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Background Two-drug antiretroviral therapy (ART), including long-acting injectable cabotegravir and rilpivirine (LAI CAB/RPV), is increasingly used for treatment of people with HIV. Many two-drug regimens do not contain tenofovir (TFV), and guidelines recommend ensuring patients are not chronically infected with hepatitis B virus (HBV) before switching to a TFV-free regimen since this could lead to HBV reactivation. The approach to regimen switching in patients who are HBV surface antigen (sAg) negative but who are HBV core antibody (HBcAb) positive is less clear. We describe three cases of HBV low-level viremia in patients switched to LAI CAB/RPV and who were HBcAb positive and sAg negative. Methods We conducted a retrospective case series of patients with HIV switching to LAI CAB/RPV who were HBcAb positive and sAg negative. We reviewed pre-switch HBV studies, history of HBV vaccination, current ART, CD4 cell count, and HIV viral load, and liver function tests (LFTs) where available. After switching to LAI CAB/RPV, we reviewed patients’ HBV DNA PCR, HBVsAg, and ART management. Results Of the 149 patients in our clinic who were switched to LAI CAB/RPV, 38 (25.5%) were HBcAb positive and sAg negative. Of these 38 patients, three (7.9%) developed HBV viremia (Figure 1). Two of the patients were switched back to a TFV-containing three-drug regimen with subsequent suppression of HBV DNA levels. Through shared decision-making, the third patient opted to continue LAI CAB/RBV. Repeat HBV DNA levels were detected but remained low and the patient’s sAg remained negative. All patients’ LFTs remained within normal limits. Of interest, one of the three patients had a surface antibody level of 115 mIU/mL at baseline. Conclusion Our case series describes three cases of HBV low-level viremia following a switch off of HBV-active ART to LAI CAB/RPV. The clinical significance of this low-level viremia is unclear and warrants further investigation. We recommend a post-hoc analysis of stored samples from patients in ATLAS, FLAIR, and ATLAS-2M who were HBcAb positive to determine if low-level HBV viremia occurred in these patients and if surface antibody levels influenced the likelihood of reactivation. Disclosures Lucas Hill, PharmD, AAHIVP, Gilead Sciences: Speakers Bureau.

PurposeInformation is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment.MethodsNewly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test.ResultsOf 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy.ConclusionMany patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.

BackgroundPersons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US).MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals.ResultsWe identified 24 studies published between 1996–2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach).ConclusionsA very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in all other regions. Between 2010 and 2019, non-alcoholic steatohepatitis (NASH) and alcohol had the fastest growing ASDRs, while HCV and HBV declined. Urgent measures are required at a global level to tackle underlying metabolic risk factors and slow the growing burden of NASH-associated liver cancer, especially in the Americas.

Background There is a four-fold risk for hepatitis B infection among healthcare workers compared to the general population. Due to limited access to diagnosis and treatment of hepatitis B in many resource-constrained settings, there is a real risk that only few healthcare workers with viral hepatitis may get screened or diagnosed and treated. Studies on hepatitis B vaccination among healthcare workers in developing countries are sparse and this bodes ill for intervention and support. The aim of the study was to estimate the prevalence and explored the associated factors that predicted the uptake of the required, full dosage of hepatitis B vaccination among healthcare workers (HCWs) in five developing countries using nationally representative data. Methods We used recent datasets from the Demographic and Health Surveys Program’s Service Provision Assessment Survey. Descriptive summary statistics and logistic regressions were used to produce the results. Statistical significance was pegged at p Results The proportion of HCWs who received the required doses of hepatitis B vaccine in Afghanistan, Haiti, Malawi, Nepal, and Senegal were 69.1%, 11.3%, 15.4%, 46.5%, and 17.6%, respectively. Gender, occupational qualification, and years of education were significant correlates of receiving the required doses of hepatitis B among HCWs. Conclusions Given the increased risk of hepatitis B infection among healthcare workers, policymakers in developing countries should intensify education campaigns among HCWs and, perhaps, must take it a step further by making hepatitis B vaccination compulsory and a key requirement for employment, especially among those workers who regularly encounter bodily fluids of patients.

Objective Immunosuppressant drugs can increase the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) and tuberculosis (TB) reactivation. Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry, we examined pre-treatment screening among new users of biologic or targeted synthetic disease modifying drugs (DMARDs). Methods Data, derived from RISE, included patients ≥ 18 years old who were new users of biologic or targeted synthetic DMARDs. We developed quality measures related to pre-treatment screening for HBV, HCV, and TB in addition to a “composite” measure for all applicable tests. We assessed patient-level screening rates, practice-level variation among practices reporting on ≥ 20 patients, and the frequency of positive results. Results We included 26,802 patients across 213 rheumatology practices nationwide. Patients were 58 (14) years old, 75.9% female; 59.6% had rheumatoid arthritis, and TNFi were the most common index DMARDs (64.9%). Overall, 44.8% and 40.5% patients had any documented HBV or HCV screening, respectively, prior to the index date; 29.7% had TB screening in the year prior to drug start. Only 15.5% had documentation of screening for all appropriate infections prior to drug start. Practice-level performance on the composite measure was low (range 0 to 48.3%). 2.4% of screening tests were positive. Conclusion We found gaps in documentation of key safety measures among practices participating in RISE. Given the small but significant number of patients with active or latent infections that pose safety risks, developing standardized and reliable strategies to capture safety screening measures is paramount.

BACKGROUND: There is limited information on perinatal outcomes in HIV-hepatitis B virus (HBV) coinfection. METHODS: HIV Prevention Trials Network (HPTN) 046 was a randomized double-blind placebo-controlled trial of perinatal transmission that evaluated 6 months of infant nevirapine versus placebo among breast-fed infants. Women living with HIV and their infants enrolled in sub-Saharan Africa from 2007 to 2010; 78% received antiretroviral therapy (ART). Maternal samples were tested for hepatitis B surface antigen (HBsAg). High and low HBV viral load (VL) was defined as ≥10 IU/mL and

Background Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use. Methods We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV. Results We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%). Conclusion The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

BackgroundThere are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV.MethodsThe PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly.ResultsOf 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ).ConclusionWith HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.

Objective: There is a lack of controlled studies of community-wide interventions to increase screening for hepatitis B (HBV) among Asian Americans, particularly Vietnamese Americans, who disproportionately suffer from HBV-related illnesses. The objective of our study was to develop, implement, and evaluate the effectiveness of a media campaign to promote HBV screening among Vietnamese Americans. Design: We designed and implemented a three-year media campaign promoting HBV screening among Vietnamese Americans. Evaluation consisted of cross-sectional pre- and post-intervention population-based telephone surveys of Vietnamese Americans adults age 18-64 who spoke English or Vietnamese and lived in the Northern California (intervention) or Greater Washington, D.C. (comparison) communities in 2007 or 2011. Statistical analysis was completed in 2012. The main outcome was self-report of HBV testing, defined as participants answering 'Yes' to the question: 'Have you ever had a blood test to check for hepatitis B?' Results: The sample sizes at pre- and post-intervention were 1,704 and 1,666, respectively. Both communities reported increased exposure to HBV-related booklets, radio and television advertisements, and websites. Only the intervention community reported increased exposure to newspaper elements. HBV screening increased in both communities (intervention: 65.3% to 73.1%, p

Objectives New specialty drugs such as biologics are now available in record numbers, presenting increased safety risks for people with immune-mediated diseases. However, comprehensive assessments of patient safety for these drugs are lacking. We examined performance on key patient safety measures, such as screening for latent tuberculosis (LTBI), hepatitis B virus (HBV), and hepatitis C virus (HCV), for new users of a broad group of specialty medications. Methods Data were extracted via electronic health record data warehouses of a large university health system using structured queries, and extensive chart review was performed to confirm measure elements. We included all new users of immunosuppressive specialty drugs between 2013 and 2017. We assessed screening for LTBI, HBV, and HCV from 12 months before through 60 days after medication initiation, and calculated performance on a composite measure that required screening for all three infections. Multivariable logistic regression was used to assess differences in screening across specialties, adjusting for patient race, sex, age, and comorbidities. Results Among 2027 patients, the most common drugs prescribed were adalimumab (32%), etanercept (24%), infliximab (19%), and ustekinumab (9%). Overall, 62% of patients were screened for LTBI, 42% for HBV, and 33% for HCV. Only 26% of patients were screened appropriately for all three infections. Screening patterns differed significantly according to treating specialty. Conclusions We found gaps in ambulatory safety for patients treated with immunosuppressive specialty drugs for diverse inflammatory conditions across all relevant treating specialties. More robust safety protocols are urgently needed to prevent serious patient safety events in this high-risk population.

Background Racial/ethnic minorities bear a disproportionate burden of hepatitis B virus (HBV) infection and disease. Disparities in HBV screening contribute to worse outcomes for communities of color. We examined the impact of race/ethnicity, language preference, and having a usual place of care on HBV screening in a multilingual, urban cohort. Methods We used questions from the Health Information National Trends Survey and added validated questions about healthcare access and health literacy. We administered this survey in English, Spanish, and Chinese to a selected convenience sample of San Francisco city/county residents in 2017, with pre-specified targets for populations with known cancer disparities: 25% Spanish-speaking, 25% Chinese-speaking, and 25% Black Americans. Using weighted multivariable logistic regression analyses, we assessed how race/ethnicity, language preference, and having a usual place of care impacts self-report of HBV screening. Results Overall, 1027 participants completed the survey (50% of surveys administered in English, 25% in Spanish, and 25% in Chinese). Only 50% of participants reported HBV screening. In multivariable analysis, Black (OR = 0.20, 95% CI 0.08–0.49), Latinx (OR = 0.33, 95% CI 0.13–0.85), Asian (OR = 0.31, 95% CI 0.10, 0.94), and ‘Other’ race/ethnicity (OR = 0.17, 95% CI 0.05–0.53) respondents had lower odds of HBV screening compared to non-Hispanic White respondents. Participants who had insurance had increased odds of HBV screening (OR = 2.70, 95% CI 1.48–4.93). Conclusions HBV screening disparities persist for Black Americans, Asian Americans, Latinx, and the uninsured. Future studies should explore reasons why current strategies have not been implemented or are not successful, particularly in addressing racial/ethnic and insurance disparities.

This survey study evaluates how clinicians approach hepatitis B virus (HBV) vaccination and monitoring in patients with HIV. Providers have clinical practices that vary greatly from one another and from current guidelines, especially for patients who do not seroconvert after initial HBV vaccination and for patients with isolated hepatitis B core antibody.

A quality improvement collaborative evaluated Hepatitis B virus (HBV) care for resettled refugees and identified strategies to enhance care. 682 of the 12,934 refugees from five refugee health clinics in Colorado, Minnesota, and Pennsylvania had chronic HBV. Timely care was defined relative to a HBsAg + result: staging (HBV DNA, hepatitis Be antigen, hepatitis Be antibody, alanine transaminase testing) within 14days, comorbid infection screening (hepatitis C virus and HIV) within 14days, and linkage to care (HBV specialist referral within 30days and visit within 6months). Completed labs included: HBV DNA (93%), hepatitis Be antigen (94%), hepatitis Be antibody (92%), alanine transaminase (92%), hepatitis C screening (86%), HIV screening (97%). 20% had HBV specialist referrals within 30days; 36% were seen within 6months. Standardized reflex HBV testing and specialist referral should be prioritized at the initial screening due to the association with timely care.

N6-methyladenosine (m6A) is the most prevalent modification of mammalian cellular RNAs. m6A methylation is linked to epigenetic regulation of several aspects of gene expression, including RNA stability, splicing, nuclear export, RNA folding, and translational activity. m6A modification is reversibly catalyzed by methyltransferases (m6A writers) and demethylases (m6A erasers), and the dynamics of m6A-modified RNA are regulated by m6A-binding proteins (m6A readers). Recently, several studies have shown that m6A methylation sites have been identified in hepatitis B virus (HBV) transcripts and the hepatitis C virus (HCV) RNA genome. Here, we review the role of m6A modification in HBV/HCV replication and its contribution to liver disease pathogenesis. A better understanding of the functions of m6A methylation in the life cycles of HBV and HCV is required to establish the role of these modifications in liver diseases associated with these viral infections., Hepatitis: Role of RNA modification Further investigations into the role of RNA modifications during hepatitis B and C infections could improve understanding of the hepatitis-associated liver disease. The most common RNA modification found in mammalian cells is N6-methyladenosine (m6A), which is linked to multiple cellular processes including gene regulation. This modification has also been identified in viral RNA, prompting Geon-Woo Kim and Aleem Siddiqui at the University of California, San Diego, USA, to review understanding of m6A modification during hepatitis virus infections. Depending on which part of the viral RNA is m6A-methylated, m6A modification induces complex changes in the viral life cycle. Infection with either hepatitis B or C virus also affects m6A modifications in host cellular RNA, influencing gene expression and inhibiting immunity. This may influence the development of liver disease and cancer during chronic hepatitis infection.

BACKGROUND: A greater understanding of the determinants of health behavior among those with and at-risk for 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 multi-faceted 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

Background and aims Epitranscriptomic modification of RNA has emerged as the most prevalent form of regulation of gene expression that affects development, differentiation, metabolism, viral infections, and most notably cancer. We have previously shown that hepatitis B virus (HBV) transcripts are modified by N6 methyladenosine (m6 A) addition. HBV also affects m6 A modification of several host RNAs, including phosphatase and tensin homolog (PTEN), a well-known tumor suppressor. PTEN plays a critical role in antiviral innate immunity and the development of hepatocellular carcinoma (HCC). Reports have shown that PTEN controlled interferon regulatory factor 3 (IRF-3) nuclear localization by negative phosphorylation of IRF-3 at Ser97, and PTEN reduced carcinogenesis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/AKT pathway. Approach and results Here, we show that HBV significantly increases the m6 A modification of PTEN RNA, which contributes to its instability with a corresponding decrease in PTEN protein levels. This is reversed in cells in which the expression of m6 A methyltransferases is silenced. PTEN expression directly increases activated IRF-3 nuclear import and subsequent interferon synthesis. In the absence of PTEN, IRF-3 dephosphorylation at the Ser97 site is decreased and interferon synthesis is crippled. In chronic HBV patient biopsy samples, m6 A-modified PTEN mRNA levels were uniformly up-regulated with a concomitant decrease of PTEN mRNA levels. HBV gene expression also activated the PI3K/AKT pathway by regulating PTEN mRNA stability in HCC cell lines. Conclusions The m6 A epitranscriptomic regulation of PTEN by HBV affects innate immunity by inhibiting IRF-3 nuclear import and the development of HCC by activating the PI3K/AKT pathway. Our studies collectively provide new insights into the mechanisms of HBV-directed immune evasion and HBV-associated hepatocarcinogenesis through m6 A modification of the host PTEN mRNAs.

Chronic hepatitis B virus (HBV) infections are one of the leading causes of cirrhosis and hepatocellular carcinoma. N6-methyladenosine (m(6)A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally. Previously, we reported the dual functional role of m(6)A modification of HBV transcripts in the viral life cycle. Here, we show that viral HBV X (HBx) protein is responsible for the m(6)A modifications of viral transcripts. HBV genomes defective in HBx failed to induce m(6)A modifications of HBV RNAs during infection/transfection, while ectopic expression of HBx restores m(6)A modifications of the viral RNAs but not the mutant HBx carrying the nuclear export signal. Using chromatin immunoprecipitation assays, we provide evidence that HBx and m(6)A methyltransferase complexes are localized on the HBV minichromosome to achieve cotranscriptional m(6)A modification of viral RNAs. HBx interacts with METTL3 and 14 to carry out methylation activity and also modestly stimulates their nuclear import. This role of HBx in mediating m(6)A modification also extends to host phosphatase and tensin homolog (PTEN) mRNA. This study provides insight into how a viral protein recruits RNA methylation machinery to m(6)A-modify RNAs.

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline - an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their "dispositional endotype" at pre-vaccination baseline, could dictate response to vaccination.

Genomic variants of the hepatitis B virus (HBV) preS/S protein are well-known to occur. Typically, immunity is gained through recovered HBV infection or by immunization. Very rarely, there are certain mutations that may enable HBV escape from the immune detection. PreS/S mutants may present with unpredictable pathobiologic, clinical, and transmittable implications. Standard laboratory testing for genomic HBV variants is not routinely performed by reference guidelines. s-variant HBV management remains challenging. Herein is a case of s-variant chronic HBV infection in a 55-year-old man. Diagnosis and treatment are described.

Nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is projected to become the leading indication for liver transplantation. Previous studies indicate that tumor growth rates (TGR) may predict survival and were helpful in determining HCC surveillance intervals. Therefore, we aimed to determine its usefulness in predicting clinical outcomes and treatments. We conducted a retrospective study of hepatitis B, C and NAFLD-HCC cases. TGR was measured using 2-consecutive pre-treatment contrast-enhanced imaging studies ≥ 25 days apart. A multivariate regression model was used to determine predictors of TGR. In addition, the Cox regression model was used to evaluate the relationship between TGR and overall survival. From 2000-2019, the study cohort comprised 38, 60, and 47 HBV, HCV, and NAFLD patients, respectively, with TGRs. NAFLD-HCC tumor size was inversely correlated to the extent of liver disease as measured by Child-Pugh score (7.2 cm in non-cirrhosis; 3.7 cm, 2.6 cm, and 2.1 cm in Child A, B, and C, respectively; P < 0.001). After adjusting for baseline characteristics, the TGR per month was fastest in HBV (9.4%, 95%CI: 6.3%-12.5%) compared to HCV (4.9%, 95%CI: 2.8%-7%) and NAFLD patients (3.6%, 95%CI: 1.6%-6.7%). Predictors of TGR included elevated AFP, low albumin, and smaller tumor size. Fast TGR in viral etiologies had higher mortality [adj. hazard ratio (HR) = 2.6, 95%CI: 1.2-5.7, P = 0.02] than slow TGRs, independent of treatments. Fast TGR in NAFLD had a trend towards higher mortality (HR = 3.6, 95%CI: 0.95-13.3, P = 0.059). NAFLD-HCC patients have more indolent growths than viral-related HCC TGRs. The addition of TGR as a biomarker may assist in stratifying treatment options.

ImportanceAn estimated 862 000 persons in the US are living with chronic infection with hepatitis B virus (HBV). Persons born in regions with a prevalence of HBV infection of 2% or greater, such as countries in Africa and Asia, the Pacific Islands, and parts of South America, often become infected at birth and account for up to 95% of newly reported chronic infections in the US. Other high-prevalence populations include persons who inject drugs; men who have sex with men; persons with HIV infection; and sex partners, needle-sharing contacts, and household contacts of persons with chronic HBV infection. Up to 60% of HBV-infected persons are unaware of their infection, and many remain asymptomatic until onset of cirrhosis or end-stage liver disease.ObjectiveTo update its 2014 recommendation, the USPSTF commissioned a review of new randomized clinical trials and cohort studies published from 2014 to August 2019 that evaluated the benefits and harms of screening and antiviral therapy for preventing intermediate outcomes or health outcomes and the association between improvements in intermediate outcomes and health outcomes. New key questions focused on the yield of alternative HBV screening strategies and the accuracy of tools to identify persons at increased risk.PopulationThis recommendation statement applies to asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened for HBV infection.Evidence assessmentThe USPSTF concludes with moderate certainty that screening for HBV infection in adolescents and adults at increased risk for infection has moderate net benefit.RecommendationThe USPSTF recommends screening for HBV infection in adolescents and adults at increased risk for infection. (B recommendation).

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

Background Compare the cost-effectiveness of 2 recombinant hepatitis B virus (HBV) vaccines in patients with inflammatory bowel disease (IBD). Methods Markov models were developed for 2 IBD cohorts: (1) 40-year-old patients prior to starting IBD treatment and (2) 40-year-old patients already receiving therapy. Cohort A received full vaccination series, cohort B had primary vaccine failure and received a vaccine booster. Two vaccines were compared: adjuvanted HEPLISAV-B and nonadjuvanted Engerix-B. Clinical probabilities of acute hepatitis, chronic hepatitis, cirrhosis, fulminant hepatic failure and death, treatment costs, and effectiveness estimates were obtained from published literature. A lifetime analysis and a US payer perspective were used. Probabilistic sensitivity analyses were performed for different hypothetical scenarios. Results Analysis of cohort A showed moderate cost-effectiveness of HEPLISAV-B ($88,114 per quality-adjusted life year). Analysis of cohort B showed increased cost-effectiveness ($35,563 per quality-adjusted life year). Changing Engerix-B to HEPLISAV-B in a hypothetical group of 100,000 patients prevented 6 and 30 cases of acute hepatitis; and 4 and 5 cases of chronic hepatitis annually for cohorts A and B, respectively. It also prevented 1 and 2 cases of cirrhosis, and 1 and 2 deaths over 20 years for each cohort. Cost-effectiveness was determined by vaccination costs, patient age, and progression rate from chronic hepatitis to cirrhosis. Conclusions HEPLISAV-B is cost-effective over Engerix-B in patients receiving immunosuppressive therapy for IBD. Benefits increase with population aging and lower costs of vaccines. We advocate measuring levels of HBV antibodies in patients with IBD and favor adjuvanted vaccines when vaccination is needed.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15–0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17–0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59–58.82) and high BMI (OR = 1.19, 95% CI 1.07–1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p

Hepatitis B virus (HBV) and hepatitis C virus (HCV) affect more than 320 million people worldwide, which is more than HIV, tuberculosis (TB) and malaria combined. Elimination of HBV and HCV will, therefore, produce substantial public health and economic benefits and, most importantly, the prevention of 1.2 million deaths per year. In 2016, member states of the World Health Assembly unanimously adopted a resolution declaring that viral hepatitis should be eliminated by 2030. Currently, few countries have elimination programmes in place and even though the tools to achieve elimination are available, the right resources, commitments and allocations are lacking. During the fifth International Viral Hepatitis Elimination Meeting (IVHEM), 7–8 December 2018, Amsterdam, the Netherlands, an expert panel of clinicians, virologists and public health specialists discussed the current status of viral hepatitis elimination programmes across multiple countries, challenges in achieving elimination and the core indicators for monitoring progress, approaches that have failed and successful elimination plans.

N6-methyladenosine (m(6)A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m(6)A on both cellular and viral transcripts and defined its role in regulating numerous biological processes, including viral infection. Here, we show that m(6)A and its associated machinery regulate the life cycle of hepatitis B virus (HBV). HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m(6)A to RNA resulted in increased HBV protein expression, but overall reduced reverse transcription of the pgRNA. We mapped the m(6)A site in the HBV RNA and found that a conserved m(6)A consensus motif situated within the epsilon stem loop structure, is the site for m(6)A modification. The epsilon stem loop is located in the 3′ terminus of all HBV mRNAs and at both the 5′ and 3′ termini of the pgRNA. Mutational analysis of the identified m(6)A site in the 5′ epsilon stem loop of pgRNA revealed that m(6)A at this site is required for efficient reverse transcription of pgRNA, while m(6)A methylation of the 3′ epsilon stem loop results in destabilization of all HBV transcripts, suggesting that m(6)A has dual regulatory function for HBV RNA. Overall, this study reveals molecular insights into how m(6)A regulates HBV gene expression and reverse transcription, leading to an increased level of understanding of the HBV life cycle.

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged

Hepatitis B reactivation associated with immune suppressive and biological therapies is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to hepatitis B virus infection. The population at risk for HBV reactivation includes those who are either currently infected with HBV or have past exposure to HBV. Since curative and eradicative therapy for HBV is not currently available, there is a large reservoir of individuals at risk for HBV reactivation in the general population. HBV reactivation with its potential consequences is particularly a concern when these people are exposed to either cancer chemotherapy, immunosuppressive or biologic therapies for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid organ or bone marrow transplantation. With the advent of newer and emerging forms of targeted biologic therapies, it has become important to understand the mechanisms whereby certain therapies are more prone to HBV reactivation. The aim of this review is to provide a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention and management of hepatitis B reactivation. In addition, we provide recommendations for future research in this area.

Author(s): Adeyemi, Olusegun Adewale; Itanyi, Ijeoma Uchenna; Ozigbu, Chamberline Ekene; Stadnick, Nicole; Tsuyuki, Kiyomi; Olayiwola, Olanrewaju; Ogidi, Amaka Grace; Eze, Chuka; Aarons, Gregory Alan; Onoka, Chima Ariel; Ezeanolue, Echezona Edozie | Abstract: IntroductionSub-Saharan Africa houses over two-thirds of the 37 million people living with human immunodeficiency virus (HIV) globally and of this, 5-20% are co-infected with Hepatitis B virus (HBV). This is double jeopardy, especially for women of reproductive age in these settings, who can transmit both viruses vertically as well as horizontally to their children. The objectives of this study were to investigate the prevalence and determinants of HBV among women of reproductive age living with HIV.MethodsThis was a cross-sectional study of HIV-infected women of reproductive age in Benue State, Nigeria. Participants were eligible for the study if they were HIV-infected women (ages 18-45 years) receiving care from any of the selected study sites. A global rapid hepatitis B surface antigen (HBsAg) antibody test strip was used to test for HBsAg in plasma. A pretested questionnaire was used to collect data on sociodemographic, clinical and lifestyle characteristics of participants. We estimated prevalence of HBV infection and used multivariable logistic regression to determine factors associated with the infection at a significance level of l0.05.ResultsA total of 6577 women were screened for HBsAg. The prevalence of HBV was 10.3% (95% CI: 9.5-10.9%). Age, parity and male partner's HIV status were found to be associated with having HBV infection. Compared to women older than 40 years, the odds of HBV infection increased significantly with increasing age until age 35 years and decreased significantly with increasing parity (versus no parity). Women with HIV-infected partners and those without a partner had higher odds of HBV infection compared to women with HIV-negative partners.ConclusionHBV is hyperendemic among HIV-infected women of reproductive age in North Central Nigeria. Specific programs targeting HBV testing, vaccination and treatment of all women of reproductive age need to be developed in this resource-limited, high-need setting.

A 2014 report evaluating accuracy of serologic testing for transfusion-transmissible viruses at African blood center laboratories found sensitivities of 92%, 87%, and 90% for detecting infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), respectively (1). Following substantial investments in national blood transfusion service (NBTS) laboratories, in 2017 investigators tested proficiency at 84 blood center laboratories (29 NBTS and 55 non-NBTS) in seven African countries. A blinded panel of 25 plasma samples was shipped to each participating laboratory for testing with their usual protocols based on rapid diagnostic tests (RDTs) (2) and third and fourth generation enzyme immunoassays (EIA-3 and EIA-4). Sensitivity and specificity were estimated using separate regression models that clustered assays by laboratory and adjusted for assay type and NBTS laboratory status. Mean specificities were ≥95% for all three viruses; however, mean sensitivities were 97% for HIV-positive, 76% for HBV-positive, and 80% for HCV-positive samples. Testing sensitivities for all viruses were high when EIA-3 assays were used (≥97%). Lower sensitivities for HBV-positive samples and HCV-positive samples were associated with assay types other than EIA-3, used primarily by non-NBTS laboratories. Proficiency for HIV testing has improved following international investments, but proficiency remains suboptimal for HBV and HCV testing. In sub-Saharan African blood centers, the quality of rapid tests used for HBV and HCV screening needs to be improved or their use discouraged in favor of EIA-3 tests.

In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to 10.8% of pet cats are viremic, is unknown. We evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of DCH using PCR and in situ hybridization (ISH). DCH was detected in 43% (6/14) of chronic hepatitis cases and 28% (8/29) of HCCs, whereas cholangitis (n = 6), biliary carcinoma (n = 18) and normal liver (n = 15) all tested negative for DCH. Furthermore, in DCH-associated cases, the histologic features of inflammation and neoplasia, and the viral distribution on ISH were strikingly similar to those seen with HBV-associated disease. Several histological features common in human HBV-associated hepatitis, including piecemeal necrosis and apoptotic bodies, were identified in DCH-positive cases of chronic hepatitis. In two cases of HCC examined, the proliferation index in regions that were ISH-positive was higher than in ISH-negative regions. The intracellular distribution of virus in both hepatitis and HCC demonstrated that viral nucleic acid is present in both nuclear and cytoplasmic forms. Collectively, these findings demonstrate a compelling association between DCH and some cases of chronic hepatitis and hepatocellular carcinoma in the cat that mirrors features of HBV-associated hepatopathies. Future investigations of viral epidemiology and natural history are needed to establish the impact of DCH on feline health.

Purpose: Molecular profiling has been used to select patients for targeted therapy and determine prognosis. Noninvasive strategies are critical to hepatocellular carcinoma (HCC) given the challenge of obtaining liver tissue biopsies. Experimental Design: We analyzed blood samples from 206 patients with HCC using comprehensive genomic testing (Guardant Health) of circulating tumor DNA (ctDNA). Results: A total of 153/206 (74.3%) were men; median age, 62 years (range, 18–91 years). A total of 181/206 patients had ≥1 alteration. The total number of alterations was 680 (nonunique); median number of alterations/patient was three (range, 1–13); median mutant allele frequency (% cfDNA), 0.49% (range, 0.06%–55.03%). TP53 was the common altered gene [>120 alterations (non-unique)] followed by EGFR, MET, ARID1A, MYC, NF1, BRAF, and ERBB2 [20–38 alterations (nonunique)/gene]. Of the patients with alterations, 56.9% (103/181) had ≥1 actionable alterations, most commonly in MYC, EGFR, ERBB2, BRAF, CCNE1, MET, PIK3CA, ARID1A, CDK6, and KRAS. In these genes, amplifications occurred more frequently than mutations. Hepatitis B (HBV)-positive patients were more likely to have ERBB2 alterations, 35.7% (5/14) versus 8.8% HBV-negative (P = 0.04). Conclusions: This study represents the first large-scale analysis of blood-derived ctDNA in HCC in United States. The genomic distinction based on HCC risk factors and the high percentage of potentially actionable genomic alterations suggests potential clinical utility for this technology.

Background & aims The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. Methods We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. Results Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). Conclusions Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.

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 thoseup to 10years of age to only 12% among those older than 50years. 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>10-30years old vs Whites or Blacks who were >10 to 30years 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.

SUMMARY To understand the molecular mechanisms that mediate the anti-hepatitis B virus (HBV) effect of interferon (IFN) therapy, we conduct high-throughput bimolecular fluorescence complementation screening to identify potential physical interactions between the HBx protein and 145 IFN-stimulated genes (ISGs). Seven HBx-interacting ISGs have consistent and significant inhibitory effects on HBV replication, among which TRIM5γ suppresses HBV replication by promoting K48-linked ubiquitination and degradation of the HBx protein on the K95 ubiquitin site. The B-Box domain of TRIM5γ under overexpression conditions is sufficient to trigger HBx degradation and is responsible both for interacting with HBx and recruiting TRIM31, which is an ubiquitin ligase that triggers HBx ubiquitination. High expression levels of TRIM5γ in IFN-α-treated HBV patients might indicate a better therapeutic effect. Thus, our studies identify a crucial role for TRIM5γ and TRIM31 in promoting HBx degradation, which may facilitate the development of therapeutic agents for the treatment of patients with IFN-resistant HBV infection., Graphical Abstract, In Brief In brief, Tan et al. find that IFN-induced TRIM5γ recruits TRIM31 to degrade HBx, resulting in suppression of hepatitis B virus replication.

Hepatitis A and B co-infection among people living with HIV are public health challenges that account for an increasing degree of morbidity and mortality. Understanding the changing epidemiology, clinical manifestations, and new approaches to treatment and prevention continues to be important in the care of people living with HIV. We conducted a review of the literature that included studies on hepatitis A and HIV co-infection and hepatitis B and HIV co-infection, focusing on epidemiology, clinical manifestations, treatment, and prevention. Important updates include the changing epidemiology of hepatitis A outbreaks among the homeless and individuals who use substances, and novel approaches to hepatitis B vaccination and hepatitis B cure strategies.

BACKGROUND: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naive children in Lilongwe, Malawi. METHODS: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. RESULTS: CMV IgG was the most common positive result in all age groups (in 73% of children

Background Two million individuals with chronic hepatitis B (CHB) in the United States are at risk for premature death due to liver cancer and cirrhosis. CHB can be prevented by vaccination and controlled with treatment. Methods We created a lifetime Markov model to estimate the cost-effectiveness of strategies to prevent or treat CHB in 6 high-risk populations: foreign-born Asian/Pacific Islanders (API), Africa-born blacks (AbB), incarcerated, refugees, persons who inject drugs (PWID), and men who have sex with men (MSM). We studied 3 strategies: (a) screen for HBV infection and treat infected (“treatment only”), (b) screen for HBV susceptibility and vaccinate susceptible (“vaccination only”), and (c) screen for both and follow-up appropriately (“inclusive”). Outcomes were expressed in incremental cost-effectiveness ratios (ICERs), clinical outcomes, and new infections. Results Vaccination-only and treatment-only strategies had ICERs of $6000–$21 000 per quality-adjusted life-year (QALY) gained, respectively. The inclusive strategy added minimal cost with substantial clinical benefit, with the following costs per QALY gained vs no intervention: incarcerated $3203, PWID $8514, MSM $10 954, AbB $17 089, refugees $17 432, and API $18 009. Clinical complications dropped in the short/intermediate (1%–25%) and long (0.4%–16%) term. Findings were sensitive to age, discount rate, health state utility in immune or susceptible stages, progression rate to cirrhosis or inactive disease, and tenofovir cost. The probability of an inclusive program costing Conclusions An inclusive strategy to screen and treat or vaccinate is cost-effective in reducing the burden of hepatitis B virus among all 6 high-risk, high-prevalence populations.

Background & Aims Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. Methods We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. Results The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. Conclusions In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.

Summary Background Spontaneous loss of HBsAg (known as functional cure) in patients with chronic hepatitis B virus (HBV) infection significantly reduces liver-related complications. HBsAg loss has been suggested to be higher in non-endemic regions than in endemic regions in individual studies. We systematically determined a pooled annual rate of HBsAg loss in adults with untreated chronic HBV infection and examined the effect of regional endemicity. Methods In this systematic review and meta-analysis, we searched PubMed and Embase for observational cohort studies and non-treatment arms of randomised controlled trials reporting proportions of patients with chronic HBV infection that achieved spontaneous HBsAg loss, published up to Oct 1, 2018. We excluded randomised controlled trials from meta-analyses because of substantial cohort differences. Two reviewers (KZ and CC) independently extracted data from accepted full-text studies, with discrepancies discussed with a third reviewer (NT). We assessed rate of HBsAg loss, and stratified results by whether the underlying cohort arose primarily from an endemic region (defined as having prevalence of chronic HBV greater than 2%) or non-endemic region. This study is registered with PROSPERO, number CRD42018074086. Findings Of 5186 studies screened, 67 (11 randomised controlled trials, 39 prospective and 17 retrospective cohort studies) met the inclusion criteria and 56 were included in meta-analyses after exclusion of randomised controlled trials. Spontaneous HBsAg loss occurred in 3837 (7·8%) of 48 972 patients, with cumulative 352 381 person-years of follow-up. The pooled annual incidence of HBsAg loss was 1·17% (95% CI 0·94–1·41, I2=97%). Rates did not differ by endemicity: 1·19% (0·88–1·54) in endemic versus 1·29% (0·99–1·62) in non-endemic cohorts. Interpretation Globally, spontaneous HBsAg loss occurs infrequently (about 1% per year) in treatment-naive adults with chronic HBV infection. The low and homogeneous rate of HBsAg loss highlights the need for new therapeutics aimed at achieving functional cure across different patient groups and geographical regions. Funding NIH National Institute of Diabetes and Digestive and Kidney Diseases.

The study aimed to determine the prevalence of occult Hepatitis B virus (HBV) infection among HIV infected persons, and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV positive individuals were tested for HBV, occult HBV, and Hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV-positive individuals. The prevalence of HBV infection among HIV positive individuals was 32 (6.4%) and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost-effective. Since conventional HBV viral load assays are expensive in resource-limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV associated complications.

Among an estimated 850,000 to 2.2 million persons with chronic hepatitis B virus (HBV) infection in the United States, 70% are non-U.S.-born (1,2). All patients require linkage to care, and approximately 20%-40% require antiviral treatment (3). Without treatment, one in four persons chronically infected with HBV will die prematurely from liver failure, liver cirrhosis, or hepatocellular carcinoma (4). To mitigate morbidity and mortality, CDC funded a cooperative agreement to develop hepatitis B testing and linkage-to-care programs serving non-U.S.-born persons during October 2014-September 2017. This report describes each program's operational services and partnerships with primary care centers, community-based organizations, and public health departments to recruit non-U.S.-born persons for HBV testing using the hepatitis B surface antigen (HBsAg) and link those whose test results were positive to HBV-directed care (medical visit attendance with monitoring of HBV DNA and liver enzyme tests). Among 10,152 program participants, 757 (7.5%) were HBsAg-positive, indicative of chronic HBV infection; among these, 643 (85%) attended ≥1 medical visit, 587 (78%) received HBV-directed care, and 137 (18%) were prescribed antiviral treatment. Among 273 household contacts of HBsAg-positive persons, 39 (14%) had positive test results for HBsAg. Prevalence of current HBV infection was high in this non-U.S.-born population and among household and sexual contacts of HBV-infected persons. HBV testing and linkage to care can be achieved through partnerships with community organizations, health centers, and public health departments.

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to the risk of hepatitis B reactivation emergency. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.

OBJECTIVE: In order to facilitate regionally-specific liver cancer prevention and control, this study estimates the fraction of hepatocellular carcinoma cases attributable to five major liver cancer risk factors by geographic region. METHODS: Prevalence estimates of major hepatocellular carcinoma risk factors, including chronic infection with hepatitis B and hepatitis C, alcohol drinking, tobacco smoking, obesity, and diabetes were extracted for each country from the literature, along with recent incidence and risk estimate data, to calculate regionally specific population attributable fractions. RESULTS: Overall, 44% of hepatocellular carcinoma cases worldwide were attributable to chronic hepatitis B infection, with the majority of cases occurring in Asia. Hepatitis C was responsible for 21% of cases. Lifestyle risk factors such as alcohol drinking and obesity were responsible for a larger percentage of cases in North America and Western, Central, and Eastern Europe. Additionally, strong gender disparities were observed when looking at lifestyle risk factors, particularly tobacco smoking, in Asia and Africa. CONCLUSIONS: Prominent risk factors for hepatocellular carcinoma vary depending on region. Our findings provide useful data for developing regionally specific guidelines for liver cancer prevention and control worldwide.

BackgroundThe incidence of liver cancer in Hmong Americans is 5 times higher than that of non-Hispanic whites, and there is a low hepatitis B screening rate (24%) among Hmong adults compared with other Asian American populations. The purpose of this study was to examine the Hmong's perceptions on social-cultural determinants, traditional health beliefs, and health care system barriers that influenced community-based hepatitis B screening interventions.MethodsA qualitative method was used, integrating a collective case study research design. In-depth interviews were used to collect data from 20 Hmong adults from the greater Sacramento area. A pattern matching analytic technique was used to analyze the data. The main core elements of Culture Care Theory were used to capture the key themes presented by the participants.ResultsProtecting a family's reputation; fear of doctors, medical procedures, and test results; lack of trust in medical doctors and medical care services; and using Hmong herbal medicines and practicing spiritual healing were identified as social-cultural and traditional health belief barriers to obtaining HBV screening. Health care costs, perceived discrimination, lack of transportation, linguistic discordance, and poor quality of care were identified as barriers to accessing high-quality health care services and obtaining hepatitis B screening.ConclusionProviders, health policy makers, researchers, and community-based organizations will need to work together to develop intervention strategies to address the social-cultural factors, traditional health beliefs, and health care challenges that influence obtaining hepatitis B screening in the Hmong community. Cancer 2018;124:1576-82. © 2018 American Cancer Society.

BackgroundFatigue is a common symptom of liver disease but not well characterized in patients with chronic hepatitis B virus (HBV).AimsWe assessed the rate of fatigue using a validated instrument in patients with HBV and identified demographic, virologic, and clinical features associated with fatigue in a cross-sectional cohort study from the Hepatitis B Research Network.MethodsParticipants were English- and Spanish-speaking adults with chronic HBV who were not pregnant nor on treatment. Fatigue was measured using the PROMIS® Fatigue 7-item Short Form.ResultsThe sample included 948 adults: median age 42; 51 % female; 71 % Asian; 74 % college educated; 77 % employed; 41 % inactive HBV carriers; 36 % with active chronic disease; and 2 % with advanced fibrosis, defined as AST-platelet ratio index (APRI) > 1.50. Patients with chronic HBV had a mean fatigue T-score of 46.8 ± SD = 7.9, compared to a mean fatigue T-score of 50.0 ± 10 in the US general population (p < .0001). In univariate analyses, greater fatigue was associated with demographic and clinical features such as female sex, lower income, more comorbidities, higher APRI score, and poorer mental health (p < 0.05). In multivariate analysis, female sex (p < .001), poorer mental health (p < .001), APRI score (p = .005), and history of diabetes (p = .039) were the strongest independent predictors.ConclusionsThe frequency of fatigue in this large cohort of North American chronic HBV patients may be equal to or lower than that reported in the US general population. Patients with advanced fibrosis, more comorbidities, and poorer mental health report worse fatigue.

Background: In the United States, Korean immigrants experience a disproportionately high burden of chronic hepatitis B (HBV) viral infection and associated liver cancer compared with the general population. However, despite clear clinical guidelines, HBV serologic testing among Koreans remains persistently suboptimal. Methods: We conducted a cluster-randomized trial to evaluate a church-based small group intervention to improve HBV testing among Koreans in Los Angeles. Fifty-two Korean churches, stratified by size (small, medium, large) and location (Koreatown versus other), were randomized to intervention or control conditions. Intervention church participants attended a single-session small-group discussion on liver cancer and HBV testing, and control church participants attended a similar session on physical activity and nutrition. Outcome data consisted of self-reported HBV testing obtained via 6-month telephone follow-up interviews. Results: We recruited 1,123 individuals, 18 to 64 years of age, across the 52 churches. Ninety-two percent of the sample attended the assigned intervention session and 86% completed the 6-month follow-up. Sample characteristics included were as follows: mean age 46 years, 65% female, 97% born in Korea, 69% completed some college, and 43% insured. In an intent-to-treat analysis, the intervention produced a statistically significant effect (OR = 4.9, P < 0.001), with 19% of intervention and 6% of control group participants reporting a HBV test. Conclusion: Our intervention was successful in achieving a large and robust effect in a population at high risk of HBV infection and sequelae. Impact: The intervention was fairly resource efficient and thus has high potential for replication in other high-risk Asian groups. Cancer Epidemiol Biomarkers Prev; 24(9); 1341–9. ©2015 AACR.

Background: Although hepatitis A virus (HAV) and hepatitis B virus (HBV) infections are vaccine-preventable diseases, few homeless parolees coming out of prisons and jails have received the hepatitis A and B vaccination series. Objectives: The study focused on completion of the HAV and HBV vaccine series among homeless men on parole. The efficacy of three levels of peer coaching (PC) and nurse-delivered interventions was compared at 12-month follow-up: (a) intensive peer coaching and nurse case management (PC-NCM); (b) intensive PC intervention condition, with minimal nurse involvement; and (c) usual care (UC) intervention condition, which included minimal PC and nurse involvement. Furthermore, we assessed predictors of vaccine completion among this targeted sample. Methods: A randomized control trial was conducted with 600 recently paroled men to assess the impact of the three intervention conditions (PC-NCM vs. PC vs. UC) on reducing drug use and recidivism; of these, 345 seronegative, vaccine-eligible subjects were included in this analysis of completion of the Twinrix HAV/HBV vaccine. Logistic regression was added to assess predictors of completion of the HAV/HBV vaccine series and chi-square analysis to compare completion rates across the three levels of intervention. Results: Vaccine completion rate for the intervention conditions were 75.4% (PC-NCM), 71.8% (PC), and 71.9% (UC; p = .78). Predictors of vaccine noncompletion included being Asian and Pacific Islander, experiencing high levels of hostility, positive social support, reporting a history of injection drug use, being released early from California prisons, and being admitted for psychiatric illness. Predictors of vaccine series completion included reporting having six or more friends, recent cocaine use, and staying in drug treatment for at least 90 days. Discussion: Findings allow greater understanding of factors affecting vaccination completion in order to design more effective programs among the high-risk population of men recently released from prison and on parole.

Reactivation of hepatitis B in the context of immunosuppressive therapy may be severe and potentially fatal. The US Food and Drug Administration has recently drawn attention to the potentially fatal risk of hepatitis B reactivation in patients receiving the anti-CD20 agents ofatumumab or rituximab. This action focuses attention on the broader issue of hepatitis B virus reactivation, which may occur with a wide variety of immunosuppressive therapies in benign or malignant disease. This article summarizes the data behind this issue. These data support the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral infection by testing for hepatitis B surface antigen and the antibody to hepatitis B core antigen in serum. Those who are found to be hepatitis B surface antigen–positive should start appropriate antiviral therapy to prevent reactivation. Additionally, even those who have recovered from hepatitis B will benefit from antiviral therapy in certain circumstances because of the risks associated with a form of hepatitis B virus reactivation referred to as “reverse seroconversion.” There remain many uncertain areas that warrant further study, and further advances will benefit from close interactions between various medical specialties, regulatory agencies, and researchers. Conclusions: There is good evidence to support routine screening of all patients for hepatitis B prior to undergoing chemotherapy or immunosuppressive treatment; use of prompt antiviral treatment appears to diminish the risk of severe or fatal reactivation of hepatitis B. (Hepatology 2015;61:703-711)