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The common functional C(−159)T polymorphism of the LPS receptor CD14 does not influence the disease outcome in patients with chronic hepatitis C infection
Category 5: Viral hepatitis: basic aspects ~
CYTOKINE PROFILE IN HCV+ PATIENTS WITH AND WITHOUT CIRRHOSIS
Gabriela Gutierrez t, Socorro Cruz 2, Sara Sixtos 3, Teresa Ramirez 4, Concepcion Gutierrez 5, Graciela Castro 6, Ernesto Roldan 7, Florencia Vargas s, David Kershenobich9 . llnstituto Nacional De Ciencias
Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 21nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 31nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E; 4Instituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E ; 51nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 61nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran ', Mexico D.E ; 71nstituto Nacional De Oencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; Slnstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E; 91nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran ', Mexico D.E, Mexico
Background: The infected peripheral mononuclear blood cells (PMBC)
223
Diskussion: The functional C(-159)T polymorphism of the CD14 gene does not seem to correlate with the degree of liver damage in patients with HepC - different from alcoholic liver disease. This may indicate that LPS mediated signal transduction is less important in this group of patients or may suggest that other mechanism for LPS recognition, such as toll-like receptors, are important in chronic HepC.
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HEPATITIS DELTA ANTIGENS OLIGOMERIZE WITHOUT GENOTYPIC SPECIFICITY BUT VARY WITH TRANS-ACTIVATING EFFICIENCIES BETWEEN GENOTYPES I AND II HDV
Sheng-Chieh Hsu 1,2,3, Jaw-Ching Wu 2,3, Wan-Jr Syu I . 1Institutes of Microbiology and Immunology, National Yang-Ming University, Taipei; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei; 3Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, ROC
may be involved in the selection and persistence of the hepatitis C virus (HCV) genomic variants as well as triggering and maintaining liver fibrosis. Objective: Determine the expression and secretion of cytokines in HCV patients and cirrhotic HCV patients (C-HCV). Method: PMBC from 11 C-HCV and 15 HCV patients were obtained. Cells were cultured during 24 h. IL-lb, TNF-a, IL-8 and IFN-g secretion and expression were determined. RT-PCR for these cytokines was done in liver biopsies. Results: IL-lb secretion was similar in HCV and C-HCV (p = 0.002). IL-1 secretion in C-HCV correlate with IL-8 from HCV patients (p = 0.01). TNF-a secretion was similar in HCV and C-HCV (p -- 0.014). ILlb expression in liver biopsy was high in C-HCV and HCV patients (p = 0.021). There were no correlation between IL-8 and IFN-g. IL-8 secretion and expression in PMBC was elevated in both groups of patients. Conclusions: In chronic hepatitis C, IL-lb play a role in the immune response at injury by HCV. Also the activation of the immune response in hepatitis C was through TNFa and IL-lb. The HCV infection may activate a very specific immune response in the liver to allow chronic infection, which can lead to liver damage, hepatitis and cirrhosis. Thus, this cytokines may be useful in diagnosing and progression of Hepatitis C.
Hepatitis D virus (HDV) has different genotypes that vary in both nucleotides and the encoded delta antigen (HDAg). The small form of HDAg (HDAg-S) supports the viral RNA replication while the large form of HDAg (HDAg-L) is essential for virus assembly. Oligomerization and RNA binding activity of HDAgs are needed for HDV replication and virus particle assembly. Variations in amino acid sequences of HDAgs between different HDV genotypes range from 30% to 38%, the significance of these high variations has not been clear. In this study, we addressed whether the functional properties of HDAg are affected between HDV Genotypes I and II. Using co-expression of two antigens in HUH-7 cells followed by specific antibody precipitation, HDAgs of different origins were found to interact without genotypic discrimination. Co-assembly of HDAg-S with HDAg-L (in the presence of HBV surface antigen) in virus-like particles showed that interaction strength between HDAgs varied among isolates. While examined the trans-activating ability of HDAg-S on HDV replication, we found that trans-activating efficiency of HDAg-S varies among isolates and genotypes. The inability of HDAg-S to support HDV replication could have been due to weak interaction between the HDV RNA and HDAg. The different HDAgs-RNA binding efficiency may partly explain that the broad spectrum of disease associated with HDV infection.
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~-9-~ EPIDEMIOLOGICAL FEATURES AND PREVENTION MEASURES OF HEPATITIS B AND C IN RISK AREA
THE COMMON FUNCTIONAL C(-159)T POLYMORPHISM OF THE LPS RECEPTOR CD14 DOES NOT INFLUENCE THE DISEASE OUTCOME IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION
Carolin Meiler 1, Arndt Hartmann 2, Marcus Muehlbauer 1, Rainer Wiest I , Juergen Schoelmerich 1, Claus Hellerbrand 1. 1Dept. oflnternal Medicine
L 2Dept. of Pathology, University of Regensburg, Germany Clinical and experimental data suggest that liver cell activation by gutderived endotoxins and other bacterial products is an important pathogenic factor for progression of chronic liver disease. Recently, a C to T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and increased risk of alcoholic liver damage. The aim of this study was to investigate the correlation of this polymorphism with the disease outcome and response to interferon therapy in patients with chronic hepatitis C infection (HepC). Methods: Liver biopsy was taken from 92 patients with HepC. Staging and grading were performed. 70 patients received treatment with IFN 4ribavirin. Genotyping was performed by restriction length polymorphism. Frequency of CD 14 genotypes was compared to 247 healthy controls. Results: Patients with HepC had comparable frequency of the C to T mutation as controls: 19/91 (20.9%) TT (controls: 22.3%), 49/91 (53.8%) CT (controls: 51.8%) and 23/91 (25.3%) CC (controls: 25.9%). Frequency of CD14 genotypes did not differ significantly in patients with different stages of fibrosis or inflammation and in virological responders and nonresponders.
Natalia Issaeva, lrina Feldblioum, Natalia Koza. Perm State Medical
Academy, Perm, Russia The aim of this investigation was to carry out epidemiologicai assessment of the prevalence rate and transmission routes of hepatitis B (HB) and C (HC) in risk area, and to determine current recommendations for their prevention. The study of the prevalence of HB and HC in 1994-2000 according to the official statistics was done in Penn region with population of 1 million. Anti-HBV and anti-HCV antibodies were tested by EIA in 612 injecting drug users (IDUs). In Penn region the prevalence of HB and HC was on a high level and stable (199.6-311.2 per 100 000 of the population). HB and HC age groups were between 12-29 years of age. In 2000 from 53.4% to 80.6% of reported cases of HB and HC among the age risk groups were associated with IDU. Introduction and the first experience of IDU occur as a rule at the age of 12 and 18, and very often 12 year old children are stable drug abusers. The prevalence of anti-HBV and anti-HCV in IDUs rose from 18.8% to 97%. The highest priority for prevention of HB received vaccination in infants, adolescents and others risk groups. Prevention measures of HC include monitoring of the spread of drug addiction, active detection of latent IDUs population, special protective programs for persons with high risk drug or sexual practices, professional and public education. HB and HC prevention in risk area have been developed on the basis of the current characteristics of their epidemiology.
CYTOKINE PROFILE IN HCV+ PATIENTS WITH AND WITHOUT CIRRHOSIS
Gabriela Gutierrez t, Socorro Cruz 2, Sara Sixtos 3, Teresa Ramirez 4, Concepcion Gutierrez 5, Graciela Castro 6, Ernesto Roldan 7, Florencia Vargas s, David Kershenobich9 . llnstituto Nacional De Ciencias
Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 21nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 31nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E; 4Instituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E ; 51nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; 61nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran ', Mexico D.E ; 71nstituto Nacional De Oencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.F.; Slnstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran', Mexico D.E; 91nstituto Nacional De Ciencias Medicas Y Nutricion 'Salvador Zubiran ', Mexico D.E, Mexico
Background: The infected peripheral mononuclear blood cells (PMBC)
223
Diskussion: The functional C(-159)T polymorphism of the CD14 gene does not seem to correlate with the degree of liver damage in patients with HepC - different from alcoholic liver disease. This may indicate that LPS mediated signal transduction is less important in this group of patients or may suggest that other mechanism for LPS recognition, such as toll-like receptors, are important in chronic HepC.
~-~
HEPATITIS DELTA ANTIGENS OLIGOMERIZE WITHOUT GENOTYPIC SPECIFICITY BUT VARY WITH TRANS-ACTIVATING EFFICIENCIES BETWEEN GENOTYPES I AND II HDV
Sheng-Chieh Hsu 1,2,3, Jaw-Ching Wu 2,3, Wan-Jr Syu I . 1Institutes of Microbiology and Immunology, National Yang-Ming University, Taipei; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei; 3Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, ROC
may be involved in the selection and persistence of the hepatitis C virus (HCV) genomic variants as well as triggering and maintaining liver fibrosis. Objective: Determine the expression and secretion of cytokines in HCV patients and cirrhotic HCV patients (C-HCV). Method: PMBC from 11 C-HCV and 15 HCV patients were obtained. Cells were cultured during 24 h. IL-lb, TNF-a, IL-8 and IFN-g secretion and expression were determined. RT-PCR for these cytokines was done in liver biopsies. Results: IL-lb secretion was similar in HCV and C-HCV (p = 0.002). IL-1 secretion in C-HCV correlate with IL-8 from HCV patients (p = 0.01). TNF-a secretion was similar in HCV and C-HCV (p -- 0.014). ILlb expression in liver biopsy was high in C-HCV and HCV patients (p = 0.021). There were no correlation between IL-8 and IFN-g. IL-8 secretion and expression in PMBC was elevated in both groups of patients. Conclusions: In chronic hepatitis C, IL-lb play a role in the immune response at injury by HCV. Also the activation of the immune response in hepatitis C was through TNFa and IL-lb. The HCV infection may activate a very specific immune response in the liver to allow chronic infection, which can lead to liver damage, hepatitis and cirrhosis. Thus, this cytokines may be useful in diagnosing and progression of Hepatitis C.
Hepatitis D virus (HDV) has different genotypes that vary in both nucleotides and the encoded delta antigen (HDAg). The small form of HDAg (HDAg-S) supports the viral RNA replication while the large form of HDAg (HDAg-L) is essential for virus assembly. Oligomerization and RNA binding activity of HDAgs are needed for HDV replication and virus particle assembly. Variations in amino acid sequences of HDAgs between different HDV genotypes range from 30% to 38%, the significance of these high variations has not been clear. In this study, we addressed whether the functional properties of HDAg are affected between HDV Genotypes I and II. Using co-expression of two antigens in HUH-7 cells followed by specific antibody precipitation, HDAgs of different origins were found to interact without genotypic discrimination. Co-assembly of HDAg-S with HDAg-L (in the presence of HBV surface antigen) in virus-like particles showed that interaction strength between HDAgs varied among isolates. While examined the trans-activating ability of HDAg-S on HDV replication, we found that trans-activating efficiency of HDAg-S varies among isolates and genotypes. The inability of HDAg-S to support HDV replication could have been due to weak interaction between the HDV RNA and HDAg. The different HDAgs-RNA binding efficiency may partly explain that the broad spectrum of disease associated with HDV infection.
~"]
~-9-~ EPIDEMIOLOGICAL FEATURES AND PREVENTION MEASURES OF HEPATITIS B AND C IN RISK AREA
THE COMMON FUNCTIONAL C(-159)T POLYMORPHISM OF THE LPS RECEPTOR CD14 DOES NOT INFLUENCE THE DISEASE OUTCOME IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION
Carolin Meiler 1, Arndt Hartmann 2, Marcus Muehlbauer 1, Rainer Wiest I , Juergen Schoelmerich 1, Claus Hellerbrand 1. 1Dept. oflnternal Medicine
L 2Dept. of Pathology, University of Regensburg, Germany Clinical and experimental data suggest that liver cell activation by gutderived endotoxins and other bacterial products is an important pathogenic factor for progression of chronic liver disease. Recently, a C to T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and increased risk of alcoholic liver damage. The aim of this study was to investigate the correlation of this polymorphism with the disease outcome and response to interferon therapy in patients with chronic hepatitis C infection (HepC). Methods: Liver biopsy was taken from 92 patients with HepC. Staging and grading were performed. 70 patients received treatment with IFN 4ribavirin. Genotyping was performed by restriction length polymorphism. Frequency of CD 14 genotypes was compared to 247 healthy controls. Results: Patients with HepC had comparable frequency of the C to T mutation as controls: 19/91 (20.9%) TT (controls: 22.3%), 49/91 (53.8%) CT (controls: 51.8%) and 23/91 (25.3%) CC (controls: 25.9%). Frequency of CD14 genotypes did not differ significantly in patients with different stages of fibrosis or inflammation and in virological responders and nonresponders.
Natalia Issaeva, lrina Feldblioum, Natalia Koza. Perm State Medical
Academy, Perm, Russia The aim of this investigation was to carry out epidemiologicai assessment of the prevalence rate and transmission routes of hepatitis B (HB) and C (HC) in risk area, and to determine current recommendations for their prevention. The study of the prevalence of HB and HC in 1994-2000 according to the official statistics was done in Penn region with population of 1 million. Anti-HBV and anti-HCV antibodies were tested by EIA in 612 injecting drug users (IDUs). In Penn region the prevalence of HB and HC was on a high level and stable (199.6-311.2 per 100 000 of the population). HB and HC age groups were between 12-29 years of age. In 2000 from 53.4% to 80.6% of reported cases of HB and HC among the age risk groups were associated with IDU. Introduction and the first experience of IDU occur as a rule at the age of 12 and 18, and very often 12 year old children are stable drug abusers. The prevalence of anti-HBV and anti-HCV in IDUs rose from 18.8% to 97%. The highest priority for prevention of HB received vaccination in infants, adolescents and others risk groups. Prevention measures of HC include monitoring of the spread of drug addiction, active detection of latent IDUs population, special protective programs for persons with high risk drug or sexual practices, professional and public education. HB and HC prevention in risk area have been developed on the basis of the current characteristics of their epidemiology.