- Email: [email protected]
Clinical outcomes were comparable between chronic hepatitis B patients with virological response using oral antiviral therapy and inactive carriers when adjusting for fibrotic burden
POSTER PRESENTATIONS was confirmed. Among specific risk groups highest prevalence was noted in alcoholic liver disease and in transplant recipients. HEV seroprevalence is alarming and requires further investigation especially in patients with alcoholic cirrhosis as a potential factor influencing a disease progression. FRI-133 In HBeAg-negative chronic HBV infection, HBsAg levels profoundly vary among different HBV-genotypes and can be influenced by the degree of HBsAg variability: can quantitative HBsAg truly reflect intra-hepatic HBV reservoir? R. Salpini1, A. Battisti1, O. Anastasiou2, U. Gill3, L. Colagrossi1, A. Bertoli1, L. Fabeni4, V. Fini1, L. Piermatteo1, A. Iuvara5, V. Malagnino6, C. Cerva6, M. Lichtner7, C. Mastroianni7, G. De Sanctis8, M. Paoloni9, M. Marignani10, C. Pasquazzi10, N. Iapadre11, T. Mari12, G. Parruti13, J. Vecchiet14, L. Sarmati6, M. Andreoni6, M. Angelico15, S. Grelli1,5, P. Kennedy3, J. Verheyen2, C.F. Perno1, V. Svicher1. 1Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy; 2 Institute of Virology, University-Hospital, University Duisburg-Essen, Essen, Germany; 3Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, QMUL, London, United Kingdom; 4Antiretroviral Drug Monitoring Laboratory, National Institute for Infectious Diseases, L. Spallanzani, IRCCS; 5 Microbiology and Virology Unit; 6Infectious Diseases Unit, Tor Vergata University Hospital; 7Department of Public Health and Infectious Disease, “Sapienza” University; 8“Umberto I” University Hospital, Rome; 9 Infectious Disease Unit, “S.S. Filippo e Nicola” Hospital, Avezzano; 10 Department of Gastroenterology, “S.Andrea Hospital”, Rome; 11“San Salvatore Hospital”, L’Aquila; 12“Nuovo Regina Margherita” Hospital, Roma; 13Infectious Disease Unit, Pescara General Hospital, Pescara; 14 Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University “G. d’Annunzio” Chieti-Pescara, Chieti; 15Hepatology Unit, Tor Vergata University Hospital, Rome, Italy E-mail: [email protected] Background and Aims: HBsAg levels are proposed as a marker of the intrahepatic HBV reservoir. A recent in vitro study showed variation in HBsAg production in different HBV genotypes. Limited information is so far available on HBsAg levels in patients infected with different HBV genotypes in HBeAg-negative chronic HBV infection. Methods: This study includes 301 consecutive patients with HBeAgnegative chronic HBV infection, drug-naïve, and monitored for ≥1 year: 126 inactive carriers with persistent serum HBV-DNA ≤2,000 IU/ml and normal transaminases (defined as group A), and 175 with persistent serum HBV-DNA >2,000 IU/ml (defined as group B). HBV genotype (gen) is assessed by phylogeny. Degree of HBsAg variability is measured by calculating mean genetic distance. Results: Median (IQR) serum HBV-DNA is 2.8 (2.3–2.9) and 4.1 (3.7– 5.2) IU/ml, while median (IQR) ALT is 28 (21–38) and 34 (25–55) U/L in group A and B, respectively. HBV-genotypes are: D = 72.2%, A = 15.9%, E = 11.9% in group A, and D = 78.3%, A = 14.3%, E = 7.4% in group B. In group A, median (IQR) HBsAg is significantly lower in gen-D than in gen-A and E (730 [204–2,932] vs. 5,741 [3,526–14,290] and 10,288 [7,172–13408] IU/ml, P < 0.001). A similar result is observed in group B (3,436 [1,466–8,126] vs. 7,992 [5,069–21,221] and 10,825 [6,544– 18,216] IU/ml, P ≤ 0.01). Moreover, in group A, HBsAg levels ≤1,000 IU/ml ( proposed to define HBV gen-D patients as inactive carriers) are observed in 57.1% of gen-D, 15.0% of gen-A and 0% of gen-E (P ≤ 0.001). In group A, the degree of HBsAg C-terminus genetic variability (aa:170–226, known to modulate HBsAg secretion) is higher in gen-D and progressively declines in gen-A and E (0.033 ± 0.023 for D, 0.029 ± 0.015 for A, 0.026 ± 0.012 for E). Moreover, by stratifying group A according to HBsAg levels in gen-D, the degree of HBsAg Cterminus genetic variability is significantly higher in patients with HBsAg ≤ 1,000 IU/ml than in patients with HBsAg > 1,000 IU/ml (0.041 ± 0.024 vs. 0.022 ± 0.017, P < 0.001). S470
Conclusions: HBsAg levels in HBV-gen D are significantly lower than in gen-A and E in different phases of HBeAg-negative chronic HBV infection including the inactive carrier status. In gen-D infected patients, higher genetic variability in HBsAg C-terminus correlates with lower HBsAg levels ( presumably by impairing proper HBsAg secretion). In this setting, HBsAg levels cannot be a direct measure of intrahepatic cccDNA reservoir, supporting the role of HBV genotyping in better characterizing patients with HBeAg-negative chronic HBV infection. FRI-134 Mother-to-child transmission of hepatitis B virus in Ethiopia A. Johannessen1, K. Stene-Johansen2, B. Mekasha3, N. Berhe4. 1 Centre for Imported and Tropical Diseases, Oslo University Hospital; 2 Department of Molecular Biology, Norwegian Institute of Public Health, Oslo, Norway; 3St. Paul Hospital Millennium Medical College; 4 Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia E-mail: [email protected] Background and Aims: High viral load and positive HBeAg are established risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV). It is believed that transmission of HBV is mainly horizontal on the African continent, since most women of fertile age are HBeAg negative. Consequently, birth dose of HBV vaccine, as recommended by the World Health Organization, has not been implemented in many African countries. This study was carried out among HBV-infected pregnant and lactating women in Ethiopia in order to study: (a) risk factors for MTCT (HBeAg-status and high viral load), (b) the association between HBeAg and viral load, (c) the presence of liver fibrosis, and (d) vertical HBV transmission. Methods: Out of 1303 patients with chronic hepatitis B enrolled in a cohort study at St Paul’s Hospital Millennium Medical College in Addis Ababa, 119 were pregnant (n = 64) and/or lactating (n = 56) at inclusion, and 11 became pregnant during the first year of follow-up. Liver function tests, HBV DNAviral load (rt2000 real-time PCR, Abbott Molecular, Des Moines, IL, USA), HBeAg (VIDAS HBe/anti-HBe, BioMerieux, France) and transient elastography (Fibroscan 402, Echosense, France) were measured at baseline. Results: One-hundred-and-thirty women with 131 pregnancies were included. Median age was 28 years (range 18–41). Six of 101 women (6%) with a HBeAg result were HBeAg positive; however, 3 of these had a low viral load (<2000 IU/ml). Six of 128 women (5%) with a viral load result had a viral load above 1 million IU/ml; however, 4 of these were HBeAg negative. Median Fibroscan result (performed before or after pregnancy) was 4.4 kPa (range 1.4–20.5), and only 4 women (3%) had significant fibrosis (>7.9 kPa). Testing of the infants for HBsAg and HBV viral load is in progress. Conclusions: Significant liver fibrosis was rare. About one tenth of pregnant and lactating women had high viral load or were HBeAg positive, rendering their offspring at high risk of HBV infection. The correlation between viral load and HBeAg status was weak; thus, the use of HBeAg positivity as an indicator for MTCT risk might not be valid in an African setting. FRI-135 Clinical outcomes were comparable between chronic hepatitis B patients with virological response using oral antiviral therapy and inactive carriers when adjusting for fibrotic burden B.K. Kim1, H.S. Kim1, S.U. Kim1, J.Y. Park1, D.Y. Kim1, S.H. Ahn1, K.J. Song2, K.-H. Han1. 1Internal Medicine; 2Biostatistics, Yonsei University College of Medicine, Seoul, South Korea E-mail: [email protected] Background and Aims: We aimed to compare the risk of developing hepatocellular carcinoma (HCC) between patients with chronic hepatitis B (CHB) who achieved virological response (VR) by nucleos(t)ide analogues (NUC) (NUC-VR group) and patients with
Journal of Hepatology 2017 vol. 66 | S333–S542
POSTER PRESENTATIONS inactive CHB phase (ICHBP group), after adjusting for fibrotic burden by liver stiffness (LS) using transient elastography (TE). Methods: To adjust for imbalance between NUC-VR group (n = 1291) and ICHBP group (n = 741), propensity-score matching (PSM) was performed at 1:1 ratio, based upon following variables; age, gender, diabetes, platelet count, albumin, total bilirubin, ultrasonographic cirrhosis and LS at VR. VR was defined as serum HBV-DNA <2,000 IU/ mL with biochemical response (normal serum ALT level). After PSM was performed, cumulative rates of HCC development were assessed using Kaplan-Meier analysis with a comparison by the method of Klein and Moeschberger. Results: Among entire population, ICHBP group had a lower risk of HCC development ( p < 0.001 by log-rank test). However, when we stratified entire population according to the presence of cirrhosis, owing to the significantly higher incidence of HCC in cirrhotic patients, cumulative rates of HCC development in cirrhotic patients (n = 6 28) were similar between NUC-VR group and ICHBP group and similar results were obtained for non-cirrhotic patients (n = 1404) (both p > 0.05 by log-rank test). PSM was performed, resulting in 610 pairs and cumulative rates of HCC development were similar between NUC-VR group and ICHBP group ( p > 0.05). Conclusions: Clinical outcomes were comparable between CHB patients with VR using NUCs therapy and inactive CHB carriers when adjusting for fibrotic burden. Our results strongly support the clinical importance of appropriate HBV suppression using antiviral therapy. FRI-136 Long-term follow up of pan-genotypic hepatitis B e antigen positive patients: factors for seroconversion and effects of treatment B. Wang1, I. Carey1, M. Spaan1, M. Horner1, M. Bruce1, E. Gonsalkorala1, G. Dusheiko1,2, K. Agarwal1. 1Institute of Liver Studies, King’s College Hospital; 2UCL Medical School, London, United Kingdom E-mail: [email protected] Background and Aims: Hepatitis B e antigen (HBeAg) seroconversion reflects immune control of hepatitis B virus (HBV) infection and is an important milestone. We performed a large retrospective analysis of all HBeAg positive (+ve) patients seen at our centre over ten years with the aim of identifying factors impacting on seroconversion. Methods: HBV monoinfected patients >18 years old and HBeAg+ve at first visit between Jan 2005 and Sept 2016 were included for analysis. Demographic, clinical and laboratory data including HBV serology were collected at baseline and last follow-up. HBV DNA levels (IU/mL) were measured using TaqMan real-time PCR, and quantitative HBsAg levels (IU/mL) and HBeAg levels (S/CO) by using Abbott ARCHITECT® assay. Results: 339 patients were initially identified with 288 included in the analysis; those lost to follow up within 6 months of first visit were excluded. The patients were predominantly non-Caucasian (25.3% Black African, 53.1% East Asian) with genotypes A–F (18.4% E). Median follow up duration was 55 months (range 6–134 months). Of those with histology (n = 157), 12.1% were F5/6. 206 patients were treated; 46 with peg-IFN and 160 with nucleos(t)ide analogues. 68 (33.0%) of the treated patients achieved HBeAg seroconversion. In comparison 23 patients (28.0%) spontaneously seroconverted without treatment. Interestingly, treatment did not significantly affect seroconversion. Factors that did have an effect include age (median 31 vs. 34, p = 0.025), HBV DNA (median 8.04 vs. 6.51 log10 IU/mL, p < 0.001) and HBsAg (median 4.37 vs. 4.01 log10 IU/mL, p = 0.004) at baseline. Genotype was an important significant factor ( p < 0.001) with A being the most associated with seroconversion (67.9%), followed by E (28.3%). At last follow up, significant differences in ALT and HBsAg (0.57 log10 decline, p < 0.001) were seen in the treated patients only. Overall 6 patients achieved HBsAg loss, 1 spontaneously. 8 patients developed HCC, 3 of which did so after HBeAg seroconversion.
Conclusions: In this ethnically diverse pan-genotypic population, treatment did not appear to affect HBeAg seroconversion. Genotype E, in addition to A, appeared to be favourable. Older patients with lower baseline HBV DNA and HBsAg were more likely to seroconvert. Although treatment did not appear to affect seroconversion, it did result in normalisation of ALT and HBsAg decline. All patients achieving seroconversion remain at risk of HCC and require ongoing screening. FRI-137 Association between mutations on the basal core promoter region and hepatocellular carcinoma in Vietnamese chronic hepatitis B patients P.T. Le Hoa1, C.H.T. Nguyen1. 1Uni of Pharmacy and Medicine of Ho Chi Minh, Ho Chi Minh, Vietnam E-mail: [email protected] Background and Aims: Mutations on S, basal core promoter (BCP) and X genes have been recognized related with chronic liver inflammation and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Mutations at nucleotide 1753, 1762 and 1764 on the BCP region change the overlapped sequence on the X gene and increase the risk of HCC. These mutations posed more affects in genotype C distribution areas. We aimed to characterize A1762T, G1764A and T1753V mutations and their association with HCC in Vietnamese CHB patients. Methods: The cross sectional study was conducted from June 2013 to January 2016 at the Hospital for Tropical Diseases and the Medical Center, University of Medicine and Pharmacy (UMP) of HCM city. Patients with HBsAg positive more than 6 months, HBV DNA over 3 log copies/ml and HBV genotype identified were selected stratifily based on cirrhotic and HCC status. Mutations were identified by automated sequencing at the UMP Center for Molecular BioMedicine. Results: The population composed of 451 patients (138 chronic carrier, 210 active hepatitis, 58 cirrhosis and 45 HCC). There were 68% male, 52% HBeAg positive, 30% genotype C and 52% of age over 40, 17.1% with cirrhosis and 10% with HCC. The rate of A1762T/G1764A and A1762T/G1764A/T1753V mutations were 40.4% and 17.7%. Most of the T1753V mutation cases (80/94) went with A1762T/G1764A mutation. The rate of A1762T/G1764A and A1762T/G1764A/T1753V were higher in the HCC group (68.9% and 44.4% vs. 37.2% and 14.8%, p < 0.001). Mutivariate analysis found higher odds ratios for men ( p = 0.007), age over 40 ( p < 0.001), cirrhotic status ( p = 0.02), genotype C ( p = 0.02), BCP mutation ( p = 0.001) and found lower odd ratio for HBV DNA > 8 log copies/ml ( p = 0.01). In the analysis which stratified the BCP mutation variable to 3 separate groups (A1762T/G1764A, A1762T/G1764A/T1753V and single T1753V), only the triple mutation of A1762/G1764A/T1753V group revealed higher risk of HCC (OR = 4.72; 95% CI, 1.83–12.17; p = 0.001). Conclusions: T1753V, A1762T and G1764A mutations were frequently detected in BCP region. T1753V mutation was occurred on the basis of A1762T/G1764A mutation. The co-existence of these three single mutations T1753V, A1762T and G1764A was associated with HCC. FRI-138 2′-C-methylcytidine inhibits hepatitis E virus replication but antagonizing ribavirin C. Qu1, W. Wang1, L. Xu1, Y. Yin1, Q. Pan1, M. Peppelenbosch1. 1 Gastroenterology and Hepatology, ERASMUSMC, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Hepatitis E virus (HEV) infection has emerged as a global issue, whereas no approved medication is available. Although ribavirin is effective as off-label treatment for chronic hepatitis E, a substantial proportion of patients develop resistance and eventually fail to clear the virus. The viral polymerase inhibitor 2′-C-methylcytidine (2CMC) has been shown capable of inhibiting a variety of RNA viruses, including hepatitis C virus (HCV).
Journal of Hepatology 2017 vol. 66 | S333–S542
S471
Conclusions: HBsAg levels in HBV-gen D are significantly lower than in gen-A and E in different phases of HBeAg-negative chronic HBV infection including the inactive carrier status. In gen-D infected patients, higher genetic variability in HBsAg C-terminus correlates with lower HBsAg levels ( presumably by impairing proper HBsAg secretion). In this setting, HBsAg levels cannot be a direct measure of intrahepatic cccDNA reservoir, supporting the role of HBV genotyping in better characterizing patients with HBeAg-negative chronic HBV infection. FRI-134 Mother-to-child transmission of hepatitis B virus in Ethiopia A. Johannessen1, K. Stene-Johansen2, B. Mekasha3, N. Berhe4. 1 Centre for Imported and Tropical Diseases, Oslo University Hospital; 2 Department of Molecular Biology, Norwegian Institute of Public Health, Oslo, Norway; 3St. Paul Hospital Millennium Medical College; 4 Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia E-mail: [email protected] Background and Aims: High viral load and positive HBeAg are established risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV). It is believed that transmission of HBV is mainly horizontal on the African continent, since most women of fertile age are HBeAg negative. Consequently, birth dose of HBV vaccine, as recommended by the World Health Organization, has not been implemented in many African countries. This study was carried out among HBV-infected pregnant and lactating women in Ethiopia in order to study: (a) risk factors for MTCT (HBeAg-status and high viral load), (b) the association between HBeAg and viral load, (c) the presence of liver fibrosis, and (d) vertical HBV transmission. Methods: Out of 1303 patients with chronic hepatitis B enrolled in a cohort study at St Paul’s Hospital Millennium Medical College in Addis Ababa, 119 were pregnant (n = 64) and/or lactating (n = 56) at inclusion, and 11 became pregnant during the first year of follow-up. Liver function tests, HBV DNAviral load (rt2000 real-time PCR, Abbott Molecular, Des Moines, IL, USA), HBeAg (VIDAS HBe/anti-HBe, BioMerieux, France) and transient elastography (Fibroscan 402, Echosense, France) were measured at baseline. Results: One-hundred-and-thirty women with 131 pregnancies were included. Median age was 28 years (range 18–41). Six of 101 women (6%) with a HBeAg result were HBeAg positive; however, 3 of these had a low viral load (<2000 IU/ml). Six of 128 women (5%) with a viral load result had a viral load above 1 million IU/ml; however, 4 of these were HBeAg negative. Median Fibroscan result (performed before or after pregnancy) was 4.4 kPa (range 1.4–20.5), and only 4 women (3%) had significant fibrosis (>7.9 kPa). Testing of the infants for HBsAg and HBV viral load is in progress. Conclusions: Significant liver fibrosis was rare. About one tenth of pregnant and lactating women had high viral load or were HBeAg positive, rendering their offspring at high risk of HBV infection. The correlation between viral load and HBeAg status was weak; thus, the use of HBeAg positivity as an indicator for MTCT risk might not be valid in an African setting. FRI-135 Clinical outcomes were comparable between chronic hepatitis B patients with virological response using oral antiviral therapy and inactive carriers when adjusting for fibrotic burden B.K. Kim1, H.S. Kim1, S.U. Kim1, J.Y. Park1, D.Y. Kim1, S.H. Ahn1, K.J. Song2, K.-H. Han1. 1Internal Medicine; 2Biostatistics, Yonsei University College of Medicine, Seoul, South Korea E-mail: [email protected] Background and Aims: We aimed to compare the risk of developing hepatocellular carcinoma (HCC) between patients with chronic hepatitis B (CHB) who achieved virological response (VR) by nucleos(t)ide analogues (NUC) (NUC-VR group) and patients with
Journal of Hepatology 2017 vol. 66 | S333–S542
POSTER PRESENTATIONS inactive CHB phase (ICHBP group), after adjusting for fibrotic burden by liver stiffness (LS) using transient elastography (TE). Methods: To adjust for imbalance between NUC-VR group (n = 1291) and ICHBP group (n = 741), propensity-score matching (PSM) was performed at 1:1 ratio, based upon following variables; age, gender, diabetes, platelet count, albumin, total bilirubin, ultrasonographic cirrhosis and LS at VR. VR was defined as serum HBV-DNA <2,000 IU/ mL with biochemical response (normal serum ALT level). After PSM was performed, cumulative rates of HCC development were assessed using Kaplan-Meier analysis with a comparison by the method of Klein and Moeschberger. Results: Among entire population, ICHBP group had a lower risk of HCC development ( p < 0.001 by log-rank test). However, when we stratified entire population according to the presence of cirrhosis, owing to the significantly higher incidence of HCC in cirrhotic patients, cumulative rates of HCC development in cirrhotic patients (n = 6 28) were similar between NUC-VR group and ICHBP group and similar results were obtained for non-cirrhotic patients (n = 1404) (both p > 0.05 by log-rank test). PSM was performed, resulting in 610 pairs and cumulative rates of HCC development were similar between NUC-VR group and ICHBP group ( p > 0.05). Conclusions: Clinical outcomes were comparable between CHB patients with VR using NUCs therapy and inactive CHB carriers when adjusting for fibrotic burden. Our results strongly support the clinical importance of appropriate HBV suppression using antiviral therapy. FRI-136 Long-term follow up of pan-genotypic hepatitis B e antigen positive patients: factors for seroconversion and effects of treatment B. Wang1, I. Carey1, M. Spaan1, M. Horner1, M. Bruce1, E. Gonsalkorala1, G. Dusheiko1,2, K. Agarwal1. 1Institute of Liver Studies, King’s College Hospital; 2UCL Medical School, London, United Kingdom E-mail: [email protected] Background and Aims: Hepatitis B e antigen (HBeAg) seroconversion reflects immune control of hepatitis B virus (HBV) infection and is an important milestone. We performed a large retrospective analysis of all HBeAg positive (+ve) patients seen at our centre over ten years with the aim of identifying factors impacting on seroconversion. Methods: HBV monoinfected patients >18 years old and HBeAg+ve at first visit between Jan 2005 and Sept 2016 were included for analysis. Demographic, clinical and laboratory data including HBV serology were collected at baseline and last follow-up. HBV DNA levels (IU/mL) were measured using TaqMan real-time PCR, and quantitative HBsAg levels (IU/mL) and HBeAg levels (S/CO) by using Abbott ARCHITECT® assay. Results: 339 patients were initially identified with 288 included in the analysis; those lost to follow up within 6 months of first visit were excluded. The patients were predominantly non-Caucasian (25.3% Black African, 53.1% East Asian) with genotypes A–F (18.4% E). Median follow up duration was 55 months (range 6–134 months). Of those with histology (n = 157), 12.1% were F5/6. 206 patients were treated; 46 with peg-IFN and 160 with nucleos(t)ide analogues. 68 (33.0%) of the treated patients achieved HBeAg seroconversion. In comparison 23 patients (28.0%) spontaneously seroconverted without treatment. Interestingly, treatment did not significantly affect seroconversion. Factors that did have an effect include age (median 31 vs. 34, p = 0.025), HBV DNA (median 8.04 vs. 6.51 log10 IU/mL, p < 0.001) and HBsAg (median 4.37 vs. 4.01 log10 IU/mL, p = 0.004) at baseline. Genotype was an important significant factor ( p < 0.001) with A being the most associated with seroconversion (67.9%), followed by E (28.3%). At last follow up, significant differences in ALT and HBsAg (0.57 log10 decline, p < 0.001) were seen in the treated patients only. Overall 6 patients achieved HBsAg loss, 1 spontaneously. 8 patients developed HCC, 3 of which did so after HBeAg seroconversion.
Conclusions: In this ethnically diverse pan-genotypic population, treatment did not appear to affect HBeAg seroconversion. Genotype E, in addition to A, appeared to be favourable. Older patients with lower baseline HBV DNA and HBsAg were more likely to seroconvert. Although treatment did not appear to affect seroconversion, it did result in normalisation of ALT and HBsAg decline. All patients achieving seroconversion remain at risk of HCC and require ongoing screening. FRI-137 Association between mutations on the basal core promoter region and hepatocellular carcinoma in Vietnamese chronic hepatitis B patients P.T. Le Hoa1, C.H.T. Nguyen1. 1Uni of Pharmacy and Medicine of Ho Chi Minh, Ho Chi Minh, Vietnam E-mail: [email protected] Background and Aims: Mutations on S, basal core promoter (BCP) and X genes have been recognized related with chronic liver inflammation and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Mutations at nucleotide 1753, 1762 and 1764 on the BCP region change the overlapped sequence on the X gene and increase the risk of HCC. These mutations posed more affects in genotype C distribution areas. We aimed to characterize A1762T, G1764A and T1753V mutations and their association with HCC in Vietnamese CHB patients. Methods: The cross sectional study was conducted from June 2013 to January 2016 at the Hospital for Tropical Diseases and the Medical Center, University of Medicine and Pharmacy (UMP) of HCM city. Patients with HBsAg positive more than 6 months, HBV DNA over 3 log copies/ml and HBV genotype identified were selected stratifily based on cirrhotic and HCC status. Mutations were identified by automated sequencing at the UMP Center for Molecular BioMedicine. Results: The population composed of 451 patients (138 chronic carrier, 210 active hepatitis, 58 cirrhosis and 45 HCC). There were 68% male, 52% HBeAg positive, 30% genotype C and 52% of age over 40, 17.1% with cirrhosis and 10% with HCC. The rate of A1762T/G1764A and A1762T/G1764A/T1753V mutations were 40.4% and 17.7%. Most of the T1753V mutation cases (80/94) went with A1762T/G1764A mutation. The rate of A1762T/G1764A and A1762T/G1764A/T1753V were higher in the HCC group (68.9% and 44.4% vs. 37.2% and 14.8%, p < 0.001). Mutivariate analysis found higher odds ratios for men ( p = 0.007), age over 40 ( p < 0.001), cirrhotic status ( p = 0.02), genotype C ( p = 0.02), BCP mutation ( p = 0.001) and found lower odd ratio for HBV DNA > 8 log copies/ml ( p = 0.01). In the analysis which stratified the BCP mutation variable to 3 separate groups (A1762T/G1764A, A1762T/G1764A/T1753V and single T1753V), only the triple mutation of A1762/G1764A/T1753V group revealed higher risk of HCC (OR = 4.72; 95% CI, 1.83–12.17; p = 0.001). Conclusions: T1753V, A1762T and G1764A mutations were frequently detected in BCP region. T1753V mutation was occurred on the basis of A1762T/G1764A mutation. The co-existence of these three single mutations T1753V, A1762T and G1764A was associated with HCC. FRI-138 2′-C-methylcytidine inhibits hepatitis E virus replication but antagonizing ribavirin C. Qu1, W. Wang1, L. Xu1, Y. Yin1, Q. Pan1, M. Peppelenbosch1. 1 Gastroenterology and Hepatology, ERASMUSMC, Rotterdam, The Netherlands E-mail: [email protected] Background and Aims: Hepatitis E virus (HEV) infection has emerged as a global issue, whereas no approved medication is available. Although ribavirin is effective as off-label treatment for chronic hepatitis E, a substantial proportion of patients develop resistance and eventually fail to clear the virus. The viral polymerase inhibitor 2′-C-methylcytidine (2CMC) has been shown capable of inhibiting a variety of RNA viruses, including hepatitis C virus (HCV).
Journal of Hepatology 2017 vol. 66 | S333–S542
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