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Hepatitis B e antigen (HBeAg) loss is a key event in the natural history of chronic hepatitis B virus infection. The rate and determinants of HBeAg loss depend upon cohort characteristics at baseline. Few studies have examined the age-dependent rate, and none have examined the effect of patient sex and ethnicity on the age-dependant rate. The study of age-dependent rates requires the identification and long-term follow-up of a pediatric cohort. We have studied the age-dependent rate of HBeAg loss, and the rate of HBeAg loss measured from baseline, in a multi-ethnic cohort of 454 pediatric patients. During observation, HBeAg loss was observed in 121/303 (39.9%) HBeAg-positive patients. The rate of HBeAg loss was greater in the second versus the first and third decades of life. The age-related rate of HBeAg loss was clearly affected by patient sex and ethnicity, with earlier loss observed for males and for White versus both South Asian and Chinese ethnicities. When measured from baseline, Chinese patients had a slower rate of HBeAg loss in comparison with White patients. In multivariate analysis of HBeAg loss during prolonged follow-up, male sex, older age, and White ethnicity were associated with HBeAg loss, but antiviral treatment was not., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Asian, Pacific Islander, African, and Caribbean communities in the U.S. are heavily impacted by chronic hepatitis B (HBV) and hepatocellular carcinoma (HCC). Educating these groups about the link between the two diseases is imperative to improve screening rates and health outcomes. This study aims to identify and incorporate preferred mediated communication methods into community-specific educational campaigns which emphasize the connection between the conditions, to promote uptake of prevention and management behaviors for HBV and HCC. Fifteen focus groups and two key informant interviews were conducted with Micronesian, Chinese, Hmong, Nigerian, Ghanaian, Vietnamese, Korean, Somali, Ethiopian, Filipino, Haitian, and Francophone West African communities. Data were analyzed using thematic coding and analysis. Findings demonstrate that all communities preferred materials be offered in both English and native languages and requested that materials highlight the connection between HBV and HCC. Delivery channel preferences and messaging themes varied by group. This study provides insight into community-specific preferences for learning about HBV and HCC. The findings can be used to design culturally and linguistically tailored, multi-platform, health education campaigns to facilitate improved HBV screening and vaccination rates and increase knowledge about HCC risk among highly impacted communities in the U.S.

Background & Aims: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium., Methods: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses., Results: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001)., Conclusions: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed., Impact and Implications: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Chronic Hepatitis B virus infection, the leading cause of hepatocellular carcinoma worldwide, disproportionately affects Asian Pacific Islanders (APIs) within the USA. Among APIs, the Hmong have one of the highest rates of chronic HBV infection-up to 18% compared to 0.1% for non-Hispanic Caucasians. This study sought to estimate the prevalence of HBV infection and assess the need for community HBV education within Milwaukee County's Hmong., Methods: Between 3/2013 and 12/2019, 287 Hmong participants were screened for HBV and 271 were provided targeted HBV education to evaluate its impact on HBV knowledge., Results: Among participants screened, 178 (62%) were immune; 77 (27%) susceptible; 27 (9%) positive; and 5 (2%) in a "gray zone." Targeted health education showed statistically significant improvement in HBV knowledge., Discussion: With 38% lacking immunity to HBV and 9% with active infection, there remains a significant need for HBV screening, vaccination, and education in Milwaukee's Hmong community., (© 2021. W. Montague Cobb-NMA Health Institute.)

Background and Aims: Chronic hepatitis B (CHB) affects >290 million persons globally, and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression (LR) and machine learning (ML; random forest) models to accurately identify patients with HBV, using only easily obtained demographic data from a population-based data set., Approach and Results: We identified participants with data on HBsAg, birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, and 10; n = 39,119) and validation (cycles 1, 4, 7, and 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR], 0.28; p < 0.001); male sex (aOR, 1.49; p = 0.0080); Black and Asian/other versus White (aOR, 5.23 and 9.13; p < 0.001 for both); and being USA-born (vs. foreign-born; aOR, 0.14; p < 0.001). We found that the ML model consistently outperformed the LR model, with higher area under the receiver operating characteristic values (0.83 vs. 0.75 in validation cohort; p < 0.001) and better differentiation of high- and low-risk persons., Conclusions: Our ML model provides a simple, targeted approach to HBV screening, using only easily obtained demographic data., (© 2021 American Association for the Study of Liver Diseases.)

Correlations between serum hepatitus B virus (HBV) pregenomic RNA (pgRNA), hepatitus B surface antigen (HBsAg), and hepatitus B core-related antigen (HBcrAg) levels, and influencing factors of serum HBV pgRNA levels in Chinese chronic hepatitis B (CHB) patients are rarely reported. This was a retrospective cohort study consisting of 204 outpatients with CHB. Serum levels of HBV pgRNA, HBsAg, and HBcrAg were quantitative measured in frozen blood samples. The linear regression and multivariate logistic regression analysis were performed to determine associated factors of serum HBV pgRNA levels. In this cohort, the median serum HBV pgRNA level was 4.12 log10 copies/ml and 33.33% (68/204) of them had serum HBV pgRNA under low limit of detection (LLD) (<500 copies/ml); and the percentage of patients with serum HBV pgRNA under LLD in hepatitis B e antigen (HBeAg)-positive patients was significantly lower than that in HBeAg-negative patients (15.75% [23/46] vs. 77.59% [45/58], p < .001). Overall, serum HBV pgRNA strongly correlated with HBcrAg (r = 0.760, p < .001), and moderately correlated with HBV DNA (r = 0.663, p < .001) and HBsAg (r = 0.670, p < .001). As compared with HBsAg and HBV DNA, only HBcrAg showed stable correlation with serum HBV pgRNA both in HBeAg-positive and HBeAg-negative patients. Serum HBV pgRNA level differed between HBeAg-positive and HBeAg-negative patients; and it had better and more stable correlation with serum HBcrAg than serum HBV DNA and HBsAg, irrespective of HBeAg status., (© 2020 Wiley Periodicals LLC.)

Background: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria., Aim: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection., Methods: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV)., Results: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively., Conclusion: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

Background: A greater understanding of the determinants of health behavior among those with and at-risk of chronic hepatitis B virus (HBV) infection is needed for effective design and implementation of public health initiatives., Aims: To determine factors associated with (1) willingness to accept HBV antiviral treatment and (2) satisfaction with provider communication regarding HBV care in a diverse cohort of HBV-infected patients., Methods: Using a multifaceted model of health behavior, the Health Behavior Framework, we conducted a comprehensive assessment of knowledge, attitudes, beliefs, and barriers to HBV care., Results: We enrolled 510 patients, with mean age 46 years; 53.1% men; and 71.6% Asian or Hawaiian/Pacific Islander. Patients were knowledgeable about HBV infection, but one-fifth did not think that HBV was a treatable disease; over a quarter felt it was so common among family and friends that it did not concern them, and less than half of patients believed they were likely to have liver problems or transmit HBV to others during their lifetime. Perceived susceptibility to disease risk was the only independent predictor of willingness to accept HBV treatment (β = 0.23, p = 0.0005), and contrary to expectations, having a doctor that speaks the same language was predictive of lower patient satisfaction with provider communication about their HBV care (β = - 0.65, p < 0.0001)., Conclusions: Patients with greater perceived susceptibility to the health consequences of HBV infection are more likely to accept treatment, and patient-provider language concordance impacts patient satisfaction with communication regarding HBV care in an unexpected direction.

Background & Aims: A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort., Methods: We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset., Results: The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) [total, with or without cirrhosis]). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038)., Conclusion: In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF., Lay Summary: In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis., Competing Interests: Conflict of interest GV Papatheodoridis: advisor/lecturer for Abbvie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, Spring Bank; research grants Abbvie, Gilead. GN Dalekos: advisor/lecturer for Abbvie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Roche; grant support from Bristol-Myers Squibb, Gilead, Roche. R Idilman: Nothing to declare. V Sypsa: advisor/lecturer for Abbvie, Gilead, Janssen; research grants from Abbvie, Gilead. F van Boemmel: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, Novartis, Roche; research grants from Bristol- Myers Squibb, Gilead, Janssen, Roche, Siemens; consultant for Abbvie, Gilead, Roche. M Buti: advisor/lecturer for Abbvie, Arbutus, Bristol-Myers Squibb, Gilead, Glaxo Smith-Kleine, Merck, Roche, Spring Bank. JL Calleja: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck. J Goulis: advisor/lecturer for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche; research grant from Bristol-Myers Squibb. S Manolakopoulos: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche; grants from Bristol-Myers Squibb, Gilead. A Loglio: lecturer for Gilead, MYR Pharmaceuticals. M Papatheodoridi: Nothing to declare. N Gatselis: advisor for Gilead. R Veelken: Nothing to declare. M Lopez-Gomez: Nothing to declare. BE Hansen: Nothing to declare. S Savvidou: Nothing to declare. A Kourikou: Nothing to declare. I Vlachogiannakos: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, Merck Sharp & Dohme, Novartis, Roche. K Galanis: Nothing to declare. C Yurdaydin: speaker's bureau and/or advisor for AbbVie, Bristol-Myers Squibb, Gilead, Merck, Roche; research grant from Bristol-Myers Squibb. R Esteban: advisor/lecturer for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis. HLA Janssen: consultant for and grants from AbbVie, Arbutus, Bristol-Myers Squibb, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., Viroclinics. T Berg: advisor/consultant/lecturer for Abbvie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex; Research support from Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche. P Lampertico: speaking bureau/advisor for Abbvie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma, Roche. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects minorities in the USA. Undiagnosed HBV precludes HCC screening and contributes to late-stage cancer presentation and decreased survival. Barriers to HBV and HCC screening include lack of insurance and limited diffusion of guidelines. We aimed to assess knowledge about HBV and HCC screening indications and explore barriers to screening., Methods: We surveyed trainees from the University of Miami/Jackson Memorial Hospitals, Palmetto General Hospital, and Mount Sinai Medical Center. We assessed knowledge using clinical vignettes. We performed bivariate and Chi-squared analyses., Results: There were 183 respondents; median age was 31 and 52% were male. The sample was 35% Hispanic, 29% White, 18% Asian, and 9% Black. Training department was Internal Medicine, 71%; Family Medicine, 11%; Infectious Diseases, 6%; or Gastroenterology, 7%. Only 59% correctly estimated national HBV prevalence; 25% correctly estimated global prevalence. In vignettes with behavioral risk factors, trainees correctly advised screening, 63-96%. However, when the risk factor was the birthplace, correct responses ranged from 33 to 53%. Overall, 45% chose an incorrect combination of HBV screening tests. Perceived barriers to screening included limited expertise in screening of immigrants and limited patient education. Respondents were more likely to recommend HCC screening in cirrhotic patients versus non-cirrhotic HBV patients. Key barriers to HCC screening included uncertainty about HCC guidelines and patient financial barriers., Conclusions: Knowledge of HBV and HCC screening recommendations is suboptimal among trainees. Efforts to broadly disseminate HBV and HCC guidelines through targeted educational interventions are needed.

The N-terminus of the hepatitis B virus (HBV) large surface protein (LHB) differs with respect to genotypes. Compared to the amino terminus of genotype (Gt)D, in GtA, GtB and GtC, an additional identical 11 amino acids (aa) are found, while GtE and GtG share another similar 10 aa. Variants of GtB and GtC affecting this N-terminal part are associated with hepatoma formation. Deletion of these amino-terminal 11 aa in GtA reduces the amount of LHBs and changes subcellular accumulation (GtA-like pattern) to a dispersed distribution (GtD-like pattern). Vice versa, the fusion of the GtA-derived N-terminal 11 aa to GtD causes a GtA-like phenotype. However, insertion of the corresponding GtE-derived 10 aa to GtD has no effect. Deletion of these 11aa decreases filament size while neither the number of released viral genomes nor virion size and infectivity are affected. A negative regulatory element (aa 2-8) and a dominant positive regulatory element (aa 9-11) affecting the amount of LHBs were identified. The fusion of this motif to eGFP revealed that the effect on protein amount and subcellular distribution is not restricted to LHBs. These data identify a novel region in the N-terminus of LHBs affecting the amount and subcellular distribution of LHBs and identify release-promoting and -inhibiting aa residues within this motive.

Chronic hepatitis B virus (HBV) infection is related to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and the interplay between the virus and host immune response leads to different outcomes of the infection. PR domain zinc finger protein 1 (PRDM1) and autophagy-related protein 5 (ATG5) are involved in immune response and HBV infection. An intergenic region between PRDM1 and ATG5 (PRDM1-ATG5 region) has been identified, and single-nucleotide polymorphisms (SNPs) in this region were shown to be involved in immune regulation. This study investigated the functionally relevant rs548234, rs6937876, and rs6568431 polymorphisms at the PRDM1-ATG5 region in a Han Chinese population (403 patients with chronic HBV infection [171 chronic hepatitis, 119 cirrhosis, and 113 HCC], 70 infection resolvers, and 196 healthy controls). The frequencies of the rs6568431 allele A in HBV patients (P = .005) and genotype CA in infection resolvers (P = .005) were significantly higher than in healthy controls. In the dominant model, HCC patients had significantly higher frequencies of rs548234 genotypes CC + TC than cirrhosis patients (P = .009). Rs548234 was an independent factor for HCC in comparison with either cirrhosis (P = .005) or all chronic HBV infection without HCC (P = .018). Functional annotation showed evidence of the role of the SNPs in gene regulation. In conclusion, through this study it is revealed for the first time that rs6568431 may be associated with susceptibility to HBV infection and that rs548234 may be associated with HCC risk in chronic HBV infection, supporting the presence of HBV-related disease-causing regulatory polymorphisms in the PRDM1-ATG5 intergenic region., (© 2019 Wiley Periodicals, Inc.)

Background & Aims: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting., Methods: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5., Results: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups., Conclusions: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy., Lay Summary: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required., Competing Interests: Conflict of interest GV Papatheodoridis: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, Spring Bank; research grants Abbvie, Bristol-Myers Squibb, Gilead. V Sypsa: advisor/lecturer for Abbvie, Gilead; research grants from Abbvie, Gilead. GN Dalekos: advisor/lecturer for Abbvie, Bayer, Genkyotex, Gilead, Ipsen, Janssen, Novartis, Pfizer, Roche; research grants from Abbvie, Gilead. C Yurdaydin: speaker's bureau and/or advisor for AbbVie, Bristol-Myers Squibb, Gilead, Merck, Roche; research grant from Bristol-Myers Squibb. F van Boemmel: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, Novartis, Roche; research grants from Bristol-Myers Squibb, Gilead, Janssen, Roche, Siemens; consultant for Abbvie, Gilead, Roche. M Buti: advisor/lecturer for Abbvie, Arbutus, Bristol-Myers Squibb, Gilead, Glaxo Smith-Kleine, Merck, Roche, Spring Bank. JL Calleja: advisor/lecturer for Abbvie , Bristol-Myers Squibb, Gilead, Janssen, Merck. H Chi: Nothing to declare. J Goulis: advisor/lecturer for Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche; research grant from Gilead. S Manolakopoulos: advisor/lecturer for Abbvie, Gilead, GlaxoSmithKline, Ipsen, Merck Sharp & Dohme, Novartis, Roche; research grants from Abbvie, Gilead. A Loglio: advisor/lecturer for Gilead, MYR Pharma. T Voulgaris: Nothing to declare. N Gatselis: Nothing to declare. O Keskın: Nothing to declare. R Veelken: Nothing to declare. M Lopez-Gomez: Nothing to declare. BE Hansen: Nothing to declare. S Savvidou: Nothing to declare. A Kourikou: Nothing to declare. I Vlachogiannakos: advisor/lecturer for Abbvie, Bristol-Myers Squibb, Gilead, Merck Sharp & Dohme, Novartis, Roche. K Galanis: Nothing to declare. R Idilman: Nothing to declare. R Esteban: advisor/lecturer for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis. HLA Janssen: consultant for and grants from AbbVie, Arbutus, Bristol-Myers Squibb, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., Viroclinics. T Berg: advisor/consultant/lecturer for Abbvie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex; Research support from Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche. P Lampertico: speaking bureau/advisor for Abbvie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma, Roche. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: People living with human immunodeficiency virus (HIV) have an increased risk of other infections, including viral hepatitis, which can complicate the treatment and progression of the disease. We sought to characterize Alabama cases of HIV co-infected with hepatitis C virus or hepatitis B virus., Methods: Using surveillance data, we defined co-infection as a person identified as having hepatitis C or hepatitis B and HIV during 2007-2016. We compared demographics, outcomes, and risk factors for co-infected versus monoinfected individuals with HIV. We mapped co-infected individuals' distribution., Results: Of 5824 people with HIV, 259 (4.4%) were co-infected with hepatitis C (antibody or RNA positive) and 145 (2.5%) with hepatitis B (surface antigen, e antigen, or DNA positive) during 2007-2016. Individuals with HIV and hepatitis C had a greater odds of injection drug use (adjusted odds ratio 9.7; 95% confidence interval 6.0-15.5). Individuals with HIV and hepatitis B had a greater odds of male-to-male sexual contact (adjusted odds ratio 1.7; 95% confidence interval 1.1-2.6). Co-infection was greater in urban public health districts., Conclusions: We identified risk behaviors among Alabama populations associated with increased odds for HIV and viral hepatitis co-infection. Outreach, prevention, testing, and treatment resources can be targeted to these populations.

Chronic hepatitis B (CHB) disproportionately affects non-US born Asians. The Hmong have been shown to have the highest rates of CHB and mortality from liver cancer compared to other Asian groups. From September 2014 to September 2017, testing for CHB within Sacramento County was conducted through community-based testing events and an electronic health record alert that identified Asian patients by surname. Demographic and laboratory data were collected for analysis and patients were followed through the study period to assess linkage to care and treatment to compare differences between Asian origin groups. Of 4350 patients tested for CHB, 318 (7.3%) were HBsAg positive, including 90 Chinese, 47 Hmong, and 101 Vietnamese. Hmong were more likely to have Medicaid insurance compared to other Asian origin groups (15%, p < 0.001). Hmong had significantly lower rates of hepatitis B DNA testing (p < 0.001), referral to hepatology (p < 0.001), attendance of first (p < 0.001) and second medical visit (p = 0.0003), and lower rates of antiviral treatment compared to other Asian origin groups. Hmong also had the highest proportion of non-English speakers (p < 0.001). Hmong patients in the Sacramento CHB testing and linkage to care program experience socioeconomic disadvantages compared to Vietnamese and Chinese patients. These factors may contribute to decreased linkage of care and decreased anti-viral treatment rates for CHB.

Background: Early detection, identification, and treatment of chronic hepatitis B through screening is vital for those at increased risk, e.g. born in hepatitis B endemic countries. In the Netherlands, Moroccan immigrants show low participation rates in health-related screening programmes. Since social networks influence health behaviour, we investigated whether similar screening intentions for chronic hepatitis B cluster within social networks of Moroccan immigrants., Methods: We used respondent-driven sampling (RDS) where each participant ("recruiter") was asked to complete a questionnaire and to recruit three Moroccans ("recruitees") from their social network. Logistic regression analyses were used to analyse whether the recruiters' intention to request a screening test was similar to the intention of their recruitees., Results: We sampled 354 recruiter-recruitee pairs: for 154 pairs both participants had a positive screening intention, for 68 pairs both had a negative screening intention, and the remaining 132 pairs had a discordant intention to request a screening test. A tie between a recruiter and recruitee was associated with having the same screening intention, after correction for sociodemographic variables (OR 1.70 [1.15-2.51])., Conclusions: The findings of our pilot study show clustering of screening intention among individuals in the same network. This provides opportunities for social network interventions to encourage participation in hepatitis B screening initiatives.

Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase and analysed for variables associated with high MTCT risk (defined by HBV DNA level >200 000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4% were considered high risk for MTCT and, of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 and 50 U/L were associated with higher likelihood for being high risk for MTCT. Only 0.8% of pregnancies low risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time., (© 2019 John Wiley & Sons Ltd.)

Background: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort., Methods: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score., Results: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001)., Conclusions: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Routine antenatal screening for chronic hepatitis B (HBV) in countries with high migrant populations provides an opportunity to monitor trends in HBV prevalence and can inform estimates locally and in countries with limited seroprevalence data. We linked perinatal birth register records with HBV notifications in the largest Australian state, over the period 2000-2016. Among women aged 15-44 years, we estimated age-standardized chronic HBV prevalence overall and by country of birth and also estimated trends in age-standardized HBV prevalence over time using regression modelling. Among 903 831 women, 8001 linked to a chronic HBV infection record (overall age-standardized prevalence 0.76%, 95% CI: 0.74-0.78). Prevalence varied by country of birth with the highest estimates among women born in Sierra Leone (11.13%, 95% CI: 8.29-13.96), Taiwan (8.08%, 95% CI: 6.74%-9.43%), Cambodia (7.47%, 95% CI: 6.50%-8.45%) and Vietnam (7.36%, 95% CI: 6.97%-7.75%); more moderate estimates among women from North Korea (2.76%, 95% CI: 1.99-3.53) and Samoa (2.64%, 95% CI: 1.99%-3.29%); prevalence was 0.18% (95% CI: 0.17-0.19) in Australian-born women. Over 17 years, there were significant reductions in HBV prevalence among all women (from 0.88% in 2000 to 0.57% in 2016; P < .0001). Among women from high prevalence countries, the greatest absolute reductions were observed among those from Taiwan (10.1%, P < .001) followed by Tonga (5.4%, P < .001), whereas no reductions were observed for women born in Vietnam (P = .08), South Korea (P = .41) and Sudan (P = .06). In conclusion, routine antenatal HBV testing can be used to inform HBV prevalence estimates and vaccine programme impact in countries with limited surveillance and high migration to Australia., (© 2019 John Wiley & Sons Ltd.)

Background: Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up., Goals: Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up., Materials and Methods: We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases)., Results: The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60)., Conclusions: Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.

In a multicentre, genome-wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa-2a for ≥ 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post-treatment, using serological and/or virological endpoints. Thirty-six single-marker analyses and a gene-by-gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome-wide significance (P < 5 × 10 -8 ) in single-marker analyses, but suggestive associations (P < 1 × 10 -5 ) were identified for 116 SNPs. In gene-by-gene analyses, one gene, FCER1A (rs7549785), reached genome-wide significance (P = 2.65 × 10 -8 ) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 × 10 -7 ). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997)., (© 2019 John Wiley & Sons Ltd.)

In actual clinical practice, infinite nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B virus (HBV) infection is unrealistic. The most commonly used endpoint is suppression of HBV DNA to undetectable levels with normalization of alanine aminotransferase. However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing the hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cut-off value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cut-off value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1,716 patients were included in this review. When the HBsAg levels at EOT were <100 IU/mL and >100 IU/mL, the respective off-therapy virological relapse rates were 9.1%-19.6% (range) and 31.4%-86.8% (range) at ≥12 months off therapy, regardless of hepatitis B e antigen (HBeAg) status; the respective off-therapy clinical relapse rates were 15.4%-29.4% (range) and 48.1%-63.6% (range) at ≥12 months off therapy, regardless of HBeAg status; and the respective off-therapy HBsAg loss rates were 21.1%-58.8% (range) and 3.3%-7.4% (range) for HBeAg-negative patients at ≥39 months off therapy. Conclusion: Cessation of long-term NAs therapy before HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. An HBsAg level <100 IU/mL at EOT seems to be a useful marker for deciding when to discontinue NAs therapy. However, regular monitoring is required after the cessation of NAs treatment, and long-term outcomes must be further evaluated., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Our study aims to describe how obstetricians manage pregnant women infected with chronic hepatitis B in a region with a large high-risk population., Methods: We performed a cross-sectional study among practicing obstetricians in Santa Clara County, California. All obstetricians practicing in Santa Clara County were invited to participate in the study. Obstetricians were recruited in person or by mail to complete a voluntary, multiple choice survey on hepatitis B (HBV). Survey questions assessed basic HBV knowledge and obstetricians' self-reported clinical practices of the management of HBV-infected pregnant women. Pooled descriptive analyses were calculated for the cohort, as well as, correlation coefficients to evaluate the association between reported clinical practices and hepatitis B knowledge., Results: Among 138 obstetricians who completed the survey, 94% reported routinely testing pregnant women for hepatitis B surface antigen (HBsAg) with each pregnancy. Only 60.9% routinely advised HBsAg-positive patients to seek specialist evaluation for antiviral treatment and monitoring and fewer than half (48.6%) routinely provided them with HBV information. While most respondents recognized the potential complications of chronic HBV (94.2%), only 21% were aware that chronic HBV carries a 25% risk of liver related death when left unmonitored and untreated, and only 25% were aware of the high prevalence of chronic HBV in the foreign-born Asian, Native Hawaiian and Pacific Islander population. Obstetricians aware of the high risk of perinatal HBV transmission were more likely to test pregnant women for HBV DNA or hepatitis B e-antigen in HBV-infected women (r = 0.18, p = 0.033). Obstetricians who demonstrated knowledge of the long-term consequences of untreated HBV infection were no more likely to refer HBV-infected women to specialists for care (r = 0.02, p = 0.831)., Conclusion: Our study identified clear gaps in the practice patterns of obstetricians that can be readily addressed to enhance the care they provide to HBV-infected pregnant women.

It is well appreciated that ethnicity influences the natural history and immune responses during a chronic hepatitis B infection. In this study, we explore the effect of ethnicity and treatment cessation on Hepatitis B surface Antigen (HBsAg) seroclearance in patients with Nucleos(t)ide Analogue (NA)-induced Hepatitis B e Antigen (HBeAg) seroconversion. We performed a multi-ethnic, multicentric observational cohort study. The analyzed cohort consisted of 178 mono-infected, predominantly male (75.3%) chronic hepatitis B patients of mixed ethnicity (44.4% Asians, 48.9% Caucasians) with nucleos(t)ide analogue-induced HBeAg seroconversion. Treatment was withdrawn in 105 patients and continued in 73, leading to HBsAg loss in 14 patients off- and 16 patients on-treatment, respectively. Overall, HBsAg loss rates were not affected by treatment cessation (hazard ratio 1.45, p = 0.372), regardless of consolidation treatment duration. Caucasian ethnicity was associated with an increased chance of HBsAg loss (hazard ratio 6.70, p = 0.001), but hepatitis B virus genotype was not ( p = 0.812). In conclusion, ethnicity is the most important determinant for HBsAg loss after NA-induced HBeAg seroconversion, with up to six-fold higher HBsAg loss rates in Caucasians compared to Asians, irrespective of treatment cessation and consolidation treatment duration., Competing Interests: T. Vanwolleghem is recipient of a 2014 mandate from the Belgian Foundation Against Cancer (mandate number: 2014-087) and received research funding from Gilead Sciences, Bristol-Myers-Squib (BMS) and Roche Diagnostics. C. Moreno acted as consultant and received research grants from BMS and Gilead. H. Van Vlierberghe received research grants from Gilead and BMS. B. Hansen has received grants from and is consultant for Intercept Pharmaceuticals. H.L.A. Janssen has received grants from and is consultant for Abbott, Bristol-Myers Squibb, Gilead Sciences, Merck, Novartis, Roche, and Janssen. S. Van Hees, H. Chi, S. Bourgeois, T. Sersté, S. Francque, D. Wong, D. Sprengers and F. Nevens declare no conflicts of interest.

Background: Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial., Methods: The retrospective cohort study of 1224 Asian chronic hepatitis B (CHB) patients greater than 18 years without baseline osteopenia/osteoporosis seen at four US centers from 2008 to 2016. Patients were categorized into three groups-treatment-naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until the development of osteopenia/osteoporosis or end of the study., Results: Of the 1224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs 16.3% for TDF and 17.6% for ETV; P < 0.001). The 8-year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV, and 10.17% for untreated patients, with no statistically significant difference among the three groups ( P = 0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.34 and 1.59) nor ETV (adjusted HR = 0.98; 95% CI: 0.51 and 1.90) were associated with increased osteopenia/osteoporosis risk compared with untreated patients., Conclusions: Our retrospective study suggests that there is no significant increase in the incidence of osteopenia/osteoporosis for patients with CHB treated with TDF or ETV during a median follow-up of about 4 to 5 years. However, further study with longer follow-up is needed as an anti-HBV therapy, which is often lifelong or long-term and the development of osteopenia/osteoporosis can be a slow process., (© 2019 Wiley Periodicals, Inc.)

Objectives: To investigate risk factor patterns and the simultaneous occurrence of multiple risk factors in the viral, metabolic and lifestyle domains among Asian Americans, who have had the highest mortality rates from hepatocellular carcinoma (HCC)., Setting: Sacramento County, California, USA., Participants: Eligible participants were county residents ages 18 and older who had not been screened for chronic hepatitis B virus (HBV) and were born in a CDC-defined endemic area or whose parent was born in that area. Of 1004 enrolled, 917 were foreign-born Chinese (130 women, 94 men), Hmong (133 women, 75 men), Korean (178 women, 90 men) or Vietnamese (136 women, 81 men) with complete risk factor data., Primary and Secondary Outcome Measures: We tested participants for HBV and chronic hepatitis C virus (HCV); measured haemoglobin A1c and waist circumference; and recorded self-reported history of diabetes, hypertension, alcohol use and smoking status. We identified risk factor patterns using cluster analysis and estimated gender-specific age-standardised prevalence rates., Results: We identified four patterns: (1) viral (chronic HBV or HCV); (2) lifestyle (current smoker or alcohol user, no viral); (3) metabolic (≥2 metabolic, no lifestyle or viral); and (4) lower risk (≤1 metabolic, no lifestyle or viral). Vietnamese men (16.3%, 95% CI 7.4% to 25.3%) and Hmong women (15.1%, 95% CI 7.8% to 22.5%) had the highest viral pattern prevalence. Hmong women had the highest metabolic (37.8%, 95% CI 29.8% to 45.9%), and Vietnamese men the highest lifestyle (70.4%, 95% CI 59.1% to 81.7%) pattern prevalence. In multiple domains, Hmong men and women were most likely to have viral+metabolic risk factors (men: 14.4%, 95% CI 6.0% to 22.7%; women: 11.9%, 95% CI 5.6% to 18.3%); Vietnamese men were most likely to have lifestyle+viral (10.7%, 95% CI 2.7% to 18.8%), and lifestyle+metabolic but not viral (46.4%, 95% CI 34.4% to 58.5%) risk factors., Conclusions: Efforts to reduce HCC must comprehensively address multiple risk factors., Trial Registration Number: NCT02596438., Competing Interests: Competing interests: MSC served as a consultant to Gilead Sciences in 2016-18., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sweden has traditionally been considered a country with a low incidence of hepatocellular carcinoma (HCC). However, the increasing number of immigrants from areas with a high incidence of HCC might affect the number of HCC patients in Sweden. Aim: To examine trends in the incidence, treatment and overall survival of patients with HCC and an underlying liver disease (ULD) from a restricted, well-defined region of Sweden, between 2000 and 2014. Patients and methods: Nine hundred and eight patients with HCC were identified. Subjects were grouped into 5-year periods, and analysed for HCC diagnosis, ULD, staging and treatment selection in populations born outside Sweden versus non-immigrants and patient survival. The regions were Africa, Asia, EU-28 together with America and the Nordic countries, eastern Europe and Sweden. Results: Over the time periods, the patients with HCC and ULD increased. More patients from Africa had HCC and ULD than what would have been expected based on the number of immigrants from this region and they were also significantly younger than Sweden-born patients. For patients from Africa, Asia and eastern Europe; viral hepatitis was dominating ULDs. Patients from Africa, Asia and eastern Europe were subjected to liver transplantation (LT) in higher proportions than patients from Sweden. The survival rate for patients from eastern Europe was significantly better. Conclusions: Immigration increased the incidence of HCC and the need for active treatment such as LT. This fact raises the question of whether immigrants from regions with a high incidence of HCC ought to be subjected to mandatory hepatitis B and C virus (HBV and HCV) diagnosis and consequent liver ultrasounds for diagnosis of occult HCC. With such strategies, the morbidity and mortality of HCC could be reduced.

Background: Single nucleotide polymorphisms (SNPs) in the sodium taurocholate co-transporting polypeptide (NTCP) have been showed to be associated with natural history of hepatitis B virus (HBV) infection. However, it is unclear whether the SNPs are related to the clinical outcome of HBV infection in Thai individuals., Methods: The rs2296651 and rs4646287 polymorphisms of NTCP were determined by allelic discrimination using commercial TaqMan probes in blood samples of 1021 Thai individuals. These subjects included 610 patients with chronic HBV infection [CHB, 305 with hepatocellular carcinoma (HCC) and 305 without HCC], 206 subjects with spontaneous HBV clearance and 205 healthy controls who were age and gender-matched., Results: The frequencies of rs2296651 A minor allele in the CHB group, the HBV clearance group and healthy controls were 7.8, 7.3 and 13.9%, respectively. For rs4646287, the frequencies of T minor allele of the corresponding groups were 10.4, 8.0 and 9.5%, respectively. Compared with healthy controls, the frequencies of rs2296651 GA + AA genotypes were significantly lower in the CHB group (P &lt; 0.001) and in the HBV clearance group (P = 0.001). There was no difference in their distribution between the HBV clearance and CHB groups. Among the CHB group, the distribution of GA + AA genotypes in patients with HCC were significantly lower than in patients without HCC (P = 0.014). The frequencies of HBeAg positivity in patients harboring GG and GA + AA genotypes were 39.8 and 23.5%, respectively (P = 0.004). Among patients with HCC, the mean HBV DNA of the corresponding genotypes were 4.9 ± 1.3 vs. 2.7 ± 1.0 log 10 IU/mL, respectively (P &lt; 0.001). There was no difference in genotype and allele frequencies of rs4646287 polymorphism among all studied groups., Conclusions: Our results showed that rs2296651 polymorphism was associated with a decreased risk of susceptibility to HBV infection and the development of HCC. These data suggest that the NTCP polymorphism might have an influence on natural history of HBV infection in Thai individuals. This abstract was partly presented at the American Association for the Study of Liver Diseases (AASLD) Meeting 2018, November 9-13, 2018, in San Francisco, CA, USA and was published in Hepatology 2018; 68:1237A-1238A.

Objective: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment., Background: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients., Patients and Methods: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8-54.6 months)., Results: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22 IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation., Conclusion: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis.

Background: Hepatitis B virus (HBV) genotype E is a poorly studied genotype that almost exclusively occurs in African people. It seems to harbour intrinsic potential oncogenic activity and virological characteristics of immune scape but a paucity of information is available on clinical and virological characteristic of HBV genotype E-infected patients as well as on the efficacy of anti-HBV drugs for such patients. The increasing flow of migrants from high endemic HBV sub-Saharan Africa, where genotype E is the predominant one, to Western countries makes improving such knowledge critical in order to deliver proper medical care., Methods: Prospective observational study of naïve patients of sub-Saharan origin treated for chronic HBV genotype E infection at a Tropical Medicine clinic sited in Spain from February 2004 to January 2018. The aim of the study was to describe the response of chronic HBV genotype E infection to nucleos(t)ide analogues (NA), entecavir or tenofovir, in real clinical practice., Results: During the study period, 2209 sub-Saharan patients were assisted at our Tropical Medicine Unit and 609 (27.6%) had chronic HBV (CHB) infection. Genotype information was available for 55 naïve patients initiating treatment with NA (entecavir or tenofovir), 43 (84.3%) of them being genotype E, although 15 were excluded because they did not meet study inclusion criteria. Thus, a total of 28 CHB genotype E patients were included and followed for 24 months at least. Twenty-one patients were in HBeAg-negative chronic hepatitis phase and 7 patients in HBeAg-positive chronic hepatitis phase. After one year of treatment, among those with good adherence, 89.4% (17/19) of the HBeAg-negative patients and 80% of the HBeAg-positive ones had undetectable viral loads. Response rates reached 100% in both groups after 15-18 months of follow-up. Out of the 7 HBeAg-positive patients, 6 (85.7%) presented HBeAg loss in a median time of 31.8 months. Neither serious adverse effects nor hepatocarcinoma cases happened during the study period., Conclusions: HBV genotype may influence disease progression and antiviral response. Our study provides precious information on the efficacy and safety of NA treatment for CHB genotype E infection, a fairly unknown genotype with and increasing epidemiological impact.

Introduction and Aim: Hepatitis B virus (HBV) infection remains a public health problem worldwide. In addition, HBV infection results are influenced by various virological, immunological, and genetic factors. Inducible T-cell costimulator (ICOS) polymorphisms involving chronic HBV infection have been confirmed in previous studies. This study was to explore the effects of ICOS single nucleotide polymorphisms in HBV subtypes and their interactions with viral mutations on HBV infection outcomes., Material and Methods: A total of 1,636 Han Chinese individuals were recruited, including 47 asymptomatic HBV carriers (ASC), 353 chronic hepatitis B (CHB) patients, 327 HBV-related liver cirrhosis (LC) patients, 193 HBV-related hepatocellular carcinoma (HCC) patients, 464 patients with spontaneous recovery from HBV infection (SR), and 252 healthy controls (HC). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931, and rs4675379). Direct sequencing was used to determine the HBV mutations in the enhancer II, basal core promoter, and pre-core regions., Results: We found that the genotype "TC" of ICOS rs10932029 SNP was associated with decreased HBV-related LC risk in the genotype C group. Additionally, the A1762T, G1764A and A1762T/G1764A mutations were associated with an increased risk of LC in the genotype C group. Further study indicated that interactions between ICOS rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations significantly decreased the LC risk in the genotype C group., Conclusion: The rs10932029 genotype "TC" might be an LC-protective factor for HBV genotype C infection. The interactions between the rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations could decrease the risk of LC.

Background & Aims: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied trends in age-standardized mortality of chronic liver diseases in adults at least 20 years old in the United States from 2007 through 2016., Methods: We collected data from the US Census and National Center for Health Statistics mortality records and identified individuals with HCV infection, ALD, nonalcoholic fatty liver disease, or hepatitis B virus infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC)., Results: Age-standardized HCV-related mortality increased from 7.17 per 100,000 persons in 2007 to 8.14 per 100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09 per 100,000 persons in 2014 to 7.15 per 100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014 but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC 2.3% from 2007 through 2013 and APC 5.5% from 2013 through 2016) and nonalcoholic fatty liver disease (APC 6.1% from 2007 through 2013 and APC 11.3% from 2013 through 2016). Mortality related to hepatitis B virus decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI -3.0 to -1.2). Etiology-based mortality in minority populations was higher. HCV-related mortality (per 100,000 persons) was highest in non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest in non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for hepatitis B virus infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks and 0.47 for non-Hispanic whites)., Conclusion: In our population-based analysis of chronic liver disease mortality in the United States, the decrease in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, whereas mortality from ALD and nonalcoholic fatty liver disease increased during the same period. Minorities in the United States have disproportionately higher mortality related to chronic liver disease., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the cultural and linguistic diversity in Australians currently living with chronic hepatitis B (CHB), the majority of whom were born overseas, and to identify trends in this diversity over time., Methods: Estimates were generated by combining Australian census country of birth information with seroprevalence data generated from antenatal serology linked with surveillance notifications. The number of people living with CHB was assessed according to country of birth using the 2011 and 2016 censuses., Results: The total number of Australian residents living with CHB increased by 20% between 2011 and 2016, substantially outpacing population growth. The most common country of birth continued to be China, with the number of Chinese-born Australians living with CHB increasing by 60% in the 5-year period. Decreased numbers were observed for people born in European countries., Conclusions: The epidemiology of chronic hepatitis B in Australia has shifted over time due to changing migration patterns, with increases in many countries in the Asia-Pacific, African and Middle Eastern regions. Implications for public health: Interventions to improve the health of people living with CHB are imperative, and these up-to-date estimates identify priority groups and communities, which are constantly changing., (© 2018 The Authors.)

Background: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated., Aims: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect., Methods: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined., Results: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ., Conclusion: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects., (© 2018 John Wiley & Sons Ltd.)

Background: Long-term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)-related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma (HCC) development., Aims: To define the clinical features and outcomes of HCC in long-term NUC-treated HBV patients., Methods: All HCCs developing between 2005 and 2016 in NUC-treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied., Results: Seventy-six HCC patients were included. Median age was 67 (40-83) years, 84% males, 96% Caucasian, 95% HBeAg-negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1-3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6-57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first-line treatment, in 3 after the second-line treatment, in 2 after the third-line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7-144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3-53) months, and the cumulative 5-year liver-related survival was 74%., Conclusions: HCCs developing in patients under long-term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5-year survival rates., (© 2018 John Wiley & Sons Ltd.)

Background & Aims: It has yet to be firmly established whether host IFNL3 (IL28B) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the IFNL3 region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies., Methods: Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment). Associations between treatment response and the number of copies of the poor-response allele at three SNPs (rs8099917, rs12980275, rs12979860) were explored with logistic regression models in Asian and white patients., Results: The HBeAg-positive and -negative populations comprised 465 (92% Asian, 50% HBV genotype C) and 236 (79% Asian, 41% HBV genotype C) patients, respectively, and had respective response rates of 26% and 47%. The IFNL3 genotype was strongly associated with ethnicity. There was no association between IFNL3 genotype and treatment response in HBeAg-positive or -negative patients. Independent predictors of treatment response were: sex, HBV DNA level and alanine aminotransferase level in HBeAg-positive Asian patients; age in HBeAg-negative Asian patients; and HBV DNA in HBeAg-negative white patients., Conclusions: This is the largest analysis to date of associations between IFNL3 genotype and peginterferon response in patients with chronic hepatitis B. The data suggest that IFNL3 polymorphism is not a major determinant of the response to peginterferon alfa-2a in either HBeAg-positive or HBeAg-negative patients., Competing Interests: LW has received fees for serving as a speaker, consultant, and advisory board member for AbbVie, Bristol-Myers Squibb (BMS), Gilead, Johnson & Johnson (J&J), and GlaxoSmithKline (GSK) within the last 3 years. Additional funding for the study was provided to LW by the China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period. HW has received grant/research support from Abbott, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics, and Siemens, and has received consulting fees and has been an advisory board and speakers’ bureau member for Abbott, AbbVie, Biolex, BMS, Boehringer Ingelheim, Eiger Pharmaceuticals, Falk Foundation, Gilead, IST, J&J/Janssen-Cilag/Janssen TE, Medgenics, Merck/Schering-Plough, Novartis, Novira, Roche, Roche Diagnostics, Siemens, Transgene, and ViiV. Y-FL has served as an advisory board member for Roche. HL-YC has received fees for serving as a speaker and advisory board member for Roche, BMS, Gilead, Novartis, and MSD, and as a speaker for Echosens and GSK, and has received an unrestricted grant for HBV research from Roche. TP has received grant/research support from BMS, Roche, MSD, Novartis, Fibrogen, and Bayer, and has been a member of advisory boards or speakers’ bureaux for BMS, Roche, MSD, Novartis, and GSK. JJ has received fees for serving as a speaker, consultant, and advisory board member for BMS, MSD, Novartis, and Roche within the last 3 years. MRB has been a member of speakers’ bureaux for BMS, Gilead, Roche, and Janssen, and has been a member of advisory boards for AbbVie, Roche, Gilead, and MSD. MD has been a member of speakers’ bureaux for Roche, MSD, AbbVie, BMS, Gilead, and Janssen. SG has received fees as a member of advisory boards and speakers’ bureaux for Roche, BMS, Gilead, Janssen, and MSD. YZ has been a Genentech/Roche employee and has owned Roche stock and options. HH and CW are employees of Roche and declare stock ownership. BS has received fees for serving as a consultant/contract statistician for Roche, through BStats Solutions Ltd, from March 2013 to the present. AJT has received grant funding from AbbVie, Gilead Sciences, BMS, and Merck, has received consultancy fees from AbbVie, Gilead Sciences, BMS, Roche Diagnostics, Merck, and Spring Bank Pharmaceuticals, and has provided sponsored lectures (national or international) for AbbVie, Roche Diagnostics, Gilead Sciences, BMS, and Merck. The China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period provided support in the form of salaries to HH, YZ, CW, and BS. This does not alter our adherence to PLOS ONE policies on sharing data and materials. This study was funded in part by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Peginterferon alfa-2a (PEGASYS®) is marketed worldwide by F Hoffmann-la Roche Ltd, Basel, Switzerland.

Background: In Australia's Northern Territory, the hepatitis B virus (HBV) subgenotype A2 (subtype adw2) vaccine was introduced in 1988 for Indigenous infants. Subsequently, the circulating viral genotype has been identified as subgenotype C4 (subtype ayw3). We assessed HBV vaccine effectiveness (VE) in light of this subtype mismatch., Methods: Participants of the Aboriginal Birth Cohort (ABC) study were recruited at birth (1987-1990), with HBV serology obtained at follow-up waves 3 (2005-2007) and 4 (2013-2015). Participants were immune if HBV surface antibody levels exceeded 10 IU/L. We determined the VE against any HBV infection (anti-HBc + ) and against chronic infection (HBsAg + or HBV DNA + ), comparing non-vaccinated participants with those fulfilling United States Centers for Disease Control and Prevention (CDC) criteria for full HBV immunisation., Results: Of 686 participants in the ABC study, we obtained HBV serology from 388 at wave 4. 181 participants were immune to HBV and 97 had evidence of any infection. Seven participants were chronically infected, of whom five had received three vaccine doses, and anti-HBc seroconversion had occurred subsequent to the three vaccine doses for two of these seven participants. Comparing the 107 participants who had been vaccinated in accordance with CDC recommendations and 127 who had not been vaccinated, VE against any infection was 67% (95%CI, 43-104%). The odds of being anti-HBc + was 87% lower in participants raised in urban settings compared to those born into families from remote areas (OR, 0.1; 95%CI, 0.03-0.4)., Conclusions: In a setting where there exists a subtype mismatch between vaccine and circulating genotype, the vaccine was largely effective in preventing chronic infection but sub-optimal against any infection. The implications of a high prevalence of anti-HBc seropositivity in this population are unclear and require further study. The fact that anti-HBc seropositivity was strongly associated with remote dwelling suggests ongoing viral exposure in remote settings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Both in France and in Italy hepatitis B is present mostly among the migrant population coming from sub-Saharan Africa and mainly among those migrants having a poor socio-economic background. This article is aimed at assaying the impact of public policies adopted by France and Italy for migrants' health on the treatment of migrants with HBV. The article is based on semi-structured interviews conducted with 30 immigrant adults taken into care by two associations dealing with medical, psychological and social issues of immigrants applying for a residence permit, mainly asylum seekers. The results of this study bring to light specific difficulties relating to national contexts, to the type of HBV (inactive or active) and to the administrative situation of the migrants. In France irregular migrants are screened in humanitarian associations. In Italy the screening is done in public hospitals. In both countries, only migrants suffering from chronic hepatitis B obtain a residence permit for medical reasons. More migrants in Italy than in France abandon HBV treatment. This study describes how specific national immigration and health policies impact in a different way the therapeutic and social path of migrants suffering from hepatitis B. The analysis provides useful material for the development of strategies to prevent and control hepatitis B among the migrant population. It also shows how social determinants affect migrants' health more than values or cultural factors do.

African-Australians have a high prevalence of chronic hepatitis B (CHB) and an increased risk of liver cancer (hepatocellular carcinoma, HCC) at a younger age than other affected groups living with CHB. The prevention of HCC-related mortality is possible with timely diagnosis of CHB, regular monitoring including liver cancer surveillance and appropriate treatment with antiviral therapy. Currently, little is known about how African-Australians living with CHB understand their condition, their risk of liver cancer and the need for regular monitoring. There were 19 semi-structured interviews conducted with African-Australians who have CHB. The interviews explored the participants' knowledge of CHB, their perceptions of future health risks and experiences and understanding of healthcare. The three major themes identified in the analysis were (i) the risks to physical health including liver cancer, (ii) risks to social and emotional wellbeing from diagnosis and disclosure and (iii) the fear and worry associated with being infectious. The understanding of risk and mitigation of that risk was framed by their understanding of health, ageing, as well as participants' educational background and faith. Our findings show the importance of engagement with the broader social and emotional effects of CHB by clinicians and services, and can assist in developing interventions to increase participation in healthcare, including liver cancer surveillance.

Background: Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3'UTR of STAT3 and chronic HBV infection has yet to be investigated., Methods: This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection resolvers, and 169 healthy controls. STAT3 rs1053004 and rs1053005 polymorphisms were genotyped by TaqMan SNP Genotyping Assays., Results: The rs1053004 genotype CC [P value by Bonferroni correction (P c ) = 0.002] and allele C (P c  = 0.019) were more frequent in patients with chronic HBV infection than in healthy controls. The rs1053005 genotype GG was also more frequent in patients with chronic HBV infection than in healthy controls (P c  = 0.046). The rs1053004-rs1053005 haplotype T-G was less frequent in patients with chronic HBV infection than in healthy controls (P c  < 0.001). Haplotype C-A was more frequent in patients with liver cirrhosis than in patients with HCC (P c  = 0.042). The rs1053004 genotype TC, rs1053005 genotype AG and rs1053004-rs1053005 haplotype T-A were associated with higher HBV DNA levels., Conclusions: STAT3 rs1053004 and rs1053005 polymorphisms and haplotypes formed by rs1053004 and rs1053005 are associated with chronic HBV infection and the haplotypes appear to be also associated with the development of liver disease. Studies in large sample sizes of patients and control populations are required to verify and extend these findings.

Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10-27) copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the cause of viral replication persistence. Moreover, a fair percentage of stop codon mutations were found. The lack of correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in these subjects suggests a pathway of virus production that is not linked to HBsAg secretion. Studies with a larger number of patients with CHB due to the E genotype are advisable to corroborate these observations.

Purpose: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC. Experimental Design: GWAS scan is performed in a collection of 205 HBV-related HCC trios (each trio includes an affected proband and his/her both parents), and 355 chronic HBV carriers with HCC (cases) and 360 chronic HBV carriers without HCC (controls), followed by two rounds of replication studies totally consisting of 3,796 cases and 2,544 controls. Results: We identified a novel association signal within the CDK14 gene at 7q21.13 (index rs10272859, OR = 1.28, P = 9.46 × 10 -10 ). Furthermore, we observed that the at-risk rs10272859[G] allele was significantly associated with higher mRNA expression levels of CDK14 in liver tissues. Chromosome conformation capture assays in liver cells confirmed that a physical interaction exists between the promoter region of CDK14 and the risk-associated SNPs in strong linkage disequilibrium with the index rs10272859 at 7q21.13. This index rs10272859 also showed significant association with the survival of HCC patients. Conclusions: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. Clin Cancer Res; 24(4); 906-15. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background & Aims: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown., Methods: A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients., Results: Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542., Conclusions: This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

Hepatitis B virus (HBV) infection is more common in African Americans than in white Americans. We compared the epidemiologic, clinical, and virological characteristics of US-born African Americans (USAAs) to those of foreign-born African Americans (FBAAs) with chronic hepatitis B. The adult cohort study of the Hepatitis B Research Network enrolls patients with HBV infection from 21 clinical sites in the United States and Canada. A total of 237 (15%) of the adult participants with chronic HBV infection that were enrolled from January 20, 2011, to October 2, 2013, were of African descent, including 57 USAAs and 180 FBAAs (76%). Compared with FBAAs, USAAs were older and more likely to have acquired HBV through sexual exposure, to be HBeAg-positive, to have higher HBV DNA levels, and to be infected with HBV genotype A2. FBAAs from West Africa were more likely to have elevated serum alanine aminotransferase (72% vs. 50%; P < 0.01) and higher HBV DNA levels (median, 3.2 log10 IU/mL vs. 2.8 log10 IU/mL; P = 0.03) compared with East African FBAAs. The predominant HBV genotype among West African FBAAs was E (67%), whereas genotypes A (78%) and D (16%) were common in East African FBAAs. Significant differences were found between USAAs and FBAAs, highlighting the need for tailored strategies for prevention and management of chronic HBV infection for African Americans., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic hepatitis B virus (HBV) infection is highly prevalent worldwide and is most often diagnosed through screening efforts. In order to identify the specific ethnic groups at greatest risk, it is necessary to go beyond traditional categories. We conducted a retrospective case series in a primary care clinic serving non-English speaking immigrants to determine the prevalence of HBV among patients of various primary spoken languages (used as a proxy for ethnicity). Among the 1378 patients, the overall prevalence of current infection was 8%. HBV infection was markedly higher among Somali, Oromo and Khmer speakerscompared to other groups. This study illustrates the use of granular language data in describing the serologic profiles of HBV infection among non-English speaking patients in primary care setting. The variations in prevalence by language have implications for public health HBV screening efforts, in addition to suggesting potential risk factors for transmission.