- Email: [email protected]
484 HEPATITIS B CORE-RELATED ANTIGEN AND QUANTITATIVE HEPATITIS B SURFACE ANTIGEN LEVELS IN JAPANESE PATIENTS WITH CHRONIC HEPATITIS B AFTER EXTENDED NUCLEOSIDE ANALOGUES TREATMENT
POSTERS in approximately 25% of inactive carriers and is associated with increased risk of moderate fibrosis, particularly in cases with HBVDNA >2000 IU/mL. 482 VERTICAL TRANSMISSION OF HEPATITIS B VIRUS (HBV) DUE TO IMMUNIZATION FAILURE: A UNITED STATES (US) POPULATION STUDY A. Pressman1,2 , C. Lin2 , L. De Leon2 , T. Park2 , S. Degli Esposti1,3,4 . 1 Women’s Medicine Collaborative at Lifespan, 2 Warren Alpert School of Medicine at Brown University, 3 Rhode Island Department of Health, 4 Women and Infants Hospital, Providence, RI, USA E-mail: [email protected] Background: HBV infections in the US have sharply declined, however immigrant populations represent a reservoir of disease. Immunization failures ranging 5–25% have been suggested by data from Asian countries and initiate the debate about antiviral therapy in pregnancy. Epidemiology of HBV infection in pregnancy within the US remains unknown. We aim to characterize the population of HBs antigen positive (HBsAg+) pregnant women in Rhode Island (RI) and to assess the rate of vertical transmission and true immuno-prophylaxis failure. Methods: The population study included all women giving birth in the state of Rhode Island and their offspring born between the years 2003 and 2009. Analysis included the cohort of HBsAg+ mothers identified pre-delivery by the RI Perinatal Hepatitis Program and followed prospectively. Data was extracted retrospectively from charts and State databases. Results: 82,105 infants were born in RI during the study period. 373 infants were born to HBsAg+ mothers. Mean maternal age at delivery was 29.2 years. Region of origin of HBsAg+ mothers was West Africa (44%), East Asia (4.8%), Southeast Asia (27.8%), Caribbean (11.3%), USA (7.6%) and less than 2% each from East Africa, Middle East, Europe, South America, Central America. Of those with viral load measurements, median HBV viral load was 544.5 copies/mL and 435 copies/mL in the subset of African born women. Only 15.2% of those with viral load data had HBV levels >1×108 copies/mL. 320 mother/infant pairs were included in analysis. 5 infants were HBsAg + at 9 months of age. Rate of vertical transmission was 1.6% [95% CI (0.5–3.6)]. Age, race and deviation from vaccination protocol did not appear to influence transmission. Only 2 of the 5 transmissions had viral load data, both with maternal HBV viral loads >1×108 copies/mL. Conclusions: This is the first US population study on Hepatitis B in pregnant patients in the US. African born women represent the majority among the HBV infected mothers in RI. Immunization failure is rare and may be because African born women appear to have lower viral loads. Current data obtained in prevalent Asian populations need to be applied with caution given possible variations of race and ethnicity. 483 ONE-STEP REAL-TIME REVERSE TRANSCRIPTION-PCR ASSAY FOR UNIVERSAL QUANTIFICATION OF HEPATITIS DELTA VIRUS FROM CLINICAL SAMPLES IN THE PRESENCE OF A HETEROLOGOUS INTERNAL CONTROL RNA C. Scholtes1,2,3 , V. Icard1 , M. Valiollahpour-Amiri4 , P. ChevallierQueyron1,2 , F. Zoulim2,4,5 , P. Deny ´ 5,6 , P. Andre´ 1,2,3 . 1 Laboratoire de Virologie, Hospices Civils de Lyon, Hˆ opital de la Croix Rousse, 2 Universit´e de Lyon, 3 Inserm U851, 4 H´epato-Gastroent´erologie, Hospices Civils de Lyon, Hˆ opital de la Croix Rousse, 5 CRCL, INSERM 6 1052-CNRS 5286, Lyon, Laboratoire Associ´e au CNR des H´epatites B, C et Delta, Hˆ opital Avicenne, Universit´e Paris 13, Paris, France E-mail: [email protected] Background and Aims: Patients with hepatitis D co-infection have a more severe liver disease with rapid progression to cirrhosis and S190
hepatic decompensation than hepatitis B monoinfected patients. Treatment relies on pegylated interferon but this therapy leads to viral clearance in only 28% of cases. Knowledge of the viral load may provide important information for patients’ follow up. Notably, it should be useful to monitor response to current and future antiviral therapies. However no commercial reference assay including automated nucleic acid extraction and internal control (IC) is currently available for HDV-RNA quantification and in-house assays are not yet standardized. Furthermore, HDV has a high genetic diversity, eight genotypes being described; this represents a challenge for full spectrum quantitative reverse transcription (qRT)PCR. Indeed, the majority of the available assays accurately quantify only genotype 1 isolates. Methods: In this study, the development of the first duplex (including IC) one-step real-time RT-PCR assay for detection and quantification of HDV is presented. Primers and probes binding to conserved regions of the HDV antigen were designed. Tenfold dilutions series of in-vitro-transcribed HDV1 RNA were used as the standard for quantification. A commercial heterologous encapsulated-RNA was used as IC for both RNA extraction and RT-PCR. Results: The duplex qRT-PCR for HDV had an efficiency of 0.97, a regression squared value of 0.999, and a sensitivity of approximately 30 copies per reaction mixture when in vitro-transcribed RNA was used as the template. The linearity of this assay ranged from 500 to 1.7×1011 copies/mL. The repeatability (approx. 15%), and the reproducibility (range 7.4%-21.9%) were comparable to commercial HCV and HIV assays. The presence of the IC did not affect amplification of HDV RNA compared to single assay. Synthetic templates and clinical samples from different geographical origins belonging to different genotypes were successfully detected and quantified. Conclusions: We described here the first automated one-step RTPCR assay with IC for universal quantification of HDV RNA. The wide dynamic range is necessary to quantify viral RNA from clinical samples that can reach more than 1010 copies/mL. This high sensitivity and specificity assay can be easily used for routine diagnostics. 484 HEPATITIS B CORE-RELATED ANTIGEN AND QUANTITATIVE HEPATITIS B SURFACE ANTIGEN LEVELS IN JAPANESE PATIENTS WITH CHRONIC HEPATITIS B AFTER EXTENDED NUCLEOSIDE ANALOGUES TREATMENT Y. Seo, Y. Yano, A. Miki, M. Saito, T. Azuma. Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan E-mail: [email protected] Background and Aims: Hepatitis B core-related antigen (HBcrAg) or hepatitis B surface antigen (HBsAg) level may reflect the transcriptional activity of cccDNA. Low level of HBcrAg or HBsAg has been reported to predict lower risk of relapse after stopping nucleoside analogues (NA) treatment. We analyzed serum level of HBcrAg and HBsAg during NA treatment, and examined factors to be declined. Methods: A total of 102 Japanese patients with chronic hepatitis B who were treated with NA for 3.7 years in median (range 1–10) were enrolled. HBV genotype determined was all C. Of all patients 79 patients was treated with Entecavir, 23 with Lamivudine combined with Adefovir dipivoxil. Serum concentration of HBsAg and HBcrAg were measured by using chemiluminescence enzyme immunoassay kits during NA treatment. Results: Serum level of HBV DNA in 90% of patients had been gone undetectable (<2.1 log copies/ml) after NA treatment. Of the 92 patients with undetectable HBV DNA, 20% had also undetectable HBcrAg (<3.0 log U/ml), and 12% had HBsAg level of <100 IU/ml which might predict lower risk of relapse after
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POSTERS stopping NA treatment. Nobody had HBsAg loss. Of the patients with undetectable HBcrAg, 39% had HBsAg level of <100 IU/ml. Of the patients with HBsAg level of <100 IU/ml, 63% had undetectable HBcrAg. Only 7.6% of all patients had undetectable HBV DNA, HBcrAg, and HBsAg level of <100 IU/ml after NA treatment. Patients with undetectable HBcrAg were older, and tended to be treated longer by NA, and had significantly lower HBV DNA level at baseline. All patients with undetectable HBcrAg were HBeAg negative and anti-HBe positive at baseline. Patients with HBsAg level of <100 IU/ml had no significant difference of background at baseline, however, HBcrAg level during NA treatment was significantly lower (3.1±0.3 vs. 4.3±1.0 log U/ml). Conclusions: Despite HBV DNA suppression, decline of HBcrAg and/or HBsAg after NA treatment was rare in Japanese patients with chronic genotype C HBV infection. HBcrAg and HBsAg provide a viral marker which is independent of HBV DNA, but not same way for monitoring NA treatment. 485 PREVALENCE AND CLINCAL SIGNIFICANCE OF OCCULT HEPATITIS B INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION M. Simonova1 , S. Pavlova2 , T. Hadzhiolova2 , A. Mihova3 , D. Takov1 , K. Katzarov1 . 1 Clinic of Gastroenterology and Hepatology, 2 Laboratory for Molecular Diagnostic of Liver Diseases, Clinic of Gastroenterology and Hepatology, 3 Department of Pathomorphology, Military Medical Academy, Sofia, Bulgaria E-mail: [email protected] Background and Aims: Occult HBV infection is reported to be more frequent in HCV-positive subjects than in healthy subjects, but there are quite contradictive data about its clinical significance. The aim of this study is to determine frequency and clinical significance of occult HBV infection in subjects with chronic HCV infection. Methods: From March 2004 to December 2010 the study prospectively included 188 subjects with chronic HCV infection (112 chronic hepatitis C, 50 liver cirrhosis, 26 HCC), all HbsAgnegative (mean age 58.5±12.02 years) and 106 healthy adults, all anti HCV Ab- and HbsAg-negative (mean age 39±24.04 years). Sera of all subjects were tested for the presence of HBV DNA by realtime PCR Cobas TaqMan® Test with detection limit of 6 IU/ml (35 copies/ml) (Roche Molecular Systems, Inc.). Two consecutive liver biopsies were preformed in 52 subjects with chronic hepatitis C and the rate of fibrosis progression was calculated. 83 HCV-positive subjects received antiviral treatment. Results: Occult HBV infection, defined in this study as positive serum HBV DNA, was found in 21.3% of subjects with chronic HCV infection and in 3.8% of healthy adults (P < 0.0001). Positive HBV DNA significantly associates with positive antiHBc Ab (P < 0.0001). Positive HBV DNA was found in 15, 2% of subjects with chronic hepatitis C, in 28% of subjects with cirrhosis and in 34.6% of subjects with HCC (P = 0.005). In subjects with chronic hepatitis C positive HBV DNA associates with more severe necro-inflammation (P = 0.001), no association was found with liver fibrosis (P = 0.545). Positive HBV DNA was found in 29.4% of subjects with progression of fibrosis and in 5.7% of the patients without fibrosis progression (P = 0.0004). Occult HBV infection didn’t affect efficacy of antiviral treatment (P = 1.000). In subjects with HCC positive HBV DNA was associated with HCC development at earlier age (41±9.89 years), compared with subjects with negative HBV DNA (66±2.12 years) (P = 0.0018). Conclusion: Occult HBV infection is more frequently found in subjects with chronic HCV infection than in healthy adults and associates with more advances liver disease and development of HCC at earlier age.
486 QUANTIFICATION OF HEPATITIS B SURFACE ANTIGEN AS A PREDICTOR OF OFF-TREATMENT SUSTAINED VIROLOGICAL RESPONSE IN CHRONIC HEPATITIS B PATIENTS TREATED WITH ORAL NUCLEOS(T)IDE ANALOGUE S.J. Suh1 , J.E. Yeon1 , E.L. Yoon1 , H.J. Lee1 , S.J. Lee1 , S.H. Kang1 , K. Kang1 , J.H. Kim1 , H.J. Yim2 , K.S. Byun1 . 1 Internal Medicine, Korea University College of Medicine, Guro Hospital, 2 Internal Medicine, Korea University College of Medicine, Ansan Hospital, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: The absolute value or reduction of hepatitis B surface antigen (HBsAg) level can be a useful marker for on-treatment response or durability of off-treatment response. We examined the appropriate cutoff value of serum HBsAg level that predict off-treatment sustained virological response in patients with chronic hepatitis B (CHB) treated with oral nucleos(t)ide analogues (NAs). Methods: From June 1998 to Dec 2010, 81 patients with CHB who discontinued NAs were enrolled [HBeAg (+), n = 50(62%)]. Oral NAs were lamivudine (n = 53), adefovir (n = 15), lamivudine combined with adefovir (n = 4), entecavir (n = 9). The mean duration of antiviral treatment and the follow-up period after discontinuation of treatment were 31±16 and 32±24 months respectively. The sustained virological response after treatment discontinuation (SVR) was defined as follows; complete (cSVR, HBV DNA undetectable) or partial (pSVR, normal ALT and detectable HBV DNA <20,000 IU/ml in HBeAg positive and HBV DNA <2,000 IU/ml in HBeAg negative). Serum HBsAg levels were determined by the ARCHITECT i2000 HBsAg (Abbott, USA, 0.09–250 IU/mL). Results: Thirty-three of 81 (40%) patients had complete or partial SVR [cSVR, 11/81 (14%); pSVR 22/81 (27%)]. The relapse rate were 37/81 (46%), 5/81 (6%) at 6 months, 12 months after discontinuation of treatment. Baseline HBV DNA, ALT, presence of HBeAg were not different in patients with or without cSVR. The mean treatment duration, the reduction of HBsAg level at 6 month on-treatment, and HBsAg level at the end of treatment were significantly different in patients with or without cSVR (47 vs. 28 months, P = 0.011; −0.9 vs. +0.2 log IU/ml, P < 0.05; 0.2 vs. 3.5 log IU/ml, P < 0.05). In multivariate analysis, only HBsAg level at the end of treatment was significant (P = 0.007). Serum HBsAg level <2 log IU/ml at the end of treatment were predictive of SVR [(AUROC, 0.991; 95% confidence interval [CI], 0.000–1.000; P < 0.05); sensitivity, 100%; specificity, 93%; positive predictive value, 69%; negative predictive value, 100%]. Conclusions: In CHB patients with long term nucleos(t)ide analogue therapy, absolute value of HBsAg off-treatment can be a predictive of SVR, and treatment discontinuation can be considered. 487 KEY PATTERNS OF HBX AND PRE-S1/S2 MUTATIONS ARE INVOLVED IN MECHANISMS UNDERLYING HBV-INDUCED HEPATOCELLULAR CARCINOMA IN VIVO V. Svicher1 , C. Mirabelli1 , V. Cento1 , R. Salpini1 , V.-C. Di Maio1 , A. Bertoli1 , C. Alteri1 , M. Pollicita1 , C. Gori2 , V. Micheli3 , A. Salso1 , G. Gubertini3 , P. Trimoulet4 , H. Fleury4 , J. Vecchiet5 , N. Iapadre6 , A. Barlattani7 , T. Mari8 , C. Pasquazzi9 , C. Sarrechia1 , F. Ceccherini-Silberstein1 , M. Andreoni1 , M. Angelico1 , C.-F. Perno1 . 1 University of Rome Tor Vergata, 2 National Institute for Infectious Diseases ’L. Spallanzani, Rome, 3 L. Sacco Hospital, Milan, Italy; 4 Hˆ opital Pellegrin Tripode, Bordeaux, France; 5 SS. Annunziata Hospital, Chieti, 6 S. Salvatore Hospital, L’Aquila, 7 S. Giacomo Hospital, 8 Regina Margherita Hospital, 9 S. Andrea Hospital, Rome, Italy E-mail: [email protected] Background: HBx and Pre-S1/S2 play a critical role in mediating HBV-induced tumorigenesis. However, little information is available
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hepatic decompensation than hepatitis B monoinfected patients. Treatment relies on pegylated interferon but this therapy leads to viral clearance in only 28% of cases. Knowledge of the viral load may provide important information for patients’ follow up. Notably, it should be useful to monitor response to current and future antiviral therapies. However no commercial reference assay including automated nucleic acid extraction and internal control (IC) is currently available for HDV-RNA quantification and in-house assays are not yet standardized. Furthermore, HDV has a high genetic diversity, eight genotypes being described; this represents a challenge for full spectrum quantitative reverse transcription (qRT)PCR. Indeed, the majority of the available assays accurately quantify only genotype 1 isolates. Methods: In this study, the development of the first duplex (including IC) one-step real-time RT-PCR assay for detection and quantification of HDV is presented. Primers and probes binding to conserved regions of the HDV antigen were designed. Tenfold dilutions series of in-vitro-transcribed HDV1 RNA were used as the standard for quantification. A commercial heterologous encapsulated-RNA was used as IC for both RNA extraction and RT-PCR. Results: The duplex qRT-PCR for HDV had an efficiency of 0.97, a regression squared value of 0.999, and a sensitivity of approximately 30 copies per reaction mixture when in vitro-transcribed RNA was used as the template. The linearity of this assay ranged from 500 to 1.7×1011 copies/mL. The repeatability (approx. 15%), and the reproducibility (range 7.4%-21.9%) were comparable to commercial HCV and HIV assays. The presence of the IC did not affect amplification of HDV RNA compared to single assay. Synthetic templates and clinical samples from different geographical origins belonging to different genotypes were successfully detected and quantified. Conclusions: We described here the first automated one-step RTPCR assay with IC for universal quantification of HDV RNA. The wide dynamic range is necessary to quantify viral RNA from clinical samples that can reach more than 1010 copies/mL. This high sensitivity and specificity assay can be easily used for routine diagnostics. 484 HEPATITIS B CORE-RELATED ANTIGEN AND QUANTITATIVE HEPATITIS B SURFACE ANTIGEN LEVELS IN JAPANESE PATIENTS WITH CHRONIC HEPATITIS B AFTER EXTENDED NUCLEOSIDE ANALOGUES TREATMENT Y. Seo, Y. Yano, A. Miki, M. Saito, T. Azuma. Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan E-mail: [email protected] Background and Aims: Hepatitis B core-related antigen (HBcrAg) or hepatitis B surface antigen (HBsAg) level may reflect the transcriptional activity of cccDNA. Low level of HBcrAg or HBsAg has been reported to predict lower risk of relapse after stopping nucleoside analogues (NA) treatment. We analyzed serum level of HBcrAg and HBsAg during NA treatment, and examined factors to be declined. Methods: A total of 102 Japanese patients with chronic hepatitis B who were treated with NA for 3.7 years in median (range 1–10) were enrolled. HBV genotype determined was all C. Of all patients 79 patients was treated with Entecavir, 23 with Lamivudine combined with Adefovir dipivoxil. Serum concentration of HBsAg and HBcrAg were measured by using chemiluminescence enzyme immunoassay kits during NA treatment. Results: Serum level of HBV DNA in 90% of patients had been gone undetectable (<2.1 log copies/ml) after NA treatment. Of the 92 patients with undetectable HBV DNA, 20% had also undetectable HBcrAg (<3.0 log U/ml), and 12% had HBsAg level of <100 IU/ml which might predict lower risk of relapse after
Journal of Hepatology 2012 vol. 56 | S71–S224
POSTERS stopping NA treatment. Nobody had HBsAg loss. Of the patients with undetectable HBcrAg, 39% had HBsAg level of <100 IU/ml. Of the patients with HBsAg level of <100 IU/ml, 63% had undetectable HBcrAg. Only 7.6% of all patients had undetectable HBV DNA, HBcrAg, and HBsAg level of <100 IU/ml after NA treatment. Patients with undetectable HBcrAg were older, and tended to be treated longer by NA, and had significantly lower HBV DNA level at baseline. All patients with undetectable HBcrAg were HBeAg negative and anti-HBe positive at baseline. Patients with HBsAg level of <100 IU/ml had no significant difference of background at baseline, however, HBcrAg level during NA treatment was significantly lower (3.1±0.3 vs. 4.3±1.0 log U/ml). Conclusions: Despite HBV DNA suppression, decline of HBcrAg and/or HBsAg after NA treatment was rare in Japanese patients with chronic genotype C HBV infection. HBcrAg and HBsAg provide a viral marker which is independent of HBV DNA, but not same way for monitoring NA treatment. 485 PREVALENCE AND CLINCAL SIGNIFICANCE OF OCCULT HEPATITIS B INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION M. Simonova1 , S. Pavlova2 , T. Hadzhiolova2 , A. Mihova3 , D. Takov1 , K. Katzarov1 . 1 Clinic of Gastroenterology and Hepatology, 2 Laboratory for Molecular Diagnostic of Liver Diseases, Clinic of Gastroenterology and Hepatology, 3 Department of Pathomorphology, Military Medical Academy, Sofia, Bulgaria E-mail: [email protected] Background and Aims: Occult HBV infection is reported to be more frequent in HCV-positive subjects than in healthy subjects, but there are quite contradictive data about its clinical significance. The aim of this study is to determine frequency and clinical significance of occult HBV infection in subjects with chronic HCV infection. Methods: From March 2004 to December 2010 the study prospectively included 188 subjects with chronic HCV infection (112 chronic hepatitis C, 50 liver cirrhosis, 26 HCC), all HbsAgnegative (mean age 58.5±12.02 years) and 106 healthy adults, all anti HCV Ab- and HbsAg-negative (mean age 39±24.04 years). Sera of all subjects were tested for the presence of HBV DNA by realtime PCR Cobas TaqMan® Test with detection limit of 6 IU/ml (35 copies/ml) (Roche Molecular Systems, Inc.). Two consecutive liver biopsies were preformed in 52 subjects with chronic hepatitis C and the rate of fibrosis progression was calculated. 83 HCV-positive subjects received antiviral treatment. Results: Occult HBV infection, defined in this study as positive serum HBV DNA, was found in 21.3% of subjects with chronic HCV infection and in 3.8% of healthy adults (P < 0.0001). Positive HBV DNA significantly associates with positive antiHBc Ab (P < 0.0001). Positive HBV DNA was found in 15, 2% of subjects with chronic hepatitis C, in 28% of subjects with cirrhosis and in 34.6% of subjects with HCC (P = 0.005). In subjects with chronic hepatitis C positive HBV DNA associates with more severe necro-inflammation (P = 0.001), no association was found with liver fibrosis (P = 0.545). Positive HBV DNA was found in 29.4% of subjects with progression of fibrosis and in 5.7% of the patients without fibrosis progression (P = 0.0004). Occult HBV infection didn’t affect efficacy of antiviral treatment (P = 1.000). In subjects with HCC positive HBV DNA was associated with HCC development at earlier age (41±9.89 years), compared with subjects with negative HBV DNA (66±2.12 years) (P = 0.0018). Conclusion: Occult HBV infection is more frequently found in subjects with chronic HCV infection than in healthy adults and associates with more advances liver disease and development of HCC at earlier age.
486 QUANTIFICATION OF HEPATITIS B SURFACE ANTIGEN AS A PREDICTOR OF OFF-TREATMENT SUSTAINED VIROLOGICAL RESPONSE IN CHRONIC HEPATITIS B PATIENTS TREATED WITH ORAL NUCLEOS(T)IDE ANALOGUE S.J. Suh1 , J.E. Yeon1 , E.L. Yoon1 , H.J. Lee1 , S.J. Lee1 , S.H. Kang1 , K. Kang1 , J.H. Kim1 , H.J. Yim2 , K.S. Byun1 . 1 Internal Medicine, Korea University College of Medicine, Guro Hospital, 2 Internal Medicine, Korea University College of Medicine, Ansan Hospital, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: The absolute value or reduction of hepatitis B surface antigen (HBsAg) level can be a useful marker for on-treatment response or durability of off-treatment response. We examined the appropriate cutoff value of serum HBsAg level that predict off-treatment sustained virological response in patients with chronic hepatitis B (CHB) treated with oral nucleos(t)ide analogues (NAs). Methods: From June 1998 to Dec 2010, 81 patients with CHB who discontinued NAs were enrolled [HBeAg (+), n = 50(62%)]. Oral NAs were lamivudine (n = 53), adefovir (n = 15), lamivudine combined with adefovir (n = 4), entecavir (n = 9). The mean duration of antiviral treatment and the follow-up period after discontinuation of treatment were 31±16 and 32±24 months respectively. The sustained virological response after treatment discontinuation (SVR) was defined as follows; complete (cSVR, HBV DNA undetectable) or partial (pSVR, normal ALT and detectable HBV DNA <20,000 IU/ml in HBeAg positive and HBV DNA <2,000 IU/ml in HBeAg negative). Serum HBsAg levels were determined by the ARCHITECT i2000 HBsAg (Abbott, USA, 0.09–250 IU/mL). Results: Thirty-three of 81 (40%) patients had complete or partial SVR [cSVR, 11/81 (14%); pSVR 22/81 (27%)]. The relapse rate were 37/81 (46%), 5/81 (6%) at 6 months, 12 months after discontinuation of treatment. Baseline HBV DNA, ALT, presence of HBeAg were not different in patients with or without cSVR. The mean treatment duration, the reduction of HBsAg level at 6 month on-treatment, and HBsAg level at the end of treatment were significantly different in patients with or without cSVR (47 vs. 28 months, P = 0.011; −0.9 vs. +0.2 log IU/ml, P < 0.05; 0.2 vs. 3.5 log IU/ml, P < 0.05). In multivariate analysis, only HBsAg level at the end of treatment was significant (P = 0.007). Serum HBsAg level <2 log IU/ml at the end of treatment were predictive of SVR [(AUROC, 0.991; 95% confidence interval [CI], 0.000–1.000; P < 0.05); sensitivity, 100%; specificity, 93%; positive predictive value, 69%; negative predictive value, 100%]. Conclusions: In CHB patients with long term nucleos(t)ide analogue therapy, absolute value of HBsAg off-treatment can be a predictive of SVR, and treatment discontinuation can be considered. 487 KEY PATTERNS OF HBX AND PRE-S1/S2 MUTATIONS ARE INVOLVED IN MECHANISMS UNDERLYING HBV-INDUCED HEPATOCELLULAR CARCINOMA IN VIVO V. Svicher1 , C. Mirabelli1 , V. Cento1 , R. Salpini1 , V.-C. Di Maio1 , A. Bertoli1 , C. Alteri1 , M. Pollicita1 , C. Gori2 , V. Micheli3 , A. Salso1 , G. Gubertini3 , P. Trimoulet4 , H. Fleury4 , J. Vecchiet5 , N. Iapadre6 , A. Barlattani7 , T. Mari8 , C. Pasquazzi9 , C. Sarrechia1 , F. Ceccherini-Silberstein1 , M. Andreoni1 , M. Angelico1 , C.-F. Perno1 . 1 University of Rome Tor Vergata, 2 National Institute for Infectious Diseases ’L. Spallanzani, Rome, 3 L. Sacco Hospital, Milan, Italy; 4 Hˆ opital Pellegrin Tripode, Bordeaux, France; 5 SS. Annunziata Hospital, Chieti, 6 S. Salvatore Hospital, L’Aquila, 7 S. Giacomo Hospital, 8 Regina Margherita Hospital, 9 S. Andrea Hospital, Rome, Italy E-mail: [email protected] Background: HBx and Pre-S1/S2 play a critical role in mediating HBV-induced tumorigenesis. However, little information is available
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