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Biomedical subjects

B Nalpas

Publications and source records attributed to B Nalpas.

At least 19 recordsLinked to original sources

Financial costs of alcoholism treatment programs: a longitudinal and comparative evaluation among four specialized centers.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

Adult↗

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↗

[Peripheral markers, future perspectives].

Four of the recently described peripheral markers of alcohol abuse have been reviewed. The acetaldehyde adducts allow to detect an alcohol abuse lasting for several weeks, even after a recent alcohol withdrawal. Inversely, 5-hydroxytryptophol (5-HTOL) reflects the alcohol consumption of the last 24 hours. Its detection is possible after the blood alcohol concentration has disappeared. Its measurement is run in urine samples, thus without invasive sampling. The hyaluronic acid and the activity of beta-hexosaminidase are markers of hepatobiliary alcohol induced disorders more than direct markers of alcohol intake. Acetaldehyde adducts could be used as markers of long term alcohol abuse, CDT as a marker of the recent alcohol abuse, and 5-HTOL the detection of alcohol abuse of the past day.

Acetaldehyde↗

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↗

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↗

Combination of ribavirin and interferon-alfa surpasses high doses of interferon-alfa alone in patients with genotype-1b-related chronic hepatitis C.

The purpose of this study was to compare interferon-alfa alone (12-month course with high initial doses) with a combination of interferon-alfa and ribavirin in patients infected with genotype 1b. Three hundred and seven patients were randomized into 3 groups to receive 6 mega units (MU) of interferon-alfa-2b subcutaneously 3 times weekly for 6 months followed by 3 MU for 6 months (n = 95, group A); 10 MU for 3 months followed by 6 MU for 3 months, followed by 3 MU for 6 months (n = 83, group B); or the group-A schedule in combination with ribavirin (n = 129, group C) for 4 (n = 46), 6 (n = 44), or 12 months (n = 39). Negative polymerase chain reaction (PCR) was more frequent in group C than in groups A or B after 3 months of treatment (P <.006), at the end of treatment (P =.017), and at the end of follow-up (32.8%, 16.9%, and 14.1%, respectively, P <.003). A complete response (negative PCR and normal alanine transaminase) was higher in group C than in the other groups and when comparing 12- to 4- and 6-month combination therapy at the end of treatment (P =.05) and of follow-up (45.2% vs. 25.4%, respectively, P =.05). The greater efficacy of the combination was related to the higher rate of primary virological response and also to a decrease in the percentage of breakthrough and of relapse. In 1b-infected patients, the combination of high doses of interferon-alfa (6 MU) and ribavirin for 12 months appears to be the best therapy, with a high rate of sustained response.

Adult↗

Detection of circulating prostate derived cells in patients with prostate adenocarcinoma is an independent risk factor for tumor recurrence.

PURPOSE: To determine whether the presence of prostate-derived cells in the peripheral blood circulation is a marker of prostate cancer and to define the clinical impact of the test. MATERIALS AND METHODS: We tested the peripheral blood of 99 patients with prostate adenocarcinoma (PAC), 79 of them undergoing radical prostatectomy, and 92 controls (31 healthy volunteers, 50 patients with adenoma and 11 with prostatitis) using a highly controlled procedure including reverse-transcriptase polymerase chain reaction (RT-PCR) targeted to prostate-specific antigen (PSA) mRNA. Patients were followed for 26 +/- 12 (range: 4 to 49) months. Forty tumor tissues were analyzed by immunohistochemistry for expression of p53 and E-cadherin antigens. RESULTS: Thirty three (33%) patients with PAC and 2 (2%) controls scored positive (p <0.0001) for the test. Detection of circulating prostatic cells was associated with development of metastases (p <0. 001), with relapse (p <0.001) and with a serum PSA level at diagnosis higher than 15 ng./ml. (p = 0.009). The rate of development of metastases according to time was significantly higher in patients who scored positive for the test (p <0.04). In a multivariate analysis, only the RT-PCR test was an independent risk factor associated with relapse (RR: 6.7). Finally, E-cadherin expression was significantly lower in the tumor tissues of positive patients as compared with those who scored negative for the test (p <0.01). CONCLUSIONS: This RT-PCR procedure, performed at diagnosis and with appropriate controls, is a clinically useful assay in evaluating the risk of tumor recurrence after radical prostatectomy in patients with PAC.

Adenocarcinoma↗

[Prevalence of infection by hepatitis viruses in a rural area. Analysis according to risk factors and alcohol consumption].

OBJECTIVES: To evaluate the prevalence of serum markers of hepatitis A, B and C viruses in a rural area according to risk factors and alcohol consumption. METHODS: Transversal study of unselected subjects living and working in a rural area. Each subject included was asked to fill out an anonymous self-administered questionnaire dealing with his own risk factors, sexual behaviour and alcohol consumption. A blood sample was collected for detection of HBsAg, anti-HBc, anti-HBs, anti-HAV and anti-HCV antibodies. RESULTS: Three hundred three subjects with a mean age of 48 years were included. Main risk factors for viral infection were: blood transfusion (9.4%), intravenous drug addiction (0.73%), acupuncture (17.5%), tattoos (5. 8%), past hospitalizations (71.5%), homosexuality (1.1%), conjugal unfaithfulness (11%), sexual partners >5 (21.3%). Most subjects with at risk sexual behaviour had sexual relations without protection. Anti-HAV prevalence was 87.2% (95% confidence interval 83.4-91.0%). None of the subjects was HBsAg positive and 6.0% (confidence interval 4.7-8.7%) had anti-HBV antibodies. HBV prevalence was correlated to homosexuality only. Two subjects (0.67%, confidence interval 0-1.6%) without any identified risk factor had anti-HCV antibodies. There was no correlation between serum viral marker positivity and an excess alcohol consumption (>80 g of ethanol/d) which was present in 46 subjects. However HBV prevalence was 28.6% in the seven subjects who had been treated for alcoholism; these 7 subjects had a highly at risk sexual behaviour. CONCLUSION: In a rural area, infection by HAV is very frequent. The prevalence of HBV and HCV did not greatly differ from that observed in the general and urban population. The frequent failure to use protection in subjects with at risk sexual behaviour reinforces the need of prevention programs in rural areas.

Adult↗

Triggering of acute alcoholic hepatitis by alpha-interferon therapy.

BACKGROUND/AIMS: Alcohol may induce autoimmunity by recognition of acetaldehyde-modified proteins which may be implicated in the pathogenicity of acute alcoholic hepatitis. We report here the potential role of alpha-interferon, a potent inducer of the autoimmunity process, in inducing alcoholic hepatitis. METHODS: We analyzed clinical, biological, virological and histological features in two cases where alpha-interferon treatment for HCV-related hepatitis led to a marked increase in aminotransferase activities. RESULTS: alpha-interferon as treatment of HCV-related hepatitis seemed to exacerbate acute alcoholic hepatitis despite moderate alcohol consumption. In Case 1, moderate daily alcohol intake of 40 g during therapy led to biopsy-proven acute alcoholic hepatitis, while the same consumption before therapy did not. In Case 2, before treatment, the liver biopsy showed mild acute alcoholic hepatitis; aminotransferases increased during alpha-interferon therapy, although no increase in alcohol intake was observed. CONCLUSION: alpha-interferon therapy by its immunomodulatory properties could be implicated in alteration of the course of acute alcoholic hepatitis. These observations emphasize that the decision to treat with alpha-interferon when there is even moderate alcohol consumption should be carefully weighted in HCV-infected patients.

Acute Disease↗

Management of hepatitis C by European hepatologists.

In 1996, the French Réseau National de Santé Publique was funded by the Direction General V of the EU to perform a European survey on the epidemiology, the surveillance, the prevention and the management of hepatitis C virus (HCV) infection in the EU member states. This study included two approaches: one consisting of a survey of public health authorities on all the implemented policies dealing with epidemiological status, surveillance and prevention of HCV infection; and the second, in which a large series of hepatologists were interviewed on their own practices with regard to hepatitis C.

Europe↗

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↗

[Alcohol and liver].

The first part of this article is devoted to the metabolism of alcohol and the mechanisms underlying its hepatotoxicity. The second part describes the clinical features of the various patterns of alcohol-related liver disease (ARLD). The third part focuses on the characteristics, semiological value, and limitations of serum markers used in ARLD. Tests used to screen for alcohol abuse (blood alcohol, MCV, GGT, CDT, and FAEE) differ from those used to monitor alcohol withdrawal and to detect early-stage liver disease (ALT, AST, ASTm, alphaGST, and redox status).

Animals↗

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↗

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↗