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512 Serotonergic dysfunction during chronic hepatitis C infection among patients with drug addiction compared to controls
Category 5d: Viral Hepatitis: Hepatitis C – Clinical time RT-PCR-based assay was evaluated on the basis of reference panels (AcroMetrix, clinical), and clinical samples (n=100) for testing of sensitivity, specificity, linearity, intra-, inter-assay variability (6-18 repeats) and comparability with COBAS Amplicor Monitor 2.0. HCV-RNA extraction was performed with the high-pure-system (HPS, Roche Diagnostics). The lower detection limit of the COBAS TaqMan was 100% and 72% at 10 and 5 IU/mL, respectively. The specificity was 99% with equal amplification of HCV genotypes 1-6. The mean intra- and inter-assay variability within the range of 7 Mill. to 1000 IU/mL was between a SD of 0.076 and 0.096 log compared to a SD of 0.107 and 0.254 log by the COBAS Amplicor assay. The linearity tests showed a regression coefficient of 0.99 between 7 Mill. and 30 IU/ml. Comparison of HCV RNA quantification by COBAS TaqMan and COBAS Amplicor showed a high concordance with a correlation coefficient of 0.95. The new COBAS TaqMan assay is a highly sensitive, precise, and linear assay for HCV RNA quantification and has the potential to be used instead of previous qualitative and quantitative measurements before, during and after antiviral therapy.
512 SEROTONERGIC DYSFUNCTION DURING CHRONIC HEPATITIS C INFECTION AMONG PATIENTS WITH DRUG ADDICTION COMPARED TO CONTROLS
M. Schaefer 1 , M. Schwaiger 1 , M. Pich 1 , E. Franke 1 , R. Uebelhack 1 , A. Heinz 1 , F. Van Boemmel 2 , T. Berg 2 . 1 Deparment of Psychiatry-CCM, Charite-University Medicine Berlin, Campus Charite Mitte, Berlin, Germany; 2 Department of Gastroenterology-CCV, Charite-University Medicine Berlin, Campus Charite Virchow, Berlin, Germany Chronic hepatitis C infection is associated with an increased incidence of depression in patients with or without drug addiction. Serotonergic dysfunction seems to be one major cause of depression. We investigated in the question, if a chronic hepatitis C virus (HCV)-infection itself or the methadone treatment modulates serotonergic metabolism by using the peripheral platelet model. Method: In a prospective controlled study we measured 5-HT concentration, 5-HT uptake and MAO-B activity at a low physiological substrate concentration in platelets. 22 healthy non HCV-infected controls and 90 HCV-infected control patients without drug abuse were compared with 24 HCV-infected patients during methadone substitution treatment and 6 HCV infected drug users without methadone. Results: Serotonine uptake was significantly lower in HCV-infected control patients without drug abuse compared to non HCV-infected controls. However, drug addicts showed lower serotonine uptake compared to both control groups independent from methadone substitution. Serotonine concentration was significantly lower in drug addicts compared to both control groups. MAO-B activity was decreased in HCV-infected patients compared to non HCV infected controls, while HCV-infected drug users did not differ to HCV-infected controls. We found no differences regarding tryptophan concentrations. Conclusion: HCV-infection, but not methadone substitution influences significantly serotonine metabolism in platelets. Serotonergic deficit seems to be significantly involved the increased incidence of depression during chronic HCV-infection.
513 RELATIONSHIP BETWEEN GENETIC VARIABILTY OF HEPATITIS C VIRUS CORE GENE AND B CELL PROLIFERATION IN CHRONICALLY INFECTED-PATIENTS
D. Sene 1 , P. Cacoub 2 , L. Vallat 4 , A. Cahour 1 , P. Ghillani 5 , Y. Benhamou 3 , J.C. Piette 2 , V. Thibault 1 . 1 Virology, 2 Internal Medicine, 3 Hepato-Gastro-Enterology, 4 Hematology, 5 Immunology, Hopital Pitie-Salpetriere, Paris, France Objective: To explore the possible relationship between the variability of the HCV core coding region and the occurrence of HCV-related B cell proliferation (BCP).
151
Patients and Methods: The whole core coding gene was studied in chronically HCV-infected patients who had either a clonal B cell proliferation (group I, n=15) or no evidence of BCP (group II, n=5). A 519 base pair (nt. 342-850) fragment was PCR amplified and cloned. Phylogenetic and molecular evolutionary analyses were performed on 16 cDNA clones per patient using Mega software. Results: Analysis of the 274 obtained sequences showed that they shared the same amino-acid in 76% of positions independently of the genotype. No difference between the 2 groups was seen with regard to genetic diversity (I: 0.0096±0.004 vs II: 0.006±0.004; p=0.2), proportion of synonymous to non synonymous substitutions (I: 0.407±0.45 vs II: 0.331±0.26; p=0.5) and protein sequence diversity (I: 0.011±0.004 vs II: 0.0065±0.005; p=0.1). Overall comparative analysis failed to identify mutations clearly associated with BCP. However, for genotype 1 sequences, a threonine at position 55 was found in 44% (4/9) vs 0% (0/2) in patients from group I vs II, respectively. Phylogenetic analyses performed on full or partial regions of the core gene were rather influenced by the genotype than the BCP status of the patients. Conclusion: HCV-induced BCP does not seem to be associated with a particular core protein motive. In genotype 1, a threonine at position 55 was found solely in BCP patients. These findings need to be confirmed on larger studies.
514 WEIGHT LOSS DURING PEGYLATED INTERFERON AND RIBAVIRIN TREATMENT OF HEPATITIS C
M. Seyam, D.A. Freshwater, K. O’Donnell, D.J. Mutimer. The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK Interferon treatment of HCV is associated with significant side-effects including weight loss. To date the magnitude, time-course and determinants of weight loss have not been reported. The aim of our study was to describe the evolution of body weight during combination antiviral treatment and to examine possible determinants of weight loss including response to therapy Methods: A retrospective analysis was performed of patients who received combination therapy at our hospital. Body weight was recorded at each outpatient attendance during treatment. Weight during treatment was expressed as a percentage of baseline body weight. Results: Data from 125 patients were included. We observed a decline of body weight during treatment – median (range) values @ 4, 12,24,48 weeks (expressed as % of baseline weight) were 97.7(91.5-110.2), 95.6(84.4109.4), 93.7(80.8-102.2), 91.8(80.1-101.9)% respectively. Those patients who experienced weight loss greater than the median percentage at week 24 were found to have a statistically significant higher pre-treatment weight compared to those who lost less (mean baseline weight 81.73kg v 73.69kg, p=0.03). There was no significant association of weight loss with age, gender, ethnicity, pre-treatment histological stage, cumulative IFN dose (adjusted for body weight), HCV genotype or treatment outcome. Conclusions: Patients experienced significant weight loss with median losses of 6.3% and 8.2% during 24 and 48 weeks respectively. Greater rate of weight loss is experienced by those with higher baseline weight. Weight loss was not associated with IFN dose/kg body weight. Those experiencing greater weight loss during therapy did not benefit from improved antiviral response.
512 SEROTONERGIC DYSFUNCTION DURING CHRONIC HEPATITIS C INFECTION AMONG PATIENTS WITH DRUG ADDICTION COMPARED TO CONTROLS
M. Schaefer 1 , M. Schwaiger 1 , M. Pich 1 , E. Franke 1 , R. Uebelhack 1 , A. Heinz 1 , F. Van Boemmel 2 , T. Berg 2 . 1 Deparment of Psychiatry-CCM, Charite-University Medicine Berlin, Campus Charite Mitte, Berlin, Germany; 2 Department of Gastroenterology-CCV, Charite-University Medicine Berlin, Campus Charite Virchow, Berlin, Germany Chronic hepatitis C infection is associated with an increased incidence of depression in patients with or without drug addiction. Serotonergic dysfunction seems to be one major cause of depression. We investigated in the question, if a chronic hepatitis C virus (HCV)-infection itself or the methadone treatment modulates serotonergic metabolism by using the peripheral platelet model. Method: In a prospective controlled study we measured 5-HT concentration, 5-HT uptake and MAO-B activity at a low physiological substrate concentration in platelets. 22 healthy non HCV-infected controls and 90 HCV-infected control patients without drug abuse were compared with 24 HCV-infected patients during methadone substitution treatment and 6 HCV infected drug users without methadone. Results: Serotonine uptake was significantly lower in HCV-infected control patients without drug abuse compared to non HCV-infected controls. However, drug addicts showed lower serotonine uptake compared to both control groups independent from methadone substitution. Serotonine concentration was significantly lower in drug addicts compared to both control groups. MAO-B activity was decreased in HCV-infected patients compared to non HCV infected controls, while HCV-infected drug users did not differ to HCV-infected controls. We found no differences regarding tryptophan concentrations. Conclusion: HCV-infection, but not methadone substitution influences significantly serotonine metabolism in platelets. Serotonergic deficit seems to be significantly involved the increased incidence of depression during chronic HCV-infection.
513 RELATIONSHIP BETWEEN GENETIC VARIABILTY OF HEPATITIS C VIRUS CORE GENE AND B CELL PROLIFERATION IN CHRONICALLY INFECTED-PATIENTS
D. Sene 1 , P. Cacoub 2 , L. Vallat 4 , A. Cahour 1 , P. Ghillani 5 , Y. Benhamou 3 , J.C. Piette 2 , V. Thibault 1 . 1 Virology, 2 Internal Medicine, 3 Hepato-Gastro-Enterology, 4 Hematology, 5 Immunology, Hopital Pitie-Salpetriere, Paris, France Objective: To explore the possible relationship between the variability of the HCV core coding region and the occurrence of HCV-related B cell proliferation (BCP).
151
Patients and Methods: The whole core coding gene was studied in chronically HCV-infected patients who had either a clonal B cell proliferation (group I, n=15) or no evidence of BCP (group II, n=5). A 519 base pair (nt. 342-850) fragment was PCR amplified and cloned. Phylogenetic and molecular evolutionary analyses were performed on 16 cDNA clones per patient using Mega software. Results: Analysis of the 274 obtained sequences showed that they shared the same amino-acid in 76% of positions independently of the genotype. No difference between the 2 groups was seen with regard to genetic diversity (I: 0.0096±0.004 vs II: 0.006±0.004; p=0.2), proportion of synonymous to non synonymous substitutions (I: 0.407±0.45 vs II: 0.331±0.26; p=0.5) and protein sequence diversity (I: 0.011±0.004 vs II: 0.0065±0.005; p=0.1). Overall comparative analysis failed to identify mutations clearly associated with BCP. However, for genotype 1 sequences, a threonine at position 55 was found in 44% (4/9) vs 0% (0/2) in patients from group I vs II, respectively. Phylogenetic analyses performed on full or partial regions of the core gene were rather influenced by the genotype than the BCP status of the patients. Conclusion: HCV-induced BCP does not seem to be associated with a particular core protein motive. In genotype 1, a threonine at position 55 was found solely in BCP patients. These findings need to be confirmed on larger studies.
514 WEIGHT LOSS DURING PEGYLATED INTERFERON AND RIBAVIRIN TREATMENT OF HEPATITIS C
M. Seyam, D.A. Freshwater, K. O’Donnell, D.J. Mutimer. The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK Interferon treatment of HCV is associated with significant side-effects including weight loss. To date the magnitude, time-course and determinants of weight loss have not been reported. The aim of our study was to describe the evolution of body weight during combination antiviral treatment and to examine possible determinants of weight loss including response to therapy Methods: A retrospective analysis was performed of patients who received combination therapy at our hospital. Body weight was recorded at each outpatient attendance during treatment. Weight during treatment was expressed as a percentage of baseline body weight. Results: Data from 125 patients were included. We observed a decline of body weight during treatment – median (range) values @ 4, 12,24,48 weeks (expressed as % of baseline weight) were 97.7(91.5-110.2), 95.6(84.4109.4), 93.7(80.8-102.2), 91.8(80.1-101.9)% respectively. Those patients who experienced weight loss greater than the median percentage at week 24 were found to have a statistically significant higher pre-treatment weight compared to those who lost less (mean baseline weight 81.73kg v 73.69kg, p=0.03). There was no significant association of weight loss with age, gender, ethnicity, pre-treatment histological stage, cumulative IFN dose (adjusted for body weight), HCV genotype or treatment outcome. Conclusions: Patients experienced significant weight loss with median losses of 6.3% and 8.2% during 24 and 48 weeks respectively. Greater rate of weight loss is experienced by those with higher baseline weight. Weight loss was not associated with IFN dose/kg body weight. Those experiencing greater weight loss during therapy did not benefit from improved antiviral response.