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Purpose: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors., Methods: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world., Results: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided., Conclusion: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Importance: Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited., Objective: To examine whether HBV treatment initiation and outcomes differ among racial groups., Design, Setting, and Participants: From January 14, 2011, to January 28, 2018, hepatitis B surface antigen-positive adults (age ≥18 years) not receiving anti-HBV therapy were enrolled and followed up at weeks 12, 24, and every 24 weeks thereafter in a multicenter longitudinal cohort study (Hepatitis B Research Network [HBRN] adult cohort study) conducted in North America. The last study visit and data collection were completed January 28, 2019. Data were analyzed from August 27, 2021, to August 25, 2022. All HBRN participants were included unless they had acute HBV, HIV, hepatitis C or D, less than 24-weeks of follow-up after enrollment, initiated treatment at or immediately after enrollment, or had unknown race., Exposures: Participants had clinical and laboratory assessments and could receive anti-HBV treatment after enrollment., Main Outcomes and Measures: Hepatitis B virus treatment initiation and major adverse liver outcomes (hepatic decompensation, hepatocellular carcinoma, liver transplant, and death)., Results: Of 1550 participants, 193 (12%) were African American or Black, 1157 (75%) were Asian, 157 (10%) were White, and 43 (3%) were other races; 789 (51%) were women, and the median age was 41.2 (IQR, 32.9-51.6) years. Sociodemographic and virologic parameters differed between groups. During 5727 person-years of follow-up, 504 participants initiated treatment, with incidences of 4.8 per 100 person-years in African American or Black individuals, 9.9 per 100 person-years in Asian individuals, 6.6 per 100 person-years in White individuals, and 7.9 per 100 person-years in those of other races (P < .001). A lower proportion (14%) of African American or Black participants met treatment criteria compared with Asian (22%) and White (27%) individuals (P = .01). The cumulative probabilities of treatment initiation after meeting the criteria were not significantly different among racial groups (African American or Black, 0.45; Asian, 0.38; White, 0.40 at 48 weeks and African American or Black, 0.45; Asian, 0.51; White, 0.51 at 72 weeks; P = .68). The incidence of major adverse liver outcomes was 0.1 per 100 person-years and did not differ by race., Conclusions and Relevance: In this observational study of chronic HBV, African American or Black participants were less likely than individuals of other races to meet treatment criteria, but among those who did, HBV treatment receipt did not differ significantly by race or socioeconomic factors. Not all eligible participants initiated treatment, but adverse liver outcomes were rare. These findings may not be generalizable to patients with chronic HBV receiving care in other settings.

Background and Aim: The etiology of liver diseases has changed in recent years, but its impact on the comparative burden of liver cancer between males and females is unclear. We estimated sex differences in the burden of liver cancer across 204 countries and territories from 2010 to 2019., Approach and Result: We analyzed temporal trends in the burden of liver cancer using the methodology framework of the 2019 Global Burden of Disease study. We estimated annual frequencies and age-standardized rates (ASRs) of liver cancer incidence, death, and disability-adjusted life-years (DALYs) by sex, country, region, and etiology of liver disease. Globally in 2019, the frequency of incident cases, deaths, and DALYs due to liver cancer were 376,483, 333,672, and 9,048,723 in males, versus 157,881, 150,904, and 3,479,699 in females. From 2010 to 2019, the incidence ASRs in males increased while death and DALY ASRs remained stable; incidence, death, and DALY ASRs in females decreased. Death ASRs for both sexes increased only in the Americas and remained stable or declined in remaining regions. In 2019, hepatitis B was the leading cause of liver cancer death in males, and hepatitis C in females. From 2010 to 2019, NASH had the fastest growing death ASRs in males and females. The ratio of female-to-male death ASRs in 2019 was lowest in hepatitis B (0.2) and highest in NASH (0.9)., Conclusions: The overall burden of liver cancer is higher in males, although incidence and death ASRs from NASH-associated liver cancer in females approach that of males., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high-risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow-up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53-2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26-13.07, p < 0.001). Mean total and patient-paid daily surveillance-related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance-related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy-to-implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota., Aim: To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program., Methods: We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards, community clinics and local mosques between November 2010 and December 2015 (data was analyzed in 2020). Serum was tested for hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody and anti-HCV antibody., Results: Of 779 participants, 15.4% tested positive for chronic HBV infection, 50.2% for prior exposure to HBV and 7.6% for chronic HCV infection. Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5% and 11.6%; for prior exposure to HBV were 44.8% and 41.3%; and for chronic HCV were 6.7% and 5.7%, respectively. Seven participants developed incident HCC during follow up., Conclusion: Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants, with prevalence of both infections substantially higher than in the general United States population. Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The integration of viruses into the human genome is known to be associated with tumorigenesis in many cancers, but the accurate detection of integration breakpoints from short read sequencing data is made difficult by human-viral homologies, viral genome heterogeneity, coverage limitations, and other factors. To address this, we present Exogene, a sensitive and efficient workflow for detecting viral integrations from paired-end next generation sequencing data. Exogene's read filtering and breakpoint detection strategies yield integration coordinates that are highly concordant with long read validation. We demonstrate this concordance across 6 TCGA Hepatocellular carcinoma (HCC) tumor samples, identifying integrations of hepatitis B virus that are also supported by long reads. Additionally, we applied Exogene to targeted capture data from 426 previously studied HCC samples, achieving 98.9% concordance with existing methods and identifying 238 high-confidence integrations that were not previously reported. Exogene is applicable to multiple types of paired-end sequence data, including genome, exome, RNA-Seq and targeted capture., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC., Methods: We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre., Results: Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤ .04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P < .0001) and undergo HCC treatment with curative intent (P = .003). Propensity-score matching on HCC diagnosis year, gender and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P = .43) and among patients with cirrhosis (P = .57). Among patients without cirrhosis, non-Asians had poorer 5-year survival compared with Asians (37.6% vs 53.7%, P = .01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co-infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07-3.74], P = .03)., Conclusion: Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although hepatitis B virus (HBV) integration into the cellular genome is well known in HCC (hepatocellular carcinoma) patients, its biological role still remains uncertain. This study investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) alterations in paired tumor and non-tumor tissues. Compared to those in non-tumors, tumoral integrations occurred less frequently but with higher read counts and were more preferentially observed in genic regions with significant enrichment of integration into promoters. In HBV-related tumors, TERT promoter was identified as the most frequent site (38.5% (10/26)) of HBV integration. TERT promoter mutation was observed only in tumors (24.2% (8/33)), but not in non-tumors. Only 3.00% (34/1133) of HBV integration sites were shared between tumors and non-tumors. Within the HBV genome, HBV breakpoints were distributed preferentially in the 3' end of HBx, with more tumoral integrations detected in the preS/S region. The major genes that were recurrently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tumors. Functional enrichment analysis of tumoral genes with integrations showed enrichment of cancer-associated genes. The patterns and functions of HBV integration are distinct between tumors and non-tumors. Tumoral integration is often enriched into both human-virus regions with oncogenic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcinogenesis.

Background/aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance., Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated., Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC., Conclusion: The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

Background & Aims: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non-viral causes of HCC, particularly non-alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC., Methods: We conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878)., Results: Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV-related HCC (HBV-HCC) (P = .001) and 85.9% of HCV-HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five-year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV-HCC patients and 27.7% among HCV-HCC patients (P < .001 for both by the log-rank test). HCC aetiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were., Conclusions: Compared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumours at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite chronic Hepatitis B virus (HBV) infection being the main cause of younger-onset complex liver disease including cirrhosis and hepatocellular carcinoma (HCC) in Africa, very little is known regarding the seroprevalence of HBV in the Gabonese general population. This investigation aimed to provide strong epidemiological data and risk factors associated with HBV infection in first-time blood donors representative of the urban adult population. The screening of HBsAg was carried out using 4th generation ELISA kits. The overall seroprevalence of HBsAg was 7.28%. The frequency of HBsAg was differential and marked by annual variations in blood donors from 2009 to 2016. Seroprevalence was 2-fold higher among males versus females (OR = 1.90 (95% CI: 1.75-2.06), P<0.001). HBsAg seroprevalence was significantly higher in donors of the age group 25-35 years old compared to donors of the age group <18 years (OR = 1.64 (95% CI: 1.03-2.60), P = 0.04). The seroprevalence of HBsAg in family/replacement donors (FRD) was significantly higher than that of voluntary non-remunerated donors (VNRD) (OR = 0.88 (95% CI: 0.83-0.94), P <0.001). The simultaneous comparison of HBsAg seroprevalence with blood donation type, gender and age showed that the higher prevalence in FRD was significant only in males between 18 and 45 years and in females between 25 and 34 years of age. This study confirms the high endemicity of HBV in Gabon while identifying the most infected age groups for both men and women.

ObjectivesTo test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles.Study designClinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers.ResultsChildren (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (

Background & aimsChronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.MethodsThe HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America.ResultsHalf of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range.ConclusionsThe HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America.

Background and Aim: Staining for hepatitis B viral antigens is often done in liver biopsies from patients with chronic hepatitis B, but its correlates with clinical phenotypes are not well described. Methods: Biopsies were collected from a large cohort of adults and children with chronic hepatitis B viral infection through the Hepatitis B Research Network. Immunohistochemical staining of sections was done for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and then centrally read by the pathology committee. The degree of liver injury and pattern of staining were then correlated with clinical characteristics, including the clinical phenotype of hepatitis B. Results: Biopsies from 467 subjects were studied, including 46 from children. Immunostaining for HBsAg was positive in 417 (90%) with scattered hepatocyte staining being the most common pattern. HBsAg staining correlated best with serum levels of HBsAg and hepatitis B viral DNA; the absence of HBsAg staining was often a prelude to loss of HBsAg from serum. HBcAg staining was positive in 225 (49%), and, while cytoplasmic staining was more frequent than nuclear staining, both nuclear and cytoplasmic positivity were often seen in the same specimen. Staining for HBcAg correlated with both level of viremia and liver injury. No biopsies from inactive carriers had stainable HBcAg, while 91% of the biopsies from those with hepatitis B e antigen‐positive chronic hepatitis B stained positively for HBcAg. Conclusion: Immunostaining for hepatitis B viral antigens may yield helpful insights into liver disease pathogenesis but appears to add little to commonly used serological and biochemical blood tests. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Antiviral treatment reduces the risk of HCC and mortality; nonetheless, globally in 2019, only 2.2% of CHB patients received treatment. Current international CHB guidelines recommend antiviral treatment only in subsets of patients with clear evidence of liver damage. This contrasts with hepatitis C or HIV where early treatment is recommended in all infected patients, regardless of end-organ damage. This narrative review aims to provide an overview of data on the early initiation of antiviral treatment and its related potential economic impact. Literature searches were performed using PubMed and abstracts from international liver congresses (2019–2021). Data on risk of disease progression and HCC and the impact of antiviral treatment in currently ineligible patients were summarized. Cost-effectiveness data on early antiviral treatment initiation were also collated. Accumulating molecular, clinical, and economic data suggest that early initiation of antiviral treatment could save many lives through HCC prevention in a highly cost-effective manner. In light of these data, we consider several alternative expanded treatment strategies that might further a simplified 'treatment as prevention' approach. [ABSTRACT FROM AUTHOR]

Liver-related diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), are significant causes of mortality globally. Specific causes and predictors of liver-related mortality in low resource settings require assessment to help inform clinical decision making and develop strategies for improved survival. The objectives of this study were to determine the proportion of liver-related deaths associated with liver cirrhosis, HCC, and their known risk factors, and secondly to determine predictors of in-hospital mortality among cirrhosis and HCC patients in Ghana. We first performed a cross-sectional review of death register entries from 11 referral hospitals in Ghana to determine the proportion of liver-related deaths and the proportion of risk factors associated with these deaths. Secondly, we conducted a retrospective cohort review of 172 in-patient liver cirrhosis and HCC cases admitted to a tertiary referral centre and determined predictors of in-hospital mortality using binary logistic regression and Kaplan-Meier survival analysis. In total, 8.8% of deaths in Ghanaian adults were due to liver-related causes. The proportion of liver-related deaths attributed to HBV infection was 48.8% (95% CI: 45.95–51.76), HCV infection was 7.0% (95% CI: 5.58–8.45), HBV-HCV co-infection 0.5% (95% CI: 0.1–0.9) and alcohol was 10.0% (95% CI: 8.30–11.67). Of 172 cases of HCC and liver cirrhosis, the in-patient mortality rate was 54.1%. Predictors of in-patient mortality in cirrhotic patients were increasing WBC (OR = 1.14 95% CI: 1.00–1.30) and the revised model for end-stage liver disease with sodium (MELD-Na) score (OR = 1.24 95% CI: 1.01–1.54). For HCC patients, female sex (OR = 3.74 95% CI: 1.09–12.81) and hepatic encephalopathy (grade 1) were associated with higher mortality (OR = 5.66 95% CI: 1.10–29.2). In conclusion, HBV is linked to a high proportion of HCC-related deaths in Ghana, with high in-hospital mortality rates that require targeted policies to improve survival. [ABSTRACT FROM AUTHOR]

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co‐infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24 weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24–48 weeks. HBeAg loss was defined as first HBeAg‐negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg‐negative values ≥24 weeks apart. During a median follow‐up of 1.8 years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8–13.3) per 100 person‐years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre‐core mutations versus wild type. Additionally, during follow‐up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies. [ABSTRACT FROM AUTHOR]

Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg‐positive CHB is associated with a liver disease spectrum ranging from none to severe. Aim: To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg‐positive CHB. Methods: A cross‐sectional analysis was conducted among HBV mono‐infected participants enrolled in Hepatitis B Research Network (HBRN) cohorts to explore clinical and virological associations with quantitative HBeAg (qHBeAg). Results: Among 763 HBeAg+ participants (56% female; 85% Asian; median age 26 years), multivariable median regression modelling significantly associated qHBeAg with liver injury (inverse qHBeAg association with ALT p<.001 and APRI p<.001), and with both race and age (p=0.01). Among Asians, qHBeAg was inversely related to age; a relationship less clear among Blacks and Whites. Among Asians also, median qHBeAg levels were higher among those infected with HBV genotype C versus B (p<0.001), suggesting causal virologic differences. Across all races, median qHBeAg was higher in women (p=.01). Independent of sex, age, race and HBV genotype, qHBeAg was higher in participants with predominant wild‐type versus basal core promoter and/or precore 'stop' viral variants (p<0.001). Conclusion: Lower qHBeAg was observed among HBRN participants with the greatest degree of liver injury independent of demographics and HBV genotype. These data support longitudinal studies to examine the role of qHBeAg in modulating the host immune response and predicting the outcomes of chronic HBV infection. [ABSTRACT FROM AUTHOR]

Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viraemia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analysed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B Research Network, long‐term natural history studies of chronic HBV infection. A cross‐sectional analysis examined factors associated with HBeAg positivity, including demographic and virologic data, across the age spectrum. Among 2241 enrolled participants who met criteria for this analysis, 825 (37%) were seropositive for HBeAg. The prevalence of HBeAg was lower in those with older age, ranging from 85% among those up to 10 years of age to only 12% among those older than 50 years. In addition to age, both race and HBV genotype were independently associated with HBeAg positivity. There was a significant interaction between age and race; the prevalence of HBeAg was significantly higher among Asians > 10‐30 years old vs Whites or Blacks who were >10 to 30 years old and those infected with HBV genotype C. Conversely, the presence of the basal core promoter and precore variants was associated with significantly lower prevalence of HBeAg, even when adjusted for age, race and genotype. These data will provide a better understanding of factors associated with seropositivity for HBeAg and may lead to better strategies for preventing HBV infection and broader indications for antiviral therapy. [ABSTRACT FROM AUTHOR]

Background & Aims: There are few data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival. Methods: This analysis included patients with HBV (n = 64) or HCV (n = 118) infection who were diagnosed with HCC at the Mayo Clinic in Rochester, Minnesota from 1994–2008; groups were matched for age and sex. The diagnosis of cirrhosis was based on histology and, if histologic information was insufficient or unavailable, clinical indicators that included ascites or varices, thrombocytopenia or splenomegaly, and radiographic configuration of cirrhosis. Virologic characteristics, tumor stage, and patient survival were also assessed. Results: The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P = .46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P = .24). Among HCV patients, 5.2% were negative for HCV RNA after antiviral treatment; 63.4% of HBV patients had HBV DNA <2000 IU/mL with or without treatment. Patients with HBV tended to have less surveillance and more advanced stages of HCC, without differences in survival from those with HCV infection (P = .75). Conclusions: Most patients with HCC and chronic viral hepatitis had evidence of cirrhosis, including those with HBV infection and those without active viral replication. [Copyright &y& Elsevier]

To evaluate the effect of hepatic steatosis on LI-RADS® major features at MRI in patients with non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC). HCC and liver parenchyma features at MRI from 48 consecutive patients with NAFLD and histology proven HCC (mean ± SD; 4.5 ± 3.4 cm) were independently reviewed by three radiologists. Inter-rater agreement was determined by prevalence/bias-adjusted kappa. Hepatic fat signal fraction (FS%) was independently calculated. HCC features were compared by FS% at MRI using logistic regression analysis and histologic steatosis grade using Cochran-Armitage test for trend, stratified by cirrhotic liver morphology or histologic fibrosis stage. Receiver operating characteristic curves were generated to determine the sensitivity and specificity for major HCC features by FS%. Major HCC features included arterial phase hyperenhancement (APHE) in 45 (93%), portal venous phase washout (PVWO) in 30 (63%), delayed phase washout (DPWO) in 38 (79%) and enhancing "capsule" in 34 (71%). Cirrhotic morphology was present in 22 (46%). Inter-rater agreement was 0.75 for APHE, 0.42–0.58 for PVWO, 0.58–0.71 for DPWO and 0.38–0.67 for enhancing "capsule". There was an 18%, 14% and 22% increase in the odds of absent PVWO, DPWO and capsule appearance for every 1% increase in hepatic FS% in patients with non-cirrhotic liver morphology (p = 0.011, 0.040 and 0.029, respectively). Hepatic FS% ≥ 14.8% had a sensitivity and specificity of 64 and 100% for absent PVWO and 71 and 90% for absent DPWO in patients with non-cirrhotic liver morphology. Absent washout and capsule appearance are associated with increasing hepatic steatosis in patients with non-cirrhotic, NAFLD-associated HCC. In patients with non-cirrhotic, non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC), absent HCC washout and capsule appearance are associated with increasing hepatic steatosis, thereby potentially impacting the noninvasive imaging diagnosis of HCC in these patients. Lack of washout or capsule appearance in steatotic livers at MRI may require alternative criteria for the diagnosis of HCC in patients with non-cirrhotic NAFLD. [ABSTRACT FROM AUTHOR]