS: Our study on a large series of well-characterized patients provides an accurate evaluation of the risk of cirrhosis in parenterally-contaminated immunocompetent hepatitis C virus-infected patients, with an overall figure of 11%. It also demonstrates the impact of the host immune status on the risk of severe histological lesions during chronic hepatitis C virus infection. It finally establishes the importance of age at the time of viral infection in the occurrence of cirrhosis, as well as the importance of alcohol consumption. Thus, at least following parenteral infection, both host-related and environmental cofactors play a major role in the severity of the liver lesions associated with hepatitis C virus infection.

Adult↗
PubMed1998

Hepatitis C virus (HCV) hypervariable region 1 complexity does not correlate with severity of liver disease, HCV type, viral load or duration of infection.

BACKGROUND/AIMS: Several studies have suggested that infection with a highly heterogeneous population of hepatitis C virus correlates with a low response rate to interferon. It is still debated, however, whether or not this heterogeneity might be associated with liver disease severity. The aim of this study was to analyse hepatitis C virus genome complexity in patients with various stages of liver disease. METHODS: We used polymerase chain reaction-single strand conformation polymorphism (SSCP) analysis to estimate the degree of complexity of the hypervariable region (HVR1) in 95 anti-HCV and serum HCV-RNA positive patients. They were divided into two groups according to Knodell's histological activity index (HAI) grading: 22 with HAI <4 and 73 with HAI> or =4, including 19 with cirrhosis. RESULTS: The number of visible SSCP bands ranged from 1 to 7. There was no significant difference in the number of SSCP bands between patients with HAI <4 and patients with HAI> or =4 (median number of bands was 4 in both groups). The number of SSCP bands was not correlated to the biochemical activity, the genotype, the HCV-RNA titre or the duration of hepatitis C virus infection. CONCLUSIONS: The HCV-HVR1 complexity profile alone does not correlate with the severity of liver disease, whatever the biological and virological profile of the viral infection.

Female↗
PubMed1998

Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users.

BACKGROUND/AIM: This retrospective study aimed to better define the respective biological and pathological impact of human immunodeficiency virus infection and chronic alcohol consumption on the course of hepatitis C virus infection in intravenous drug users. METHODS: Two hundred and ten consecutive anti-HCV positive intravenous drug users, among whom 60 were also anti-HIV positive, took part in the study at the University Hospital, Paris, France. RESULTS: The activity of aspartate aminotransferase and gamma-glutamyl transpeptidase was significantly increased in serum from anti-HIV positive patients. The mean hepatitis activity index was significantly higher in anti-HIV positive patients (p<0.05), among whom there was also a higher proportion of patients with cirrhosis as compared to anti-HIV negative patients (30.0 vs 15.3%, p<0.0001). Excessive alcohol drinking (recorded in around 35% of the patients, whatever their HIV status), as compared to non-excessive drinking, was more often associated with cirrhosis in anti-HIV negative (24.5 vs 11.3%, p<0.05) than in anti-HIV positive patients (30.4 vs 29.7%, not significant). In a multivariate analysis, HIV infection (relative risk 2.2, confidence interval 1.1-4.5) and excessive alcohol drinking (relative risk 1.9, confidence interval 1.0-3.9) were the variables independently associated with the risk of cirrhosis. CONCLUSION: Human immunodeficiency virus infection worsens the course of chronic hepatitis C in intravenous drug users. Excessive alcohol drinking also appears to be a crucial negative cofactor, and therefore alcohol withdrawal should be proposed as an integral part of the therapy.

Adult↗
PubMed1998

[Interactions between the human immunodeficiency virus and hepatitis C virus].

INTRODUCTION: Prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected subjects is around 9%, varying according to the mode of contamination. Reciprocal interactions between the two viruses have to be evaluated. CURRENT KNOWLEDGE AND KEY POINTS: HCV infection is usually associated with chronic hepatitis and detectable viremia in HIV-infected patients. HIV infection enhances HCV replication, leading to more severe liver lesions and to a more rapid occurrence of cirrhosis. This underlines the need for both early diagnosis and therapy in order to avoid severe evolution of the liver disease. FUTURE PROSPECTS AND PROJECTS: Even though the rate of long-term responses to interferon alpha is low, improvement may be expected from combined therapies, especially with combination including ribavirin. The impact of both antiretroviral triple therapy and accompanying immune restoration on natural history and treatment of HCV infection has to be assessed, as the above mentioned consensual conclusions may be modified in a near future.

Anti-HIV Agents↗
PubMed1998

Hepatitis G virus infection in hepatitis C virus-positive patients co-infected or not with hepatitis B virus and/or human immunodeficiency virus.

This was a retrospective study to evaluate the prevalence and impact of hepatitis G virus (HGV) infection in hepatitis C virus (HCV)-positive drug addicts, according to the serological status of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. Two hundred and thirty-five randomly selected intravenous drug addicted patients (147 French, 88 Italian) were studied. All patients were positive for antibodies to HCV (anti-HCV). HGV RNA positivity was measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Comparisons of HCV RNA positivity rate, and biological and histopathological variables, were made between HGV RNA-positive and negative patients, according to their HBV and HIV status. HGV prevalence was around 30% in both French and Italian groups. No clear association between HGV infection and a particular HCV genotype was observed. The rate of HCV RNA positivity did not differ between HGV-positive and HGV-negative patients after stratification for hepatitis B surface antigen (HBsAg) and HIV positivity. Histological severity of the underlying chronic hepatitis did not differ according to the HGV status; however, in HIV-positive HBsAg-negative patients, the hepatitis activity was moderately increased in HGV-positive patients. A striking negative influence of HBsAg positivity on HCV replication was observed in HIV-negative patients; an HCV RNA-positive rate of 25% was found in HBsAg-positive patients vs 86% in HBsAg-negative patients; similar significant results were observed in HIV-positive patients, although to a lesser extent. The underlying chronic hepatitis was significantly more severe in HBsAg-positive than in HBsAg-negative HIV-negative patients. Hence, HGV infection is highly prevalent in anti-HCV positive drug addicts but the co-infection with HCV does not seem to influence HCV replication nor to worsen the underlying chronic hepatitis, in HIV-negative patients at least. Reciprocal influence between HBV, HCV and HIV appears rather complex, HBsAg carriage seeming to exert per se a negative effect on HCV replication, particularly in HIV-negative patients, suggesting that interactions between hepatitis viruses should always be analysed in the light of HIV status.

Adult↗
PubMed1998

Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy.

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis of human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. The precise impact, if any, of anti-HIV triple therapy on hepatitis C virus (HCV) infection is unknown. We describe an unusual case of rapidly evolving HCV-related cirrhosis that paralleled restoration of immune status in an HIV-infected patient and discuss the possible link between such a severe course of hepatitis C and anti-HIV triple therapy.

Adult↗
PubMed1998

Tritherapy for human immunodeficiency virus infection does not modify replication of hepatitis C virus in coinfected subjects.

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis for human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. In an attempt to evaluate the impact of anti-HIV triple combination therapy on the course of hepatitis C virus (HCV)-related chronic hepatitis and on HCV replication, we studied the biological and virological characteristics of 22 HCV/HIV-coinfected patients who were given triple combination therapy. In comparison with baseline values, there was (1) a significant increase in the CD4 and CD8 cell counts and a decrease in the HIV RNA load and (2) no significant variation in aminotransferase activities or the HCV RNA load at 3, 6, or 9 months of tritherapy. Antiretroviral tritherapy seems to modify neither the biological activity of HCV-related chronic hepatitis nor the HCV load, despite immune restoration. Hepatic histopathologic analysis is warranted to assess the impact of immune restoration on liver lesions.

Adult↗
PubMed1998

Characteristics and treatment of hepatitis C virus infection in HIV-coinfected subjects.

Hepatitis C virus (HCV) and HIV share the same parenteral routes of transmission. This common epidemiology explains the high frequency of combined infections by HCV and HIV. The aim of this review is to clarify some important issues dealing with the reciprocal impact of HIV and HCV-associated infections, including the variations in clinical, biologic, histopathologic, and virologic natural history of both infections. Insights gained may improve clinical care of and the therapeutic approach to HCV infection in HIV-coinfected subjects.

Genotype↗
PubMed1998

Overactivity of cervical premotor neurons in Parkinson's disease.

OBJECTIVES: Cortical command to upper limb motor neurons is transmitted, in humans, not only through the monosynaptic corticomotor neuronal pathway, but also through cervical premotor neurons. Whether activity in this non-monosynaptic corticospinal pathway is modified in Parkinson's disease was explored. METHODS: Ongoing EMG activity recorded in wrist extensors during tonic extension of the wrist is suppressed by a volley evoked by stimulating the superficial radial nerve. It has been shown that this cutaneous induced suppression is due to inhibition of transmission of the cortical command at a premotor neuronal level. By comparing the cutaneous induced EMG depression between 45 de novo parkinsonian patients and 23 age matched controls it has been possible to appreciate if and to what extent the "non-monosynaptic" part of the cortical command is modified in these patients. RESULTS: At the early stage of the illness the EMG depression, reflecting the "non-monosynaptic" part of the cortical command, was bilaterally increased despite very asymmetric clinical status. When the duration of the disease was more than 36 months, EMG depression returned to its control level. No correlation was found between the amount of the EMG depression and parkinsonian symptoms before and after levodopa treatment. CONCLUSION: Increase of the relative "non-monosynaptic" part of the cortical command could reflect a compensatory motor mechanism elaborated upstream from the motor cortex.

Antiparkinson Agents↗