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About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non‐US‐born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B‐related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B‐related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings. [ABSTRACT FROM AUTHOR]

The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, p = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145—the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients. [ABSTRACT FROM AUTHOR]

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non‐hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post‐transplant outcomes in patients with HBV or HCV positivity receiving non‐hepatic solid‐state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006–2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post‐transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p >.05). Similarly, there was no difference in post‐transplant survival between lung transplant recipients with vs. without anti‐HCV (all p >.05). Heart transplant recipients with HCV+ had higher crude post‐transplant mortality (all p <.01). Similarly, there was higher post‐transplant mortality in kidney transplant recipients with HCV+ (1‐year: 6% vs. 3%; 5‐year: 21% vs. 13%; 10‐year: 47% vs. 31%; all p <.0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post‐kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12–1.20), p <.0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p >.05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post‐transplant outcomes in non‐hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post‐transplant mortality. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and related mortality globally. However, most of the infected individuals in the United States remain undiagnosed and untreated. There is a need to understand more completely the economic and disease burden impact of removing treatment restrictions and increasing diagnosis and treatment. The PRoGReSs model, a dynamic HBV model that tracks the infected population by year, disease stage, and gender, was used to quantify the disease and economic burden of chronic HBV infection in the United States from 2020 to 2050 based on four scenarios: a status quo (base) scenario and three treat‐all scenarios, in which screening, diagnosis, and treatment were maximized at different annual treatment price levels of $5382, $2000 and $750. Compared to the base scenario, the treat‐all scenarios would avert 71,100 acute and 11,100 chronic incident cases of HBV, and 169,000 liver‐related deaths from 2020 to 2050. At an annual treatment cost of $2000, treating all HBV infections would be highly cost‐effective, and at $750 would be cost saving and would achieve a positive return on investment before 2050. Maximizing the diagnosed and treated HBV population in the United States would avert a significant number of cases of advanced liver disease and related mortality. Such interventions can also be cost‐effective compared to the status quo strategy, and cost saving at a treatment price threshold of $750 annually, above the current lowest annual treatment cost of $362. [ABSTRACT FROM AUTHOR]

Background Early, sustained hepatitis B virus (HBV) DNA suppression reduces long-term risks of hepatocellular carcinoma. Chronic hepatitis B (CHB) treatment criteria are complex. Simplifying criteria will improve timely linkage to therapy. We evaluated treatment eligibility patterns among US patients with CHB and propose stepwise simplification of CHB treatment criteria. Methods Using 2016–2020 Quest Diagnostics data, we evaluated treatment eligibility among patients with CHB (2 positive HBV tests [HBV surface antigen, HBV e antigen, or HBV DNA] ≥6 months apart) using American Association for the Study of Liver Disease (AASLD), European Association for Study of the Liver (EASL), Asian Pacific Association for Study of the Liver (APASL), and Asian American Treatment Algorithm (AATA) criteria. Results Among 84 916 patients with CHB, 6.7%, 6.2%, 5.8%, and 16.4% met AASLD, EASL, APASL, and AATA criteria, respectively. Among treatment-ineligible patients with CHB, proportion with significant fibrosis (aspartate aminotransferase platelet ratio index >0.5) were 10.4%, 10.4%, 10.8%, and 7.7% based on AASLD, EASL, APASL, and AATA, respectively. In the proposed treatment simplification, the proportion of patients with CHB eligible for therapy increased from 10.3% for step 1 (HBV DNA >20 000 IU/mL, elevated alanine aminotransferase [ALT] level) to 14.1% for step 2 (HBV >2000 IU/mL, elevated ALT level), 33.5% for step 3 (HBV DNA >2000 IU/mL, any ALT level), and 87.2% for step 4 (detectable HBV DNA, any ALT level). Conclusions A large proportion of patients with CHB not meeting established treatment criteria have significant fibrosis. Simplifying criteria to treat all patients with detectable HBV DNA will reduce complexity and heterogeneity in assessing treatment eligibility, improving treatment rates and progress toward HBV elimination. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer-related mortality in the United States and is projected to be the third leading cause of cancer-related mortality in the United States by 2030. Main risk factors include alcoholic cirrhosis, chronic hepatitis B, hepatitis C, and nonalcoholic steatohepatitis (NASH). More than half of the patients have advanced-stage disease at presentation. Currently approved frontline systemic therapy options include sorafenib, lenvatinib, and atezolizumab/bevacizumab. Over the past decade, there has been a significant improvement in survival with a median overall survival of 19.2 months reported with first-line treatment with atezolizumab/bevacizumab. Based on positive results of randomized phase III HIMALAYA trial, durvalumab and tremelimumab combination could become another frontline option. Multiple frontline clinical trials with immune checkpoint inhibitor (ICI) or ICI combined with other novel agents are underway. In the frontline setting, identifying predictive biomarkers for ICI-based or tyrosine kinase (TKI)-based therapy is an unmet need. Subsequent treatment is poorly defined in patients with prior ICI-based therapy since all the available second-line and beyond therapy was studied after first-line sorafenib. Frontline systemic therapy is poorly defined in certain subgroups of HCC such as Child–Pugh B and post-transplant recurrent HCC. The landscape of frontline HCC treatment is rapidly changing, and this article reviews the most recent treatment approaches to frontline therapy for advanced HCC. [ABSTRACT FROM AUTHOR]

Summary: Background: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the first‐line treatment agents for chronic hepatitis B virus (HBV). Recently, whether the degree to which the risk of hepatocellular carcinoma (HCC) may be reduced by ETV vs TDF has been debated. We compared the incidence of HCC among treatment‐naïve patients receiving TDF vs ETV in the United States. Methods: From a large administrative medical claims database of commercially insured patients, we identified 166,933 adults with a diagnosis of chronic hepatitis B and a minimum of 12 months of prior enrolment, of whom 3934 and 6127 initiated ETV and TDF respectively. Fine‐Gray hazard regression models incorporating treatment propensity scores (PS) were used to estimate the risk of HCC incidence associated with TDF vs ETV; variables considered for adjustment included demographic characteristics, concomitant medication use and baseline comorbidities, as well as competing events including liver transplantation and medication changes. Results: After PS weighting, the TDF and ETV groups were well‐matched. During the follow‐up, 90 patients developed HCC, including 50 receiving ETV and 40 receiving TDF, giving rise to crude incidence rates of 0.62 per 100 person‐years (PY) and 0.30 per 100 PY respectively. In PS‐weighted, multivariable analysis, TDF was associated with a subdistribution hazard ratio for HCC of 0.58 (95% confidence interval [CI]: 0.38–0.89) compared to ETV. Results were similar when patients ≥40 years and men and women were analysed separately. Conclusion: Among commercially insured, treatment‐naïve patients with chronic hepatitis B in the United States, treatment with TDF was associated with significantly lower risk of HCC than ETV. [ABSTRACT FROM AUTHOR]

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow‐up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one‐third of patients with 'definite' indications for antiviral therapy remained untreated. [ABSTRACT FROM AUTHOR]

Background An estimated 862 000 to 2.4 million people have chronic hepatitis B infection (CHB). Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk. However, diagnosis rates remain low, with only 33% of people with CHB aware of their infection. This study aimed to assess the cost-effectiveness of universal adult screening for CHB. Methods We used a Markov model to calculate the costs, population health impact, and cost-effectiveness of 1-time universal screening and CHB monitoring and treatment compared with current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-saving or cost-effectiveness based on a willingness to pay of $50 000/quality-adjusted life-year. The analysis assumed testing would be performed during routine healthcare visits and that generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates. Results At an estimated 0.24% prevalence of undiagnosed CHB, universal hepatitis B surface antigen (HBsAg) screening in adults aged 18–69 years is cost-saving compared with current practice if antiviral treatment drug costs remain below $894/year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 hepatitis B virus–related deaths at a saving of $263 000/100 000 adults screened. Conclusions Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared with current CHB screening recommendations. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) and chronic hepatitis B virus (CHB) infection can be prevented with treatment and vaccination, respectively. We reviewed epidemiology and guidelines for TB and CHB to inform strategies for reducing United States (U.S.) burden of both infections. Non-U.S.-born, compared to U.S.-born, persons have a 15-, 6-, and 8-fold higher TB incidence and latent TB infection (LTBI) and CHB prevalence, respectively; all infections disproportionately impact non-U.S.-born Asians. TB and CHB each are associated with ~ 10% mortality that results in 7- and 14-years per life lost, respectively. LTBI and CHB have significant gaps in their care cascade as 40% of LTBI and 20% of CHB patients are diagnosed, and 20% of LTBI and CHB diagnosed patients receive treatment. Reducing TB and CHB burden will require healthcare provider-, system-, and policy-level interventions, and increased funding and collaboration between public health departments and healthcare systems. Institutional Review Board Statement: Since this review article did not include primary data on patients and only focused on reviewing published data, approval by an institutional review board was not needed. [ABSTRACT FROM AUTHOR]

While hepatitis E virus (HEV) infection can increase the risk of liver decompensation and death in patients with underlying chronic liver disease (CLD), prevalence of HEV in this cohort is not well reported. Using data from the 2011–2018 National Health and Nutrition Examination Survey, we aim to evaluate seroprevalence of HEV IgG among adults with non‐alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV). HEV IgG seroprevalence between groups was evaluated with chi‐square testing, and adjusted multivariate logistic regression models evaluated for predictors of seropositivity for HEV IgG. Seroprevalence of HEV IgG was 6.58% in ALD, 8.66% in HCV, 8.81% in NAFLD and 19.86% in HBV. We observed increasing HEV IgG seroprevalence over time in our study period, and in 2015–2018, seroprevalence was highest among the individuals with HCV (10.00%) and HBV (30.30%). Older age and being born outside of the United States were associated with seropositivity for HEV IgG in ALD, NAFLD, HBV, and for HCV, older age and being at or below poverty level were associated with seroprevalence for HEV IgG. In conclusion, we observed a relatively high prevalence of HEV among adults with CLD. These data highlight the need for greater awareness and education about the role of HEV in patients with underlying CLD, improving HEV test diagnostics, and revisiting the discussion about the potential role of HEV vaccines in CLD patients who are at higher risk of decompensation and death from acute HEV infection. [ABSTRACT FROM AUTHOR]

Those living with chronic hepatitis B virus (HBV) require years, if not decades, of regular monitoring to prevent liver complications from occurring. An estimated 292 million people were living with chronic HBV globally in 2018 with approximately 2.4 million of those residing within the United States (US). This study is one of the first of its kind that aims to explore the treatment preferences for those living with chronic HBV through qualitative interviews. Participant data were collected by in‐depth telephone interviews using a semi‐structured discussion guide. A codebook guided the organization of data, and codes were developed by review of the literature (a priori) and through line‐by‐line reading of a subsample of queries. All data transcripts (N = 19) were independently double coded. Overarching themes identified from the data specific to the treatment modalities and implications of a functional HBV cure included the concern about side effects, treatment modality, frequency, duration, cost‐effectiveness and overall impact on their lives. Qualitative data analysis revealed the significant impact that an HBV functional cure would have on quality of life. Benefits of a cure were described as not having a finite course of treatment, improving overall vitality, and reducing the fear and anxiety associated with lifelong infection and potential development of liver cancer. Many individuals expressed the desire for a cure for HBV, stating it would be life‐changing, and a 'miracle'. As new therapies are in development, more research should examine in detail the treatment preferences of those living with HBV. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) infection causes most liver-related morbidity and mortality worldwide. Numerous Chinese-Americans remain unscreened, and many HBV infected individuals are not accessing adequate care. We evaluated the prevalence of chronic HBV infection, patient awareness of infection, and linkage-to-care among Chinese-Americans in northern New Jersey. Screening 898 Chinese Americans revealed 5.5% hepatitis B virus (HBV) infected, 62.7% immune, and 31.8% non-immune. Our study suggests that HBV prevalence among Chinese-American adults may be lower than previously thought, but a large percentage of the population is still at risk for infection. Thirty-one of 49 hepatitis B surface antigen (HBsAg) seropositive subjects knew of their infections, but only 5 had accessed care. Within 6–20 months after screening education, 25 participants were accessing care. These results demonstrate a need to address possibly inadequate education and other important barriers preventing linkage to care (LTC). [ABSTRACT FROM AUTHOR]

INTRODUCTION: Previous studies, mostly small and single center, have shown gaps in the evaluation and monitoring of patients with chronic hepatitis B (CHB) virus infection. We aimed to examine the rates and predictors of adherence to guidelines for CHB care in a large nationwide cohort. METHODS: Weidentified adult patients withCHBinfection from the Truven MarketScan databases of commercially insured and Medicare patients with private insurance supplement (2007-2014) using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The initial evaluation cohort had at least 6 months follow-up, whereas at least 12 months was required for the long-term monitoring cohort. RESULTS: We analyzed 55,317 eligible patients with CHB infection: mean age 46 6 12 years, 58% men, and 14.8% with cirrhosis. Over a mean follow-up of 3.262.3 years, 55.8% had specialist (gastroenterology or infectious diseases) visits. For initial evaluation, 59% of patients received both alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA tests, whereas only 33% had ALT, HBV DNA, and hepatitis B e antigen tests, with higher frequencies among patients with specialist visits. For longterm monitoring, only 25% had both ALT and HBV DNA tests performed annually. Among patients at higher risk of developing hepatocellular carcinoma (patients with cirrhosis, male patients without cirrhosis older than 40 years, and female patients without cirrhosis older than 50), less than 40% underwent annual hepatocellular carcinoma surveillance, with25%never receiving surveillance during the study period. Predictors of optimal initial evaluation and long-term monitoring were compensated cirrhosis (odds ratio: 1.60 and 1.47, respectively) and specialist visits (odds ratio: 1.86 and 1.31, respectively) (both P < 0.001). DISCUSSION: In this large cohort of patients with CHB infection with private insurance or Medicare with private insurance supplement, we observed poor adherence to the recommended initial evaluation and longterm monitoring. Among the predictors of adherence were specialist visits. Further efforts are needed to identify barriers and improve access to care. [ABSTRACT FROM AUTHOR]

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months. [ABSTRACT FROM AUTHOR]

• HEPLISAV-B is a 2-dose Hepatitis B virus vaccine recently available in the US. • HEPLISAV-B offers earlier and higher levels of seroprotection than 3-dose Engerix-B. • HEPLISAV-B was cost-effective vs Engerix-B for multiple high-risk adult populations. • HEPLISAV-B was cost-effective for universal vaccination of adults. The hepatitis B virus is highly infectious and can cause incurable liver disease, leading to high morbidity rates, increased healthcare utilization, and high mortality. Multiple preventative hepatitis B vaccine options have been available for decades, but adherence to the traditional 6-month vaccine schedule for the approved 3-dose series remains low in adult populations at risk of hepatitis B exposure. A 2-dose hepatitis B vaccine (HEPLISAV-B) approved by the US Food and Drug Administration in 2017 induces rapid seroprotection within 1 month and has a safety profile comparable to a commonly used 3-dose vaccine. In a previous cost-effectiveness study, HEPLISAV-B had a favorable cost-effectiveness profile for multiple at-risk populations. The goal of the current analysis was to update and extend previous findings by evaluating cost-effectiveness of HEPLISAV-B compared with a 3-dose vaccine (Engerix-B) in selected adult populations, including patients with diabetes, chronic liver or kidney disease, end-stage renal disease, healthcare personnel, travelers to countries with endemic hepatitis B, and a public health population. Cost-effectiveness was measured as incremental cost-effectiveness ratios using a health economics Markov model that accounts for adherence rates, seroprotection rates, healthcare costs, and current pricing considerations. Patients progressed between a series of health states, and the difference in lifetime spending and survival for individuals receiving either HEPLISAV-B or Engerix-B was estimated from the perspective of a US managed care payer, HEPLISAV-B had favorable cost-effectiveness profiles for patients with diabetes, healthcare personnel, travelers, and patients with chronic liver disease and dominant incremental cost-effectiveness ratios for patients with chronic kidney disease and end-stage renal disease. A probabilistic sensitivity analysis supported the robustness of the cost-effectiveness profiles, and an additional analysis indicated that HEPLISAV-B was cost-effective in the general adult population. Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) is a major global health issue disproportionately affecting Asian Americans and other immigrant populations in the United States. Despite the high risk of morbid complications from CHB, the majority of individuals with CHB do not access healthcare due to a complex of barriers. These barriers influence health literacy which may affect behaviors linked to hepatitis B care. We aimed to identify and evaluate various sociocultural factors and how they interact with health literacy to impact CHB care and health seeking in a Korean American population.Methods: A total of 28 Korean American individuals with CHB were divided into 5 different focus discussion groups. This study investigated the participants' sociocultural backgrounds as well as their awareness and utilization of the healthcare system that could influence their health literacy and behaviors in accessing care.Results: Our analysis identified and concentrated on three themes that emerged from these discussions: low risk perception and knowledge of CHB and its complications; language, immigrant status, and stigma; and financial and institutional barriers. The participants' overall awareness of the disease and prevention methods demonstrated poor understanding of important characteristics and potential outcomes of the disease. Additionally, differences in cultural expectations and a lack of understanding and utilization of healthcare systems affected health literacy in further limiting participants' motivation to seek care.Conclusions: The present study suggests that there are culture-specific barriers to health literacy governing individuals' health behavior in accessing hepatitis B care. These findings may inform strategies for developing culturally tailored resources and programs and for facilitating the implementation of community-wide hepatitis B education and screening initiatives in immigrant communities. [ABSTRACT FROM AUTHOR]

Importance: An 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.Objective: To 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.Population: This 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 Assessment: The USPSTF concludes with moderate certainty that screening for HBV infection in adolescents and adults at increased risk for infection has moderate net benefit.Recommendation: The USPSTF recommends screening for HBV infection in adolescents and adults at increased risk for infection. (B recommendation). [ABSTRACT FROM AUTHOR]

• Heplisav-B's shortened dosing schedule is advantageous for high risk populations. • Heplisav-B results in decreased HBV-related morbidity and mortality. • Heplisav-B is cost-saving vs Engerix-B in adults with diabetes, obesity, CKD, HIV; older adults, PWID. Vaccination is the primary strategy to prevent hepatitis B virus (HBV) infection in the United States. Prior to 2017, most standard hepatitis B vaccine schedules required 3 doses over 6 months. Heplisav-B, approved in 2017, is administered in 2 doses over a 1 month time period but has a higher per-dose cost ($115.75 per dose compared to $57.25 per Engerix-B dose, costs as of June 1, 2019). We aimed to assess the cost-utility of providing the two-dose Heplisav-B vaccine compared to a three-dose Engerix-B vaccine among adult populations currently recommended for vaccination against hepatitis B. We used a decision-tree model with microsimulation and a Markov disease progression process to assess the cost-utility separately for the following populations: adults with diabetes, obesity, chronic kidney disease, HIV; non-responders to previous hepatitis B vaccination; older adults; and persons who inject drugs (PWID). We modeled epidemiologic outcomes (incident HBV infections, sequelae and related deaths), costs (2019 USD) and benefits (quality-adjusted life years, QALYs) and compared them across strategies. Sensitivity analyses assessed the cost-utility at varying estimates of Heplisav-B efficacy. In the base case scenario for each population, vaccination with Heplisav-B resulted in fewer HBV infections (37.5–59.8% averted), sequelae, and HBV-related deaths (36.3–71.4% averted). Heplisav-B resulted in decreased costs and increased benefits compared to Engerix-B for all populations except non-responders. Incremental costs from the baseline strategy ranged from $4746.78 saved (PWID) to $14.15 added cost (non-responders). Incremental benefits per person ranged from 0.00005 QALYs (older adults) to 0.7 QALYs (PWID). For persons with HIV and PWID, Heplisav-B resulted in lower costs and increased benefits in all scenarios in which Heplisav-B series efficacy was at least 80%. Vaccination using Heplisav-B is a cost-saving strategy compared to Engerix-B for adults with diabetes, chronic kidney disease, obesity, and HIV; older adults; and PWID. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hepatitis B infection is an important contributor to mortality in the United States, yet impact of available and effective oral antivirals on mortality among infected individuals is unknown. Aims: To compare risks and predictors of mortality in a recent time period between those with chronic, prior and no hepatitis B infection. Methods: This is a population‐based cohort study of National Health and Nutrition Examination Surveys participants between 1999 and 2014 linked to National Death Index data. Adults aged 20 years or older with hepatitis B serologic testing were included. Outcomes of all‐cause and liver‐related mortality were evaluated using Cox regression. Results: Of 39 206 participants, 192 (0.5%) had chronic and 2694 (6.9%) had prior hepatitis B infection. The all‐cause age/sex‐standardised mortality rates for chronic, prior and uninfected were 21.4, 15.1 and 11.8 per 1000 person‐years respectively. Liver‐related mortality occurred at respective rates of 4.1, 0.3 and 0.1 per 1000 person‐years. In multivariable analyses, those with chronic infection had 1.9‐fold (95% CI 1.1‐3.3) increased hazard of all‐cause mortality and 13.3‐fold (95% CI 3.9‐45.5) increased hazard of liver‐related mortality compared to uninfected. Predictors of all‐cause mortality among chronic infection included heavy alcohol use (HR 18.3, 95% CI 3.3‐100.6) and higher alanine aminotransferase (HR 1.02, 95% CI 1.00‐1.03). Conclusions: Mortality among adults living with chronic hepatitis B infection still exceeds that of uninfected despite availability of improved therapeutics. Identification of chronic infection, initiation of treatment among eligible and modulation of co‐factors for disease progression are needed to improve survival. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about health-related quality of life (HRQoL) in patients with chronic hepatitis B virus (CHB) infection in the United States. Our goal is to understand factors associated with HRQoL in this population.Methods: We conducted a survey to assess HRQoL and behavioral risks among patients with CHB infection from four large U.S. health care systems. Primary outcomes were generated from the SF-8 scale to assess HRQoL, as measured by the mental component scores (MCS) and physical component scores (PCS). The survey also measured socio-demographic information, hepatitis-related behavioral risk factors, treatment exposure/history, stress, and social support. We supplemented survey data with electronic health records data on patient income, insurance, disease severity, and comorbidities. Multivariate analysis was used to estimate and compare adjusted least square means of MCS and PCS, and examine which risk factors were associated with lower MCS and PCS.Results: Nine hundred sixty-nine patients (44.6%) responded to the survey. Current life stressors and unemployment were associated with both lower MCS and PCS results in multivariate analyses. Lower MCS was also associated with White race and low social support, while lower PCS was also associated with Medicaid insurance.Conclusions: Stressful life events and unemployment were related to mental and physical health status of CHB patients. Those who have social support have better mental health; White and Medicaid patients are more likely to have poorer mental and physical health, respectively. Management of CHB patients should include stress management, social support, and financial or employment assistance. [ABSTRACT FROM AUTHOR]

Occult HBV infection (OBI) is defined as the presence of detectable hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative individuals. Rarely, OBI is attributed to mutant HBV that cannot be detected by commercial assays, but most cases occur in the setting of chronic hepatitis B, particularly infection with wild-type viruses associated with strong HBV suppression. OBI is a high-risk diagnosis as it is associated with multiple complications: HBV reactivation in immunocompromised states, transmission of HBV, progression of liver disease, and hepatocellular carcinoma. The diagnosis is also easy to overlook, as the negative HBsAg in such cases can be falsely reassuring. This case series describes four male patients (mean age 51) who were diagnosed with OBI in the same military treatment facility between February 2018 and October 2018. Two of the four patients were active duty service members at the time of diagnosis. These patients had variable clinical presentations and outcomes. This case series illustrates the clinical significance of OBI and the importance of screening for OBI in HBsAg negative patients with signs of chronic or severe hepatic inflammation. It also prompts an intriguing question regarding the prevalence of both HBV and OBI in the United States military and whether or not routine screening for HBV should be implemented in this population. Further study is warranted to determine if adding HBV core antibody to a universally employed screening regimen would be beneficial. [ABSTRACT FROM AUTHOR]

Background: In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear.Methods: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage (SEER-Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66 years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age-standardized incidence rates of HCV-attributable, HBV-attributable, and HCV/HBV-unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence.Results: Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV-attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV-attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV-unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV-attributable and HBV-attributable HCC were noted among individuals aged 66 to 75 years, men, and individuals of Asian ancestry.Conclusions: Among Americans aged ≥66 years, HCC rates increased rapidly between 2001 and 2013. Although HCV-attributable cases contributed substantially to this increase, rates of HBV-attributable and HCV/HBV-unrelated HCC also rose during this period. [ABSTRACT FROM AUTHOR]

Cirrhosis is a leading cause of morbidity and mortality in the United States. Early readmission to the hospital after discharge increases the clinical and economic burden of cirrhosis patients. We aim to evaluate the prevalence and predictors of early hospital readmission among cirrhosis patients among an underserved safety-net health system. All consecutive adults with cirrhosis seen at the gastroenterology clinics at our safety-net health system from 2014 to 2016 were retrospectively evaluate to determine rates of 30-day readmission after hospital discharge. Comparison of readmission rates between groups used chi-square testing. Overall predictors of 30-day hospital readmission were evaluated using multivariate logistic regression models, with variables included in the model selected a priori based on clinical significance to the outcome. Among 230 cirrhosis patients (63.5% men, 80.6% were nonwhite minorities), 27.1% had chronic hepatitis C virus; 16.0%, chronic hepatitis B virus; 34.2%, alcoholic cirrhosis; and 8.0%, nonalcoholic steatohepatitis. Overall 30-day hospital readmission rates were 31.3%. There was a trend towards higher rates of 30-day readmission in men than in women (23.9% vs. 7.4%, P = 0.075) and trend towards higher readmission in Hispanics than in non-Hispanic whites (35.3% vs. 14.3%, P = 0.093). On multivariate regression, hepatic encephalopathy was the strongest positive predictor of early 30-day hospital readmission (odds ratio 4.40, 95% confidence interval 1.25–7.28, P = 0.02). Among underserved safety-net cirrhosis patients, 30-day hospital readmission rates were over 30%. Given that presence of hepatic encephalopathy was most strongly correlated with readmissions, targeted interventions to improve management of hepatic encephalopathy may have the greatest impact on improving cirrhosis-related outcomes. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B infection (CHB) is a condition that needs ongoing care such as monitoring for liver enzymes (ALT) and HBV DNA tests in treated and untreated patients, and annual imaging evaluation for liver cancer. Although follow-up care and treatment might seem straight forward, an estimated two-thirds of those who are aware of their infection are not seeing a health care provider, and more than half of those who are eligible for treatment do not receive it. This study aimed to compile and examine studies related to the barriers of disease monitoring, treatment, and liver cancer surveillance for CHB patients in the United States (US). A total of 4439 studies on monitoring and surveillance of CHB published between 2007 and 2018 were identified through a search of electronic databases. After critical assessment, the authors included 42 studies, divided into categories: 'patient-related barriers'; 'provider-related barriers'; and 'system-related barriers'. Among the patient-related barriers, one of the most frequent factors invoked in failing to have adequate surveillance was lack of patient's knowledge. In the provider-related barrier category, a lack of disease knowledge and adherence to guidelines was frequently reported. For the system-related barrier category, the only recurrent mention was a lack of clarity in guidelines or lack of guidelines from certain national institutions. This review summarizes and highlights the need for long-term disease management improvement of chronic hepatitis B infection for patients and healthcare providers that care for them. [ABSTRACT FROM AUTHOR]

Summary: The World Health Organization has set the goal of reducing the hepatitis‐related mortality rate by 65% between 2015 and 2030. Diagnosis and awareness of infection is the first essential step towards achieving this goal. Our study examined the current awareness rate of chronic viral hepatitis in the United States and the potentially associated factors. In the National Health Nutrition and Examination Survey 2013‐2016, there were 11 488 persons who participated in serology testing for chronic viral hepatitis. We defined chronic hepatitis B virus (HBV) infection by HbsAg, HBV past exposure by anti‐HBc and hepatitis C virus (HCV) infection by HCV RNA. At risk for significant fibrosis was determined by AST to Platelet Ratio Index >0.7. Awareness of chronic HBV infection, past HBV exposure and HCV infection were present in 33.9%, 11.7% and 55.6% of participants, respectively. Among HCV‐infected baby boomers, the awareness was in 61.5%. The awareness of HBV infection was significantly higher in individuals with high education level. Age group (40‐60 years), women, non‐Black race/ethnicity and those with high household income who were born in the United States with insurance plans tend to be aware of their infection. For HCV, awareness was the lowest in Hispanics and Asians, foreign‐born who lived below the federal poverty level and low education level. Awareness among chronic viral hepatitis patients at risk for significant fibrosis was 62.0% in HBV and 38.2% in HCV infection. In conclusion, current awareness of chronic viral hepatitis in the United States remains suboptimal. Active public health policy to identify persons at risk and provide appropriate management is warranted. [ABSTRACT FROM AUTHOR]

Background According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). Methods We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. Results Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P <.001). CHB patients died at an average age of 59.8 years—14 years younger than the general U.S. population—and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851–1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81–16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. Conclusions Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB. [ABSTRACT FROM AUTHOR]

Background: Since the mid-1980s, the burden of liver cancer in the United States has doubled, with 31,411 new cases and 24,698 deaths occurring in 2014. Foreign-born individuals may be more likely to die of liver cancer than individuals in the general US-born population because of higher rates of hepatitis B infection, a low socioeconomic position, and language barriers that limit the receipt of early cancer detection and effective treatment.Methods: To determine whether liver cancer mortality rates were higher among foreign-born individuals versus US-born individuals in the United States, population-based cancer mortality data were obtained from the National Center for Health Statistics of the Centers for Disease Control and Prevention. Annual population estimates were obtained from the US Census Bureau's American Community Survey. Age-adjusted mortality rates and rate ratios (RRs) for liver cancer stratified by birth place were calculated, and the average annual percent change (AAPC) was used to evaluate trends.Results: A total of 198,557 deaths from liver and intrahepatic bile duct cancer were recorded during 2005-2014, and 16% occurred among foreign-born individuals. Overall, foreign-born individuals had a 24% higher risk of liver cancer mortality than US-born individuals (RR, 1.24; 95% confidence interval [CI], 1.22-1.25). Foreign-born individuals did not have any significant changes in liver cancer mortality rates overall, but among US-born individuals, liver cancer mortality rates significantly increased (AAPC, 2.7; 95% CI, 2.1-3.3).Conclusions: Efforts that address the major risk factors for liver cancer are needed to help to alleviate the health disparities observed among foreign-born individuals and reverse the increasing trend observed in the US-born population. [ABSTRACT FROM AUTHOR]

Background and Aims: The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices.Methods: Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated.Results: Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices.Conclusion: Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar. [ABSTRACT FROM AUTHOR]

Hepatitis B (HB) affects 240 million people around the world, and children and young adults make up a large proportion of the infected population. Approximately 1 million people die from HB each year. Despite the seriousness of HB and its complications, many are poorly linked to clinical care. A lack of health literacy may be a critical barrier hindering access to HB care for adults as well as children in these populations. We, therefore, performed a survey to assess the level of knowledge of HB among Korean American parents. The survey was conducted on 521 Korean American adults who attended community-based HB awareness campaigns held at various locations throughout the metropolitan New York area between January 2015 and November 2016. Of these, 296 parents, who had children between ages 1 and 30, were identified. All participants were asked a series of questions regarding various aspects of HB and were evaluated on the basis of their awareness on each subject. A separate questionnaire was also employed to obtain demographic characteristics of the participants. The study revealed a significant deficit of knowledge of HB in most aspects the survey evaluated. Although the majority of the participants knew that HB is a liver disease, and many of them had been screened for HB, they had a poor understanding of vaccination, screening, their own HB status, modes of HBV transmission, and the consequences and treatment of HB. The participants also had a low level of awareness of their own children’s HB status. This study demonstrates a low level of knowledge of HB among Korean American parents electing to attend a hepatitis education program. In addition, many parents are not aware of their children’s screening and immune (or non-immune) status. The lack of health literacy may contribute to poor health access in HB care, not only in adults but also in children. This suggests an urgent need for education on HB in Korean American parents as well as in young children. [ABSTRACT FROM AUTHOR]

The National Academies of Sciences, Engineering, and Medicine have concluded that eliminating the public health problem of chronic hepatitis B is feasible. We examined the economic and public health impact of reaching the World Health Organization targets of having 90 percent of chronic hepatitis B cases diagnosed and 80 percent being treated by 2030 in the United States with an annual incremental increase in screening and treatment rates. To reach the targets by 2030 would require screening approximately 14.5 million adults in at-risk populations to diagnose an estimated 870,000 undiagnosed cases and would result in substantial health gains: an increase of 16.5 million quality-adjusted life-years (QALYs), and reductions in liver-related deaths of 37 percent and in cases of compensated cirrhosis of 24 percent, decompensated liver cirrhosis of 51 percent, and liver cancer of 35 percent. Achieving the targets by 2030 would be highly cost-effective at $103 per QALY and would be cost-saving if the antiviral drug price were no more than $114 per month. Achieving them by 2025 would be cost-saving and would reduce liver-related deaths by 47 percent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B virus infection. While HDV infection in the United States is thought to be uncommon, there are limited data regarding frequency of testing, and prevalence of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using electronic medical record (EMR) data. Among 1007 HBsAg positive patients, only 121 had been tested for HDV antibody. Testing was performed primarily by gastroenterologists/hepatologists and limited testing was performed in identifiable high risk groups including those with HBV/HIV coinfection. Overall, HDV antibody was detected in 3.3% (95% C.I. = 0.9%–8.2%) An HDV RNA assay was developed and validated and 138 HBV or HBV/HIV coinfected patients were tested. The prevalence of HDV among the HBV/HIV coinfected subjects was 2.2% (95% C.I. = 0–5.3%). In a U.S. Midwestern population of HBV infected patients, HDV testing is under-employed. Overall prevalence exceeds 2% whether testing by antibody or HDV RNA and more comprehensive HDV surveillance may be indicated. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is more common in African Americans than in white Americans. We compared the epidemiologic, clinical, and virological characteristics of US-born African Americans (USAAs) to those of foreign-born African Americans (FBAAs) with chronic hepatitis B. The adult cohort study of the Hepatitis B Research Network enrolls patients with HBV infection from 21 clinical sites in the United States and Canada. A total of 237 (15%) of the adult participants with chronic HBV infection that were enrolled from January 20, 2011, to October 2, 2013, were of African descent, including 57 USAAs and 180 FBAAs (76%). Compared with FBAAs, USAAs were older and more likely to have acquired HBV through sexual exposure, to be HBeAg-positive, to have higher HBV DNA levels, and to be infected with HBV genotype A2. FBAAs from West Africa were more likely to have elevated serum alanine aminotransferase (72% vs. 50%; P < 0.01) and higher HBV DNA levels (median, 3.2 log10 IU/mL vs. 2.8 log10 IU/mL; P = 0.03) compared with East African FBAAs. The predominant HBV genotype among West African FBAAs was E (67%), whereas genotypes A (78%) and D (16%) were common in East African FBAAs. Significant differences were found between USAAs and FBAAs, highlighting the need for tailored strategies for prevention and management of chronic HBV infection for African Americans. [ABSTRACT FROM AUTHOR]

Background: Administrative databases that include diagnostic codes are valuable sources of information for research purposes.Aim: To validate diagnostic codes for hepatocellular carcinoma (HCC) in chronic hepatitis B patients.Methods: We conducted a retrospective study of patients with chronic HBV seen in the national Veterans Administration (VA). HCC cases were identified by the presence of ICD-9 code 155.0. We randomly selected 200 HBV controls without this code as controls. We manually reviewed the electronic medical record (EMR) of all cases and controls to determine HCC status. We calculated the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity for the HCC code. We conducted an implicit review of the false-positive cases to determine possible reasons for the miscoding.Results: Of the 8350 patients with HBV, 416 had an ICD-9 code for HCC. Of these 416, 332 patients had confirmed HCC and 61 did not; HCC status was indeterminate for 23 patients. Of the 200 controls, none had HCC confirmed in the EMR. The PPV ranged from 85.3 to 80.0% and specificity ranged from 99.2 to 99.0% based on classification of indeterminate cases as true versus false positives, respectively. The NPV, sensitivity, and specificity were 100%. Two-thirds of false-positive cases were diagnosed with HCC prematurely as a workup of liver mass and latter imaging and/or biopsy were not diagnostic for HCC.Conclusion: The diagnostic code of HCC in chronic HBV patients in the VHA data is predictive of the presence of HCC in medical records and can be used for epidemiological and clinical research. [ABSTRACT FROM AUTHOR]

Background: Chronic liver disease is a major cause of morbidity and mortality in the USA and China, but the etiology of liver disease, medical practice, and patient expectations in these two countries are different.Aims: To compare patient knowledge about their liver disease, patient satisfaction with liver disease care, and patient medical decision-making preference in the USA and China.Methods: Three cohorts of established adult patients with liver disease seen in liver clinics in Ann Arbor, USA, and Beijing (urban) and Hebei (rural), China, completed a survey between May and September 2014.Results: A total of 990 patients (395 USA, 398 Beijing, and 197 Hebei) were analyzed. Mean liver disease knowledge score (maximum 5) in the USA, Beijing, and Hebei patients was 4.1, 3.6, and 3.0, respectively (p < 0.001). US patients had a greater preference for collaborative decision-making: 71.8 % preferred to make treatment decisions together with the doctor, while most Chinese patients (74.6 % Beijing and 84.8 % Hebei) preferred passive decision-making. Mean satisfaction score (maximum 85) in the USA was higher than in Beijing, which in turn was higher than in Hebei (78.2 vs. 66.5 vs. 60.3, p < 0.001). There was a positive correlation between liver disease knowledge score and satisfaction score (r = 0.27, p < 0.001) and with collaborative medical decision-making (r = 0.22, p < 0.001) when responses from all sites were combined.Conclusions: Liver disease knowledge and patient satisfaction were greatest in the USA, followed by Beijing and then Hebei patients. Understanding these differences and associated factors may help to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Since 1993, how to assess the causality of serious adverse events in premarketing drug clinical trials has undergone sustained regulatory evolution in the USA. In that year, an investigational drug study for chronic hepatitis B virus infection was emergently stopped after a patient suddenly exhibited hepatic failure and lactic acidosis, which later developed, along with pancreatitis and peripheral neuropathy, in several others after drug discontinuation. Five patients eventually died, including three despite emergency liver transplantation. The drug's multisystem toxicity was not predicted by preclinical animal studies, with grave injury to human mitochondria subsequently implicated. A concerned US Food and Drug Administration (FDA) created a task force whose findings would have a lasting impact on the agency's thinking. In 1994, the FDA proposed to amend its investigational new drug reporting requirements largely based on task force recommendations for ways to enhance the likelihood that sponsors and investigators would consider investigational agents as a possible cause of serious adverse events mimicking the underlying disease or concomitant drug toxicity. Then, in its 1997 final rule for expedited safety reporting requirements for drugs and biologics, the FDA advised sponsors that such reporting of serious, unexpected clinical trial cases would be expected when "there is a reasonable suspected causal relationship between the investigational product and the adverse event (i.e., the causal relationship cannot be ruled out)." This last clause was codified into the suspected adverse drug reaction definition in the FDA's 2003 safety reporting requirements for drugs and biologics proposed rule. The negatively received suspected adverse drug reaction and proposed causality standard were not adopted in the FDA's 2010 finalized investigational new drug safety reporting regulations, the agency stating that "'reasonable possibility' means there is evidence to suggest a causal relationship between the drug and the adverse event." However, such new requirements as aggregate analysis of specific events and expedited reporting of animal or in vitro data suggesting significant harm to humans, and subsequent guidance that sponsors develop "a systematic approach" to premarketing safety assessment, are among the components of the FDA's efforts to enhance determination of a "reasonable possibility" of causality. They are also philosophically consistent with the 1993 task force recommendations, and a reminder of the inherent hazards associated with the use of investigational drugs, particularly in the early stages of human study. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful.Aims: Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality.Methods: Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012.Results: Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV.Conclusions: Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care. [ABSTRACT FROM AUTHOR]

Assiduous measures are taken to prevent perinatal transmission of hepatitis B virus ( HBV) to infants; it is unclear whether the mothers receive appropriate care for their chronic HBV. We sought to assess the quality of HBV care in hepatitis B surface antigen ( HBsAg)-positive mothers following pregnancy. HBsAg-positive women ( n = 243) who had sought prenatal care at Massachusetts General Hospital were retrospectively identified and charts reviewed. The primary outcome was adherence to the American Association for the Study of Liver Diseases ( AASLD) and American College of Obstetricians and Gynecologists guidelines. Over one-third (37%) of women were first diagnosed with HBV infection at a prenatal visit. One-third (32%) did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients. One-third (34%) of the women were at high-risk for HCC based on AASLD criteria, yet only 33% of these women underwent timely imaging. Nearly half (49%) never saw a liver specialist for their HBV care. In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist ( P = 0.001, <0.001). We demonstrate remarkably inadequate and discontinuous HBV care for chronically infected mothers following pregnancy. As HBV infection is already being identified prenatally, quality improvement measures encompassing obstetricians, primary care providers and hepatologists are needed to ensure that HBV-infected women are linked to care postpregnancy. [ABSTRACT FROM AUTHOR]

Objective. Hepatitis B virus (HBV) infection continues to be a public health threat in the United States. As many as 2.2 million people are infected, approximately 70% of whom are foreign-born, and fewer than one-third are aware of their infection. We launched an HBV testing and linkage-to-care initiative among foreign-born people. Methods. As part of the Hepatitis Testing and Linkage to Care (HepTLC) initiative, which promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites, nine U.S. programs in seven states conducted HBV screening from October 2012 to September 2014. The nine programs partnered with health-care centers and community-based organizations to recruit foreign-born people recommended for HBV testing. We assessed patient characteristics, region of origin, risk factors, hepatitis B surface antigen (HBsAg) status, and referral to medical care. Results. Of 23,144 participants tested for HBV, 1,317 (5.7%) were HBsAg positive. Of these, the median age was 47 years, 1,205 (91%) had at least one risk factor for HBV infection, 1,117 (85%) received posttest counseling, 1,098 (83%) were referred to care, and 606 (46%) attended a first medical appointment. The proportion of HBsAg-positive participants by region of origin included Africa (10%, 206/2,129), Western Pacific (6%, 616/9,673), Eastern Mediterranean (5%, 174/3,337), Southeast Asia (5%, 191/3,891), South America (2%, 6/252), Eastern Europe (2%, 6/262), and North America (1%, 17/1,936). Conclusion. Community-based HBV testing initiatives can identify substantial numbers of people with chronic HBV infection, inform them of their infection status, and provide posttest counseling and linkage to care. However, strategies are needed to improve linkage to HBV-directed medical care for foreign-born individuals living with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common symptom of liver disease but not well characterized in patients with chronic hepatitis B virus (HBV).Aims: We 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.Methods: Participants 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.Results: The 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.Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic hepatitis B (CHB) is a major cause of cirrhosis and end-stage liver disease. Not all patients with CHB require antiviral treatment but long-term monitoring is critical to identify patients who would benefit from antiviral therapy. CHB patients followed in various clinical settings may differ in disease characteristics and rates of treatment eligibility in long-term follow-up.Methods: We conducted a retrospective cohort study of 359 consecutive treatment-naive, treatment-ineligible CHB patients (228 from community GI clinics; 73 from university hepatology clinic; 58 from primary care clinic). Primary end points were the proportion of patients meeting eligibility criteria in follow-up, and the eligibility comparison among patients in various clinical settings. Univariate and multivariate Cox's proportional hazard models were used to calculate hazard ratios to identify predictors of treatment eligibility in follow-up.Results: While the majority of patients remained treatment ineligible by guideline recommendations, a sizeable proportion (23 %, 95 % CI 18-27 %) of patients subsequently met treatment eligibility in study follow-up. Reasons for meeting US Panel treatment eligibility on multivariate analysis included baseline ALT ≥ ULN (HR 1.91, p = 0.03) and baseline HBV DNA ≥ 2000 IU/mL (HR 2.6, p = 0.001). Practice setting was not a predictor.Conclusions: A significant number of patients with CHB (23 %) who were not initially treatment eligible later met treatment criteria in longer-term follow-up. Significant independent predictors of treatment eligibility included a baseline ALT ≥ ULN and elevated HBV DNA (≥2000 IU/mL for US Panel eligibility and ≥20,000 IU/mL for AASLD eligibility). This study underscores the importance of long-term follow-up for patients with CHB. [ABSTRACT FROM AUTHOR]

In the United States, improved screening of those who are at highest risk of chronic hepatitis B (CHB) has been a major focus of public health efforts, as has facilitating access to care for those with chronic infection. Despite this, data suggest that less than half of those at risk are tested, and another minority of those who harbor chronic infection receive longitudinal care for the disease. In this study by Tran et al., the authors find that even among those being treated for CHB, a vast minority receive basic testing and screening for staging and complications of CHB. [ABSTRACT FROM AUTHOR]

OVERVIEW: Over the past 15 years, the incidences of hepatitis A and B virus infection in the United States have declined significantly. By contrast, the incidence of hepatitis C virus infection, formerly stable or in decline, has increased by 75% since 2010. Suboptimal therapies of the past, insufficient provider awareness, and low screening rates have hampered efforts to improve diagnosis, management, and treatment of viral hepatitis. New screening recommendations, innovations in assessment and treatment, and an updated action plan from the U.S. Department of Health and Human Services (HHS) seem likely to lead to significant progress in the coming years. This article reviews the epidemiology, natural history, and diagnosis of viral hepatitis; discusses new screening recommendations, assessment tools, and treatments; and outlines the HHS action plan, focusing on the role of nurses in prevention and treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Chronic Hepatitis Cohort Study (CHeCS) Investigators. Infrequent clinical assessment of chronic hepatitis B patients in United States general healthcare settings" by P. R. Spradling and colleagues in the previous issue.

Abstract: Purpose: Few population-based studies have estimated the number of persons diagnosed with chronic hepatitis B (CHB) infection in the United States. Our objective was to estimate the prevalence of diagnosed CHB infection among persons enrolled in the U.S. Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania between 2000 and 2007. As part of our analyses, we confirmed the accuracy of CHB diagnoses within the Medicaid database. Methods: CHB infection was defined by the presence of two outpatients CHB diagnoses recorded more than 6 months apart. Two clinicians reviewed the medical records of a random sample of patients who met this definition to confirm the diagnosis, which enabled calculation of the positive predictive value (PPV). The period prevalence of diagnosed CHB infection among Medicaid enrollees with at least 6 months of membership from 2000 to 2007 was then estimated, adjusting for both the PPV and estimated sensitivity of our definition of CHB infection. Results: The definition of CHB infection accurately identified clinician-confirmed cases (PPV, 96.3%; 95% confidence interval [CI], 87.3–99.5). Using this definition, 31,046 cases of CHB were diagnosed among 31,358,010 eligible Medicaid members from the five states (prevalence, 9.9 [95% CI, 9.8–10.0] per 10,000). Adjusting for the PPV and estimated sensitivity of our CHB definition, the prevalence of diagnosed CHB infection was 15.6 (95% CI, 15.4–15.7) per 10,000. Conclusions: Two outpatient CHB diagnoses recorded more than 6 months apart validly identified clinician-confirmed CHB. The prevalence of diagnosed CHB infection among U.S. Medicaid enrollees was 15.6 per 10,000. [Copyright &y& Elsevier]

Abstract: Background: A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons. Objectives: Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska. Study design: A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA<2000IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA≥2000IU/mL and ALT≥40IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation. Results: A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR)=2.41; 95% Confidence Interval (CI): 1.17–4.96), HBV DNA≥1000IU/mL at study entry (HR=7.61; 95% CI: 2.81–20.6), and HBV genotype B (HR=6.08; 95% CI: 1.32–28.0). Conclusions The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA≥1000IU/mL need to be followed-up more frequently. [Copyright &y& Elsevier]

Background/Aims: Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence ≥2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs). Methods: Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with ≥25% Asian patients in their practice were eligible. Results: Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed ≥200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that ≤25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that ≤50% of their adult Asian patients had received the HBV vaccine. Conclusions: Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed. [ABSTRACT FROM AUTHOR]

Background & Aims: Many foreign-born persons in the US are at high risk of chronic hepatitis B (HBV) and C (HCV) infections, yet are not aware of their infection, and lack healthcare coverage or linkage to care. Methods: A unique partnership, the Hepatitis Outreach Network, combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene, and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. Comprehensive HBV and HCV screening identifies infected patients, who then receive further evaluation from either local or Mount Sinai physicians, combined with patient-navigators who organize follow-up visits. Results: Of 1603 persons screened, 76 had HBV and 75 had HCV. Importantly, screening for HCV based on traditional risk factors would have missed 67% of those who tested positive. Of the 76 persons with HCV infection, 49 (64%) received a medical evaluation (26 with local providers and 23 at Mount Sinai). Of the 49 HCV-infected persons evaluated, treatment was recommended in 11 and begun in 8 (73%). Of the 76 persons with HBV infection, 43 (57%) received a medical evaluation (31 with local providers and 12 at Mount Sinai). Of the 43 HBV-infected persons evaluated, treatment was recommended and begun in 5 (100%). Conclusions: Hepatitis Outreach Network has successfully established novel proof of concept for identifying HBV and HCV infections in foreign-born persons through use of several unique elements that effectively link them to care. [Copyright &y& Elsevier]