- Email: [email protected]
351 THE CHANGES OF INTRAHEPATIC CCCDNA DURING ENTECAVIR OR ADEFOVIR DIPIVOXIL TREATMENT FOR CHRONIC HEPATITIS B PATIENTS
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Poster Session − Thursday, April 23
54.82 kcal/mol, 357.58 kcal/mol, and 650.83 kcal/mol for the wildtype NS4B homodimer, the wildtype/mutant heterodimer, and the mutant heterodimer, respectively. Conclusions: We have shown expression and protein-protein interaction of HCV NS4B molecules. This interaction was disturbed by alteration of a basic leucine zipper motif. Our in-vitro data were complemented by insilico structure modelling of the identified NS4B homodimer. Calculation of interaction energies were in concordance with co-immunoprecipitation studies.
05d: VIRAL HEPATITIS − d) HEPATITIS B − CLINICAL (EXCEPT THERAPY)
349 INCIDENCE OF APBEC3B GENE DELETION IN JAPANESE POPULATION AND SIGNIFICANCE IN HEPATITIS B VIRUS INFECTION AND G TO A HYPERMUTATION OF THE VIRUS GENOME H. Abe1,2 , H. Ochi1 , T. Maekawa2 , M. Tsuge1 , M. Imamura1 , N. Hiraga1 , S. Takahashi1 , Y. Fujimoto1 , K. Chayama1,2 . 1 Department of Gastroenterology and Metabolism, Hiroshima University, 2 Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan E-mail: [email protected] Background and Aims: APOBEC proteins are known to play a role in the innate anti-viral immunity. A 29.5-kb deletion polymorphism of human APOBEC3B gene has been reported. We investigated the incidence and significance of the APOBEC3B gene deletion in chronic hepatitis B virus (HBV) infection and viral genomic hypermutation in Japanese patients. Methods: We genotyped 377 Japanese individuals with chronic HBV infection for the APOBEC3B gene deletion by PCR using primers designed to specifically detect deleted and non-deleted alleles (Kidd J et al. PLos genetics 2007). Clinical parameters from all 377 patients and histological findings obtained from 180 of them were analyzed. G to A hypermutation of HBV genomes was detected by amplification of HBV genomic DNA by 3D PCR, cloning and nucleotide sequencing. Results: The frequency of the deletion allele was 47.0%. There is no significant association between biochemical and hematological findings and the genotypes except that the patients with high ALT levels were frequently seen in individuals with deletion homo genotype. However, histologically advanced liver diseases are not infrequent in patients with insertion homo and hetero genotypes. To examine the significance of the APOBEC3B allele deletion on G to A hypermutation, we examined serum samples obtained from patients with deletion and insertion homo genotype. Up to 81% of G residues of HBV genome were substituted to A at most in the both group of the patients. Nucleotide sequence context analysis showed that G residues one nucleotide 3’ from A residue were most frequently mutated in deletion homo genotype, but there was no statistically significant difference. Conclusions: Although there is 8.5% APOBEC3B homologous deletion population in Japanese, our results suggested that the absence of APOBEC3B gene does not affect the incidence of chronic HBV infection. The absence of the gene also does not result in apparent impaired clinical course in chronic HBV infected patients although ALT levels tended to be high in individuals with deletion homo genotype. Many HBV clones with G to A hypermutation were detected in the absence of APOBEC3B. These results suggest that other APOBEC protein(s) compensate the deletion of the APOBEC3B.
350 CLINICAL FACTORS PREDICTING ADVANCED LIVER FIBROSIS IN HEPATITIS B E ANTIGEN POSITIVE CHRONIC HEPATITIS B H.L. Chan, G.L. Wong, P.C. Choi, A.W. Chan, A.M. Chim, K.K. Yiu, H.Y. Chan, V.W. Wong. The Chinese University of Hong Kong, Hong Kong, Hong Kong S.A.R. E-mail: [email protected] Background and Aims: Among patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B, it is sometimes difficult to differentiate immune tolerance and advanced liver fibrosis particularly when alanine aminotransferase (ALT) is normal. The timing of liver biopsy is controversial when anti-viral treatment is considered. We aimed to determine the clinical factors that could predict advanced liver fibrosis in HBeAg-positive chronic hepatitis B. Methods: We prospectively recruited treatment-naive HBeAg-positive patients from a territory-wide referral for liver stiffness measurement (LSM) by transient elastography. Other causes of liver diseases were excluded. Based on our previous histologic validation, insignificant and advanced fibrosis was defined as LSM 6.0 kPa and >9.0 kPa when ALT was normal and 7.5 kPa and >12.0 kPa when ALT was elevated (up to 5× upper limit of normal [ULN]), respectively. Results: 453 HBeAg-positive patients were studied. Among 74 patients who also had liver biopsy (at least 15 mm long with 6 portal tracts), the LSM cut-offs had 90% sensitivity to exclude and 95% specificity to confirm F3−4 fibrosis. Based on LSM, 216 (48%) patients had insignificant fibrosis and 102 (30%) patients had advanced fibrosis. On multivariate analysis, age and ALT, but not male gender, obesity or hepatitis B virus DNA, were independently associated with LSM. On receiver operating characteristics curve analysis, patients aged older than 35 had the highest specificity (91%) for advanced fibrosis. The risk of advanced fibrosis started to increase when ALT was higher than 0.5xULN (odds ratio 5.0, 95% CI 1.9−13.1, P < 0.001). Among the 47 patients aged 35 with ALT 0.5xULN, 39 (83%) had LSM suggestive of insignificant fibrosis and 1 (2%) had advanced fibrosis. Among the 217 patients aged >35 with ALT > 0.5×ULN, 61 (28%) had LSM suggestive of insignificant fibrosis and 80 (37%) had advanced fibrosis. The number of patients needed to be biopsied to detect one case of advanced fibrosis was 47 for patients aged 35 years and ALT 0.5×ULN but was only 3 for patients aged >35 years and ALT > 0.5×ULN. Conclusions: Risk of advanced liver fibrosis increased in HBeAg-positive patients aged over 35 years with ALT > 0.5×ULN. 351 THE CHANGES OF INTRAHEPATIC CCCDNA DURING ENTECAVIR OR ADEFOVIR DIPIVOXIL TREATMENT FOR CHRONIC HEPATITIS B PATIENTS P.-N. Cheng1 , I.-C. Wu1 , K.-C. Young2 , T.-T. Chang3 . 1 Department of Internal Medicine, National Cheng Kung University Hospital, 2 Department of Laboratory Science and Biotechnology, 3 Department of Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan E-mail: [email protected] Entecavir (ETV) and adefovir dipivoxil (ADV) are effective in treatment of chronic hepatitis B. Their efficacy exerted in hepatocyte covalently closed circular DNA (cccDNA) needed to determined. Forty nine chronic hepatitis B patients were included and subdivided into three groups of ETV group (13 patients), ADV group (22 patients), and placebo group (14 patients) based on age and gender. All of them were treated for 48 weeks. Serum HBV DNA levels, and liver total intrahepatic HBV DNA levels and hepatocyte cccDNA levels were measured for each patient at the timepoints of baseline and after 48 weeks of treatment. The baseline median total intrahepatic HBV DNA per hepatocyte was 205.42 copies and median cccDNA was 0.23 copies. After 48-week treatment, ETV induced a significant reduction in both serum HBV DNA (6.21 log 10 vs. 4.27 log 10 copies/mL, P < 0.001) and total intrahepatic
05d: VIRAL HEPATITIS − d) HEPATITIS B − CLINICAL (EXCEPT THERAPY) HBV DNA levels (1.69 log 10 vs. 1.23 log 10 copies/cell, P = 0.049) than ADV. The level of cccDNA in ETV group had greater, but not significant, reduction than ADV group (0.25 log 10 vs. 0.09 log 10 copies/cell). The proportions of reduction in serum HBV DNA, total intrahepatic HBV DNA, cccDNA resulted from drug treatment were 99.5%, 92.7%, 17.3% for ADV and 99.9%, 97.0%, 41.4% for ETV, respectively. Median replication activity (ratio of replicative intermediates of HBV and cccDNA in hepatocyte) decreased significantly after 48-week ADV (380 at baseline to 64 at week 48, P < 0.001) and ETV treatment (1942 at baseline to 71 at week 48, P < 0.001). ETV exerted stronger suppression effect in serum HBV DNA, total intrahepatic HBV DNA than ADV. A 48-week of ETV or ADV treatment was not enough to effectively suppress hepatocyte cccDNA. 352 INTERFERON-g INDUCIBLE PROTEIN-10 (IP-10) IS A PREDICTOR OF OUTCOME DURING THE ACUTE PHASE OF HCV INFECTION S. Chokshi1 , A. Guobuzaite2 , A. Riva1 , A. Evans1 , S. Phillips1 , A. Ambrozaitis2 , N. Naoumov1 . 1 Department of Medicine, Institute of Hepatology, University College London, London, UK; 2 Department of Infectious Diseases, Vilnius University, Vilnius, Lithuania E-mail: [email protected] Background: The underlying mechanisms by which HCV evades immuneclearance and establishes persistence are not fully understood. Early interactions between the virus and host immune responses are critical in determining the outcome of HCV infection. In patients with chronic hepatitis C, the proinflammatory chemokine IP-10 is involved in recruiting activated T-lymphocytes into the liver. Blockade of IP-10 in murine models reduces lymphocyte recruitment into the liver and the severity of liver disease without affecting the antiviral potential of antigen-specific T-lymphocytes. Pre-treatment IP-10 levels are also predictive of a rapid and sustained viral response in HCV patients treated with pegylated interferon-alpha-2a and ribavirin.The aim of this study was to investigate plasma cytokine levels in patients with acute HCV and assess their impact on outcome of infection. Patients and Methods: We recruited 18 patients with acute HCV infection with the following criteria: ALT > 10×ULN; exposure to HCV within the past 4 months and seropositivity for HCV-RNA. Samples were collected monthly for 6 months following presentation.HCV-RNA levels were determined by qPCR and a panel of 17 serum cytokines, including IP-10, were quantified by Cytokine Bead Array® (BD Biosciences). Additionally, we enumerated virus-specific T-cell responses by IFNg/IL-10 Elispot assays(BD Biosciences). Results: Seven patients resolved HCV spontaneously, while 11/18(61%) developed chronic infection. Serum IP-10 levels differed significantly between resolved and chronic patients(p = 0.006) with markedly lower levels of IP-10 observed in resolvers at baseline, month(M)1 and 3 (p = 0.023, p = 0.03, p = 0.045, respectively. IP-10 levels at presentation, within the chronic patients, directly correlated with serum HCV-RNA(r = 0.709, p = 0.007). Within resolved patients a significant decrease was also observed between presentation and M1(p = 0.003) and between M1 and M3 (p = 0.014).A temporal correlation was also observed between IP-10 level and ALT in resolved patients(r = 0.998 p = 0.001). Furthermore, in resolved patients IP-10 levels directly correlated with serum IFNglevels at M1, M3 and M6 (p = 0.016 r = 0.797, p = 0.026 r = 0.806, p = 0.049 r = 0.732, respectively). Conclusions: Plasma IP-10 levels during the acute phase of HCV infection are significantly lower in patients who subsequently resolve infection and therefore may be used to predict disease outcome. Furthermore, elevated IP-10 is associated with and may contribute to the persistence of HCV infection.
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353 HBV SEROLOGICAL PATTERNS IN PUBLIC HOSPITALS FROM A BIG CITY OF SOUTHERN FRANCE OVER A SEVEN-YEAR PERIOD (1998–2004) P. Colson1,2 , H. Richet3 , C. Tamalet3 . 1 F´ed´eration de Microbiologie Clinique, Hˆopital Timone, AP-HM, 2 URMITE CNRS-IRD 6236, Facult´e de Pharmacie, Universit´e de la M´edit´erran´ee, 3 Hˆopital Timone, AP-HM, Marseille, France E-mail: [email protected] Background and Aims: Hepatitis B remains a public health concern in France with an estimated prevalence of HBsAg-carriage of 0.65% within the general population, knowledge of this serological status in around half of infected people, and a persisting distrust of an important part of the French population against the HBV vaccine. We aimed at assessing the proportion of HBsAg carriers, HBsAg-negative/anti-HBc antibodiespositive individuals, and individuals with isolated anti-HBs antibodies indicating vaccine immunization among patients tested for their HBV serological status in public hospitals of Marseilles, a big city of southern France. Methods: We undertook a 7-year retrospective survey of HBV serological status in all patients who were newly-tested in Marseilles public hospitals between 1998–2004 (Axsym Abbott assays). HBsAg-carriage: detection of HBsAg and anti-HBc antibodies. Past-infection profile: presence of antiHBc antibodies and anti-HBs antibodies (>10 mIU/ml) and/or anti-HBe antibodies with HBsAg-negativity. Vaccine immunization profile: anti-HBs positivity (>10 mIU/ml) in the absence of anti-HBc antibodies. Statistical analysis was performed using Epi Info 6. Results: HBV serological status of 78,603 newly-tested patients were analyzed. The proportion of HbsAg-carriers in newly-tested patients during the whole study period was 1.87%, and 2.21% among individuals in the 18−45 years age group. Furthermore, the proportion of individuals in the whole population with a serological profile indicating past-infection was 12.4%, rising significantly from 1.8% in people <18 years of age to 9.9% in the 18−45 years age group (P < 10−6 ; RR = 0.18, 95% CI: 0.15−0.23). HBV serology indicating vaccine immunization was detected in 33.6% of all individuals, 29.5% of newborns (<18 months of age), and only reached 47.1% in young adults in the 18−45 years age group. Moreover, it significantly decreased from 57.0% to 44.3% (P < 10−5 ) from 1998 to 2004 in children and adolescents between 18 months-18 years of age. Conclusions: Our data highlight a high rate of HBV chronic carriers, of anti-HBc-positive patients, and a low rate of patients with serological profile indicating HBV vaccination among individuals tested in public hospitals of a big city of southern France. We found in this population an absence of progress towards the universal HBV immunization proned by the WHO. 354 PREVALENCE OF SIGNIFICANT FIBROSIS AND CORRELATIONS BETWEEN HISTOLOGICAL INFLAMMATION AND FIBROSIS SCORES AND SERUM HEPATITIS B (HBV) DNA LEVELS IN CHRONIC HEPATITIS B C. Croagh1 , S. Bell1 , Y. Kong1 , R. Chen1 , J. Slavin1 , S. Locarnini2 , P. Desmond1 . 1 Department of Gastroenterology, St Vincent’s Hospital, 2 Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia E-mail: [email protected] Introduction: Hepatitis B (HBV) DNA levels have been shown to correlate with the outcome of cirrhosis, with higher viral loads being associated with an increased risk of developing cirrhosis. Aims: To evaluate the prevalence of significant fibrosis and to examine the relationship between serum HBV DNA and Alanine aminotransferase (ALT) levels and histological liver inflammation and fibrosis scores in Chronic Hepatitis B (CHB) patients. Methods: A review of the St Vincent’s Hospital HBV database was performed to identify patients with CHB who had undergone a liver biopsy.
Poster Session − Thursday, April 23
54.82 kcal/mol, 357.58 kcal/mol, and 650.83 kcal/mol for the wildtype NS4B homodimer, the wildtype/mutant heterodimer, and the mutant heterodimer, respectively. Conclusions: We have shown expression and protein-protein interaction of HCV NS4B molecules. This interaction was disturbed by alteration of a basic leucine zipper motif. Our in-vitro data were complemented by insilico structure modelling of the identified NS4B homodimer. Calculation of interaction energies were in concordance with co-immunoprecipitation studies.
05d: VIRAL HEPATITIS − d) HEPATITIS B − CLINICAL (EXCEPT THERAPY)
349 INCIDENCE OF APBEC3B GENE DELETION IN JAPANESE POPULATION AND SIGNIFICANCE IN HEPATITIS B VIRUS INFECTION AND G TO A HYPERMUTATION OF THE VIRUS GENOME H. Abe1,2 , H. Ochi1 , T. Maekawa2 , M. Tsuge1 , M. Imamura1 , N. Hiraga1 , S. Takahashi1 , Y. Fujimoto1 , K. Chayama1,2 . 1 Department of Gastroenterology and Metabolism, Hiroshima University, 2 Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan E-mail: [email protected] Background and Aims: APOBEC proteins are known to play a role in the innate anti-viral immunity. A 29.5-kb deletion polymorphism of human APOBEC3B gene has been reported. We investigated the incidence and significance of the APOBEC3B gene deletion in chronic hepatitis B virus (HBV) infection and viral genomic hypermutation in Japanese patients. Methods: We genotyped 377 Japanese individuals with chronic HBV infection for the APOBEC3B gene deletion by PCR using primers designed to specifically detect deleted and non-deleted alleles (Kidd J et al. PLos genetics 2007). Clinical parameters from all 377 patients and histological findings obtained from 180 of them were analyzed. G to A hypermutation of HBV genomes was detected by amplification of HBV genomic DNA by 3D PCR, cloning and nucleotide sequencing. Results: The frequency of the deletion allele was 47.0%. There is no significant association between biochemical and hematological findings and the genotypes except that the patients with high ALT levels were frequently seen in individuals with deletion homo genotype. However, histologically advanced liver diseases are not infrequent in patients with insertion homo and hetero genotypes. To examine the significance of the APOBEC3B allele deletion on G to A hypermutation, we examined serum samples obtained from patients with deletion and insertion homo genotype. Up to 81% of G residues of HBV genome were substituted to A at most in the both group of the patients. Nucleotide sequence context analysis showed that G residues one nucleotide 3’ from A residue were most frequently mutated in deletion homo genotype, but there was no statistically significant difference. Conclusions: Although there is 8.5% APOBEC3B homologous deletion population in Japanese, our results suggested that the absence of APOBEC3B gene does not affect the incidence of chronic HBV infection. The absence of the gene also does not result in apparent impaired clinical course in chronic HBV infected patients although ALT levels tended to be high in individuals with deletion homo genotype. Many HBV clones with G to A hypermutation were detected in the absence of APOBEC3B. These results suggest that other APOBEC protein(s) compensate the deletion of the APOBEC3B.
350 CLINICAL FACTORS PREDICTING ADVANCED LIVER FIBROSIS IN HEPATITIS B E ANTIGEN POSITIVE CHRONIC HEPATITIS B H.L. Chan, G.L. Wong, P.C. Choi, A.W. Chan, A.M. Chim, K.K. Yiu, H.Y. Chan, V.W. Wong. The Chinese University of Hong Kong, Hong Kong, Hong Kong S.A.R. E-mail: [email protected] Background and Aims: Among patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B, it is sometimes difficult to differentiate immune tolerance and advanced liver fibrosis particularly when alanine aminotransferase (ALT) is normal. The timing of liver biopsy is controversial when anti-viral treatment is considered. We aimed to determine the clinical factors that could predict advanced liver fibrosis in HBeAg-positive chronic hepatitis B. Methods: We prospectively recruited treatment-naive HBeAg-positive patients from a territory-wide referral for liver stiffness measurement (LSM) by transient elastography. Other causes of liver diseases were excluded. Based on our previous histologic validation, insignificant and advanced fibrosis was defined as LSM 6.0 kPa and >9.0 kPa when ALT was normal and 7.5 kPa and >12.0 kPa when ALT was elevated (up to 5× upper limit of normal [ULN]), respectively. Results: 453 HBeAg-positive patients were studied. Among 74 patients who also had liver biopsy (at least 15 mm long with 6 portal tracts), the LSM cut-offs had 90% sensitivity to exclude and 95% specificity to confirm F3−4 fibrosis. Based on LSM, 216 (48%) patients had insignificant fibrosis and 102 (30%) patients had advanced fibrosis. On multivariate analysis, age and ALT, but not male gender, obesity or hepatitis B virus DNA, were independently associated with LSM. On receiver operating characteristics curve analysis, patients aged older than 35 had the highest specificity (91%) for advanced fibrosis. The risk of advanced fibrosis started to increase when ALT was higher than 0.5xULN (odds ratio 5.0, 95% CI 1.9−13.1, P < 0.001). Among the 47 patients aged 35 with ALT 0.5xULN, 39 (83%) had LSM suggestive of insignificant fibrosis and 1 (2%) had advanced fibrosis. Among the 217 patients aged >35 with ALT > 0.5×ULN, 61 (28%) had LSM suggestive of insignificant fibrosis and 80 (37%) had advanced fibrosis. The number of patients needed to be biopsied to detect one case of advanced fibrosis was 47 for patients aged 35 years and ALT 0.5×ULN but was only 3 for patients aged >35 years and ALT > 0.5×ULN. Conclusions: Risk of advanced liver fibrosis increased in HBeAg-positive patients aged over 35 years with ALT > 0.5×ULN. 351 THE CHANGES OF INTRAHEPATIC CCCDNA DURING ENTECAVIR OR ADEFOVIR DIPIVOXIL TREATMENT FOR CHRONIC HEPATITIS B PATIENTS P.-N. Cheng1 , I.-C. Wu1 , K.-C. Young2 , T.-T. Chang3 . 1 Department of Internal Medicine, National Cheng Kung University Hospital, 2 Department of Laboratory Science and Biotechnology, 3 Department of Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan E-mail: [email protected] Entecavir (ETV) and adefovir dipivoxil (ADV) are effective in treatment of chronic hepatitis B. Their efficacy exerted in hepatocyte covalently closed circular DNA (cccDNA) needed to determined. Forty nine chronic hepatitis B patients were included and subdivided into three groups of ETV group (13 patients), ADV group (22 patients), and placebo group (14 patients) based on age and gender. All of them were treated for 48 weeks. Serum HBV DNA levels, and liver total intrahepatic HBV DNA levels and hepatocyte cccDNA levels were measured for each patient at the timepoints of baseline and after 48 weeks of treatment. The baseline median total intrahepatic HBV DNA per hepatocyte was 205.42 copies and median cccDNA was 0.23 copies. After 48-week treatment, ETV induced a significant reduction in both serum HBV DNA (6.21 log 10 vs. 4.27 log 10 copies/mL, P < 0.001) and total intrahepatic
05d: VIRAL HEPATITIS − d) HEPATITIS B − CLINICAL (EXCEPT THERAPY) HBV DNA levels (1.69 log 10 vs. 1.23 log 10 copies/cell, P = 0.049) than ADV. The level of cccDNA in ETV group had greater, but not significant, reduction than ADV group (0.25 log 10 vs. 0.09 log 10 copies/cell). The proportions of reduction in serum HBV DNA, total intrahepatic HBV DNA, cccDNA resulted from drug treatment were 99.5%, 92.7%, 17.3% for ADV and 99.9%, 97.0%, 41.4% for ETV, respectively. Median replication activity (ratio of replicative intermediates of HBV and cccDNA in hepatocyte) decreased significantly after 48-week ADV (380 at baseline to 64 at week 48, P < 0.001) and ETV treatment (1942 at baseline to 71 at week 48, P < 0.001). ETV exerted stronger suppression effect in serum HBV DNA, total intrahepatic HBV DNA than ADV. A 48-week of ETV or ADV treatment was not enough to effectively suppress hepatocyte cccDNA. 352 INTERFERON-g INDUCIBLE PROTEIN-10 (IP-10) IS A PREDICTOR OF OUTCOME DURING THE ACUTE PHASE OF HCV INFECTION S. Chokshi1 , A. Guobuzaite2 , A. Riva1 , A. Evans1 , S. Phillips1 , A. Ambrozaitis2 , N. Naoumov1 . 1 Department of Medicine, Institute of Hepatology, University College London, London, UK; 2 Department of Infectious Diseases, Vilnius University, Vilnius, Lithuania E-mail: [email protected] Background: The underlying mechanisms by which HCV evades immuneclearance and establishes persistence are not fully understood. Early interactions between the virus and host immune responses are critical in determining the outcome of HCV infection. In patients with chronic hepatitis C, the proinflammatory chemokine IP-10 is involved in recruiting activated T-lymphocytes into the liver. Blockade of IP-10 in murine models reduces lymphocyte recruitment into the liver and the severity of liver disease without affecting the antiviral potential of antigen-specific T-lymphocytes. Pre-treatment IP-10 levels are also predictive of a rapid and sustained viral response in HCV patients treated with pegylated interferon-alpha-2a and ribavirin.The aim of this study was to investigate plasma cytokine levels in patients with acute HCV and assess their impact on outcome of infection. Patients and Methods: We recruited 18 patients with acute HCV infection with the following criteria: ALT > 10×ULN; exposure to HCV within the past 4 months and seropositivity for HCV-RNA. Samples were collected monthly for 6 months following presentation.HCV-RNA levels were determined by qPCR and a panel of 17 serum cytokines, including IP-10, were quantified by Cytokine Bead Array® (BD Biosciences). Additionally, we enumerated virus-specific T-cell responses by IFNg/IL-10 Elispot assays(BD Biosciences). Results: Seven patients resolved HCV spontaneously, while 11/18(61%) developed chronic infection. Serum IP-10 levels differed significantly between resolved and chronic patients(p = 0.006) with markedly lower levels of IP-10 observed in resolvers at baseline, month(M)1 and 3 (p = 0.023, p = 0.03, p = 0.045, respectively. IP-10 levels at presentation, within the chronic patients, directly correlated with serum HCV-RNA(r = 0.709, p = 0.007). Within resolved patients a significant decrease was also observed between presentation and M1(p = 0.003) and between M1 and M3 (p = 0.014).A temporal correlation was also observed between IP-10 level and ALT in resolved patients(r = 0.998 p = 0.001). Furthermore, in resolved patients IP-10 levels directly correlated with serum IFNglevels at M1, M3 and M6 (p = 0.016 r = 0.797, p = 0.026 r = 0.806, p = 0.049 r = 0.732, respectively). Conclusions: Plasma IP-10 levels during the acute phase of HCV infection are significantly lower in patients who subsequently resolve infection and therefore may be used to predict disease outcome. Furthermore, elevated IP-10 is associated with and may contribute to the persistence of HCV infection.
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353 HBV SEROLOGICAL PATTERNS IN PUBLIC HOSPITALS FROM A BIG CITY OF SOUTHERN FRANCE OVER A SEVEN-YEAR PERIOD (1998–2004) P. Colson1,2 , H. Richet3 , C. Tamalet3 . 1 F´ed´eration de Microbiologie Clinique, Hˆopital Timone, AP-HM, 2 URMITE CNRS-IRD 6236, Facult´e de Pharmacie, Universit´e de la M´edit´erran´ee, 3 Hˆopital Timone, AP-HM, Marseille, France E-mail: [email protected] Background and Aims: Hepatitis B remains a public health concern in France with an estimated prevalence of HBsAg-carriage of 0.65% within the general population, knowledge of this serological status in around half of infected people, and a persisting distrust of an important part of the French population against the HBV vaccine. We aimed at assessing the proportion of HBsAg carriers, HBsAg-negative/anti-HBc antibodiespositive individuals, and individuals with isolated anti-HBs antibodies indicating vaccine immunization among patients tested for their HBV serological status in public hospitals of Marseilles, a big city of southern France. Methods: We undertook a 7-year retrospective survey of HBV serological status in all patients who were newly-tested in Marseilles public hospitals between 1998–2004 (Axsym Abbott assays). HBsAg-carriage: detection of HBsAg and anti-HBc antibodies. Past-infection profile: presence of antiHBc antibodies and anti-HBs antibodies (>10 mIU/ml) and/or anti-HBe antibodies with HBsAg-negativity. Vaccine immunization profile: anti-HBs positivity (>10 mIU/ml) in the absence of anti-HBc antibodies. Statistical analysis was performed using Epi Info 6. Results: HBV serological status of 78,603 newly-tested patients were analyzed. The proportion of HbsAg-carriers in newly-tested patients during the whole study period was 1.87%, and 2.21% among individuals in the 18−45 years age group. Furthermore, the proportion of individuals in the whole population with a serological profile indicating past-infection was 12.4%, rising significantly from 1.8% in people <18 years of age to 9.9% in the 18−45 years age group (P < 10−6 ; RR = 0.18, 95% CI: 0.15−0.23). HBV serology indicating vaccine immunization was detected in 33.6% of all individuals, 29.5% of newborns (<18 months of age), and only reached 47.1% in young adults in the 18−45 years age group. Moreover, it significantly decreased from 57.0% to 44.3% (P < 10−5 ) from 1998 to 2004 in children and adolescents between 18 months-18 years of age. Conclusions: Our data highlight a high rate of HBV chronic carriers, of anti-HBc-positive patients, and a low rate of patients with serological profile indicating HBV vaccination among individuals tested in public hospitals of a big city of southern France. We found in this population an absence of progress towards the universal HBV immunization proned by the WHO. 354 PREVALENCE OF SIGNIFICANT FIBROSIS AND CORRELATIONS BETWEEN HISTOLOGICAL INFLAMMATION AND FIBROSIS SCORES AND SERUM HEPATITIS B (HBV) DNA LEVELS IN CHRONIC HEPATITIS B C. Croagh1 , S. Bell1 , Y. Kong1 , R. Chen1 , J. Slavin1 , S. Locarnini2 , P. Desmond1 . 1 Department of Gastroenterology, St Vincent’s Hospital, 2 Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia E-mail: [email protected] Introduction: Hepatitis B (HBV) DNA levels have been shown to correlate with the outcome of cirrhosis, with higher viral loads being associated with an increased risk of developing cirrhosis. Aims: To evaluate the prevalence of significant fibrosis and to examine the relationship between serum HBV DNA and Alanine aminotransferase (ALT) levels and histological liver inflammation and fibrosis scores in Chronic Hepatitis B (CHB) patients. Methods: A review of the St Vincent’s Hospital HBV database was performed to identify patients with CHB who had undergone a liver biopsy.