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Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival. [ABSTRACT FROM AUTHOR]

Persons with isolated antibody to hepatits B virus (HBV) core antigen (IAHBc) may have occult HBV infection (OBI), which is associated with reactivation and potential risk for hepatocellular carcinoma and HBV transmission. We used National Health and Nutrition Examination Survey data to estimate US IAHBc prevalence and published studies of IAHBc-associated OBI prevalence to estimate OBI burden. During 2001-2018, the prevalence of IAHBc was 0.8% (approximately 2.1 million persons), and the OBI burden range was 35 500-83 600 persons. These data support the need for more robust estimates of IAHBc-associated OBI prevalence in the general US population. [ABSTRACT FROM AUTHOR]

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011–2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden. [ABSTRACT FROM AUTHOR]

In April 2015, the country of Georgia, with a high prevalence of hepatitis C virus (HCV) infection (5.4% of the adult population, approximately 150,000 persons), embarked on the world's first national elimination program (1,2). Nearly 40% of these infections are attributed to injection drug use, and an estimated 2% of the adult population currently inject drugs, among the highest prevalence of injection drug use in the world (3,4). Since 2006, needle and syringe programs (NSPs) have been offering HCV antibody testing to persons who inject drugs and, since 2015, referring clients with positive test results to the national treatment program. This report summarizes the results of these efforts. Following implementation of the elimination program, the number of HCV antibody tests conducted at NSPs increased from an average of 3,638 per year during 2006-2014 to an average of 21,551 during 2015-2018. In 2017, to enable tracking of clinical outcomes among persons who inject drugs, NSPs began encouraging clients to voluntarily provide their national identification number (NIN), which all citizens must use to access health care treatment services. During 2017-2018, a total of 2,780 NSP clients with positive test results for HCV antibody were identified in the treatment database by their NIN. Of 494 who completed treatment and were tested for HCV RNA ≥12 weeks after completing treatment, 482 (97.6%) were cured of HCV infection. Following the launch of the elimination program, Georgia has made much progress in hepatitis C screening among persons who inject drugs; recent data demonstrate high cure rates achieved in this population. Testing at NSPs is an effective strategy for identifying persons with HCV infection. Tracking clients referred from NSPs through treatment completion allows for monitoring the effectiveness of linkage to care and treatment outcomes in this population at high risk, a key to achieving hepatitis C elimination in Georgia. The program in Georgia might serve as a model for other countries. [ABSTRACT FROM AUTHOR]

Among 2338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 hepatitis B virus DNA level assessed annually. Among cirrhotic patients, 46% never had hepatic imaging. Patients in this cohort were insufficiently monitored for disease activity and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined.Methods: We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31).Results: All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection.Conclusions: Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years. [ABSTRACT FROM AUTHOR]

Background & Aims Information delineating the possible causes for elevated serum aminotransferase activity among persons with chronic hepatitis B virus (HBV) infection is limited. Methods We analysed data collected from a population-based cohort of persons with chronic HBV infection followed from 2001 to 2010 to determine the frequency and causes of elevated aminotransferase activity. Any elevation concurrent with an HBV DNA level ⩾2000 IU/ml was attributed to immune active hepatitis B. Participant medical charts were reviewed by expert clinical staff to determine the presence of additional or alternative attributable causes. For each participant, a serum aminotransferase elevation could be attributed to more than one cause. Results Among 1090 persons with chronic HBV infection, the mean follow-up was 7.7 years and the median age in 2001 was 39 (range 19–96) years; 634 (58.2%) had ⩾1 elevated aminotransferase level during follow-up and 438 (69.1%) of persons with ⩾1 elevation had at least one cause assigned for the elevation. The most common causes of aminotransferase elevations were immune active hepatitis B (48.4%), alcohol consumption (30.8%), and non-alcoholic fatty liver disease (NAFLD) (24.7%). Among participants with HBV DNA levels persistently less than 2000 IU/ml, the most common causes were NAFLD or alcohol consumption. Conclusions In this population-based cohort of persons with chronic HBV infection, the prevalence of elevated aminotransferase activity was high and attributable to immune active chronic hepatitis B in approximately half of the cases; however, NAFLD or alcohol consumption were also common causes for enzyme elevations. These findings underscore the importance of monitoring HBV DNA levels, in addition to aminotransferase activity, among persons with chronic HBV infection so that appropriate interventions, including antiviral therapy, are utilised. [ABSTRACT FROM AUTHOR]

Among persons in care during 2003–2010, we found that approximately 60% who tested positive for hepatitis C virus (HCV) antibody had a follow-up HCV RNA test to determine HCV infection status.Background. A test for hepatitis C virus (HCV) RNA is essential to identify persons with active, or current, HCV infection. We assessed trends in HCV RNA testing following a positive HCV antibody result among persons in 4 large healthcare organizations.Methods. Data collected from adults with ≥2 clinical encounters during 2003–2010 were analyzed to determine the frequency of, interval between, and factors associated with having an RNA test after a first positive HCV antibody test.Results. From 2003–2010, 5860 persons had a positive antibody test, of whom 3570 (60.9%) had a follow-up RNA test. During this period, the annual frequency of persons with an eventual RNA test did not change significantly; however, the fraction of persons who had the follow-up RNA test within 6 months improved significantly, from 45% in 2003 to 57% in 2010 (P < .001, for trend). Persons born during 1945–1965, men, and those with annual income <$30 000 (by census geocode) were less likely to have had a follow-up RNA test done within 6 months of a positive antibody test.Conclusions. Less than two-thirds of persons with a positive HCV antibody test had a follow-up RNA test. Rapid ascertainment of HCV infection status with reflex testing to RNA is critical to identify persons eligible for treatment. [ABSTRACT FROM AUTHOR]

The article presents a study which reviews medical literature and summarizes the evidence for seroprotection after hepatitis B vaccination among diabetics. It has been informed that hepatitis B vaccination is recommended for infants, children and young adults in the U.S., but no review has been published of its efficacy among diabetics.

Even among persons with access to care, many with 2 or more elevated ALT levels were not tested for HBV or HCV infection. Asian race and being middle-aged were independently associated with testing positive for HBV and HCV infection, respectively.Background. Little is known about viral hepatitis testing and infection prevalence among persons in private healthcare organizations (HCOs) in the United States.Methods. To determine the frequency of and characteristics associated with viral hepatitis testing and infection prevalence among adults with access to care, we conducted an observational cohort study among 1.25 million adults from 4 US HCOs and included persons with ≥1 clinical encounter during 2006–2008 and ≥12 months of continuous follow-up before 2009. We compared the number of infections identified with the number expected based on adjusted data from the National Health and Nutrition Examination Survey (NHANES).Results. Of 866 886 persons without a previous hepatitis B virus (HBV) diagnosis, 18.8% were tested for HBV infection, of whom 1.4% tested positive; among 865 659 without a previous hepatitis C virus (HCV) diagnosis, 12.7% were tested, of whom 5.5% tested positive. Less than half of those with ≥2 abnormal alanine aminotransferase (ALT) levels were subsequently tested for HBV or HCV. When tested, Asians (adjusted odds ratio [aOR] 6.33 relative to whites) were most likely HBV infected, whereas those aged 50–59 years were most likely HCV infected (aOR 6.04, relative to age <30 years). Based on estimates from NHANES, nearly one-half of HCV and one-fifth of HBV infections in this population were not identified.Conclusions. Even in this population with access to care and lengthy follow-up, only a fraction of expected viral hepatitis infections were identified. Abnormal ALT levels often but not consistently triggered testing. These findings have implications for the identification and care of 4–5 million US residents with HBV and HCV infection. [ABSTRACT FROM AUTHOR]

The article presents the study which evaluates hepatitis C virus (HCV) infection screening practices of patients with HIV infection in the HIV Outpatient Study (HOPS) from 1996-2007. The study also examines the trends in the prevalence of HCV infection in the HOPS. It found that HCV prevalence was reduced from 36.7% in 1996 to 19.7% in 2007. It concludes that screening for HCV infection in the HOPS has improved.

Objectives: In the United States, hepatitis C is the most commonly reported bloodborne infection. It is a leading cause of liver cancer and death from liver disease and imposes a substantial burden of hospitalization. We sought to describe regional differences in hepatitis C virus (HCV)–related hospitalizations during 2012 through 2019 to guide planning for hepatitis C elimination. Methods: We analyzed discharge data from the National Inpatient Sample for 2012 through 2019. We considered hospitalizations to be HCV-related if (1) hepatitis C was the primary diagnosis or (2) hepatitis C was any secondary diagnosis and the primary diagnosis was a liver disease–related condition. We analyzed demographic and clinical characteristics of HCV-related hospitalizations and modeled the annual percentage change in HCV-related hospitalization rates, nationally and according to the 9 US Census Bureau geographic divisions. Results: During 2012-2019, an estimated 553 900 HCV-related hospitalizations occurred in the United States. The highest hospitalization rate (34.7 per 100 000 population) was in the West South Central region, while the lowest (17.6 per 100 000 population) was in the West North Central region. During 2012-2019, annual hospitalization rates decreased in each region, with decreases ranging from 15.3% in the East South Central region to 48.8% in the Pacific region. By type of health insurance, Medicaid had the highest hospitalization rate nationally and in all but 1 geographic region. Conclusions: HCV-related hospitalization rates decreased nationally and in each geographic region during 2012-2019; however, decreases were not uniform. Expanded access to direct-acting antiviral treatment in early-stage hepatitis C would reduce future hospitalizations related to advanced liver disease and interrupt HCV transmission. [ABSTRACT FROM AUTHOR]

Hepatitis A is a vaccine‐preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person‐to‐person transmission have been widespread in the United States since 2016. We used public‐use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A‐listed deaths during non‐outbreak (2011–2015) and outbreak (2017–2021) periods and assessed the median age at death among decedents with and without hepatitis A‐listed deaths during the outbreak period. From the non‐outbreak period to the outbreak period, hepatitis A‐listed deaths more than doubled (from 369 to 801), while the hepatitis A‐listed age‐adjusted mortality rate increased 150% (p < 0.001). When compared with the non‐outbreak period, hepatitis A‐listed decedents during the outbreak period were more frequently male, aged 18–49 years, non‐Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A‐listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non‐outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A‐listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017–2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths. [ABSTRACT FROM AUTHOR]

We compared rates of emergency department visits and hospitalizations between patients with hepatitis C virus who achieved sustained virological response after direct-acting antiviral therapy (case patients) and matched controls. Among 3049 pairs, case patients demonstrated lower rates of liver-related emergency department visits (P = .01) than controls; all-cause and liver-related hospitalization rates and number of hospitalized days were also lower in case patients (P < . 001). [ABSTRACT FROM AUTHOR]

The article discusses two studies of hepatitis C in the U.S. carried out and analyzed by the Centers for Disease Control and Prevention's (CDC) Division of Viral Hepatitis as of May 2013. The Chronic Hepatitis Cohort Study (CHeCS) examines records from hepatitis C patients who have been seen at four health care organizations in the country since 2006. The National Health and Nutrition Examination Survey (NHANES) conducts random sampling of non-institutionalized civilians per year.

Background: After decades of decline, US acute hepatitis B incidence flattened since 2011. In persons aged ≥40 years and in jurisdictions affected by the opioid crisis, there is an increase in new cases. Data suggest new infections are occurring among US-born persons.Methods: We used National Health and Nutrition Examination Survey data during 2001-2018 to examine changes in total antibody to hepatitis B virus core antigen (anti-HBc) prevalence in US-born persons. During 2013-2018, the distribution of characteristics was examined.Results: During 2001-2006, 2007-2012, and 2013-2018, anti-HBc prevalence was 3.5%, 2.5%, and 2.6% among US-born persons, respectively. This corresponded to 5.7 (range, 4.8-6.6) million US-born persons with resolved or current HBV infection during 2013-2018, including 344 600 persons aged 6-29 years. The largest increase and highest prevalence was among persons who reported injection drug use (IDU), which increased from 35.3% during 2001-2006 to 58.4% during 2013-2018 (P = .07).Conclusions: Anti-HBc prevalence among US-born persons remained flat during the most recent period, coinciding with a doubling of prevalence among persons reporting IDU. These data are consistent with acute hepatitis B surveillance trends, showing increasing incidence in subpopulations where prevention could be strengthened.Anti-HBc prevalence among US-born persons decreased from 2001-2006 to 2007-2012 and remained flat during 2013-2018, coinciding with a near doubling of prevalence among US-born persons reporting a history of injection drug use. [ABSTRACT FROM AUTHOR]

Background Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents. Methods We analyzed 2000–2019 data from adults aged ≥18 years in the National Inpatient Sample. Hospitalizations were HCV-related if (1) hepatitis C was the primary diagnosis, or (2) hepatitis C was any secondary diagnosis with a liver-related primary diagnosis. We analyzed characteristics of HCV-related hospitalizations nationally and examined trends in age-adjusted hospitalization rates. Results During 2000–2019, there were an estimated 1 286 397 HCV-related hospitalizations in the United States. The annual age-adjusted hospitalization rate was lowest in 2019 (18.7/100 000 population) and highest in 2012 (29.6/100 000 population). Most hospitalizations occurred among persons aged 45–64 years (71.8%), males (67.1%), White non-Hispanic persons (60.5%), and Medicaid/Medicare recipients (64.0%). The national age-adjusted hospitalization rate increased during 2000–2003 (annual percentage change [APC], 9.4%; P <.001) and 2003–2013 (APC, 1.8%; P <.001) before decreasing during 2013–2019 (APC, −7.6%; P <.001). Comparing 2000 to 2019, the largest increases in hospitalization rates occurred among persons aged 55–64 years (132.9%), Medicaid recipients (41.6%), and Black non-Hispanic persons (22.3%). Conclusions Although multiple factors likely contributed, overall HCV-related hospitalization rates declined steadily after 2013, coinciding with the release of DAAs. However, the declines were not observed equally among age, race/ethnicity, or insurance categories. Expanded access to DAA treatment is needed, particularly among Medicaid and Medicare recipients, to reduce disparities and morbidity and eliminate hepatitis C as a public health threat. [ABSTRACT FROM AUTHOR]

Safe and effective hepatitis A vaccines have been recommended in the United States for at-risk adults since 1996; however, adult vaccination coverage is low. Among a random sample of adult outbreak-associated hepatitis A cases from three states that were heavily affected by person-to-person hepatitis A outbreaks, we assessed the presence of documented Advisory Committee on Immunization Practices (ACIP) indications for hepatitis A vaccination, hepatitis A vaccination status, and whether cases that were epidemiologically linked to an outbreak-associated hepatitis A case had received postexposure prophylaxis (PEP). Overall, 74.1% of cases had a documented ACIP indication for hepatitis A vaccination. Fewer than 20% of epidemiologically linked cases received PEP. Efforts are needed to increase provider awareness of and adherence to ACIP childhood and adult hepatitis A vaccination and PEP recommendations in order to stop the current person-to-person hepatitis A outbreaks and prevent similar outbreaks in the future. [ABSTRACT FROM AUTHOR]

Background: Since 2016, the United States has experienced person-to-person hepatitis A outbreaks unprecedented in the vaccine era. The proportion of cases hospitalized in these outbreaks exceeds historical national surveillance data.Methods: We described the epidemiology, characterized the reported increased morbidity, and identified factors associated with hospitalization during the outbreaks by reviewing a 10% random sample of outbreak-associated hepatitis A cases in Kentucky, Michigan, and West Virginia-3 heavily affected states. We calculated descriptive statistics and conducted age-adjusted log-binomial regression analyses to identify factors associated with hospitalization.Results: Participants in the random sample (n = 817) were primarily male (62.5%) with mean age of 39.0 years; 51.8% were hospitalized. Among those with available information, 73.2% reported drug use, 14.0% were experiencing homelessness, 29.7% were currently or recently incarcerated, and 61.6% were epidemiologically linked to a known outbreak-associated case. Residence in Michigan (adjusted risk ratio [aRR] = 1.8), being a man who has sex with men (aRR = 1.5), noninjection drug use (aRR = 1.3), and homelessness (aRR = 1.3) were significantly (P < .05) associated with hepatitis A-related hospitalization.Conclusions: Our findings support current Advisory Committee on Immunization Practices recommendations to vaccinate all persons who use drugs, men who have sex with men, and persons experiencing homelessness against hepatitis A. [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]

The role of ribavirin (RBV) in the era of direct‐acting antivirals (DAA) is not clear, and DAA studies have been largely genotype‐ and regimen‐specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir—all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one‐month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV‐free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Sustained virological response to treatment for chronic hepatitis C virus may improve short‐term glucose control among patients with type 2 diabetes, but the long‐term impact remains largely unknown. We used data from the Chronic Hepatitis Cohort Study to investigate the impact of sustained virological response on long‐term trends in haemoglobin A1c in patients with type 2 diabetes. Methods: "Index date" was defined as the date of treatment initiation (treated patients) or hepatitis C virus diagnosis (untreated patients). To address treatment selection bias, we used a propensity score approach. We used a piecewise, linear spline, mixed‐effects model to evaluate changes in haemoglobin A1c over a 5‐year period. Results: Our sample included 384 hepatitis C virus patients with type 2 diabetes (192 untreated, 192 treated, with sustained virological response or treatment failure). After adjusting for body mass index, haemoglobin A1c was stable among untreated and treatment failure patients. In sustained virological response patients, Hb1Ac trajectories evolved in three phases: (a) index through 6 months post‐index, average haemoglobin A1c decreased significantly from 7.7% to 5.4% per 90 days (P < 0.001); (b) 6‐30 months post‐index, haemoglobin A1c rebounded at a rate of 1.5% every 90 days (P = 0.003); and (c) from 30 months onward, haemoglobin A1c stabilized at an average level of 7.9 (P‐value = 0.34). Results from an analysis restricted to patients receiving direct‐acting antivirals were consistent with the main findings. Conclusion: Successful hepatitis C virus treatment among patients with type 2 diabetes significantly reduces HbA1c shortly after treatment, but these decreases are not sustained long‐term. Less than three years after sustained virological response, haemoglobin A1c rebounds to levels similar to untreated/treatment failure patients, and higher than recommended for type 2 diabetic maintenance. [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]

Summary: Background: The role of hepatitis C (HCV) eradication on the long‐term complications of type 2 diabetes mellitus remains incompletely studied. Aim: To investigate whether antiviral treatment impacted risk of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). Methods: We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine‐Gray subdistribution hazard ratio [sHR]), with death as a competing event. Results: Among 1395 HCV‐infected patients with type 2 diabetes, 723 (52%) were treated with either interferon‐based or direct‐acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end‐stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA‐treated patients and interferon‐treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause‐specific hazards, exclusion of patients with on‐treatment retinopathy, and treatment status as a time‐varying covariate. Conclusion: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Chronic hepatitis C virus (HCV)‐related complications have increased over the past decade. Methods: We used join‐point regression modelling to investigate trends in these complications from 2006 to 2015, and the impact of demographics on these trends. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we identified points at which the trend significantly changed, and estimated the annual percent change (APC) in rates of cirrhosis, decompensated cirrhosis and all‐cause mortality, adjusted by race, sex and age. Results: Among 11,167 adults with chronic HCV infection, prevalence of cirrhosis increased from 20.8% to 27.6% from 2006 to 2015, with adjusted annual percentage change (aAPC) of 1.2 (p <. 01). Although incidence of all‐cause mortality increased from 1.8% in 2006 to 2.9% in 2015, a join‐point was identified at 2010, with aAPCs of 9.6 before (2006 < 2010; p < .01) and −5.2 after (2010 ≤ 2015; p < .01), indicating a decrease in mortality from 2010 and onward. Likewise, overall prevalence of decompensated cirrhosis increased from 9.3% in 2006 to 10.4% in 2015, but this increase was confined to patients 60 or older (aAPC = 1.5; p = .023). Asian American and Black/African American patients demonstrated significantly higher rates of cirrhosis than White patients, while older patients and men demonstrated higher rates of cirrhosis and mortality. Conclusions: Although cirrhosis and mortality among HCV‐infected patients in the US have increased over the past decade, all‐cause mortality has decreased in recent years. [ABSTRACT FROM AUTHOR]

Background: Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting.Aim: Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C.Methods: Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk.Results: Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87).Conclusion: This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR. [ABSTRACT FROM AUTHOR]

Background: Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern.Aims: To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments.Methods: Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments.Results: Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%).Conclusions: ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients. [ABSTRACT FROM AUTHOR]

Background and Aims Antiviral therapy for patients with hepatitis B (HBV) infection is generally deferred for 'immune inactive' patients, although longitudinal changes in viral load and liver fibrosis remain understudied in this population. Likewise, in treated patients, the temporal relationship between changes in viral load and liver fibrosis is not well characterized. Using data from the chronic hepatitis cohort study, the study investigated viral load and the Fibrosis-4 index (FIB4, a serum-based marker of liver fibrosis) trajectories in both untreated and treated HBV patients. Materials and Methods We applied a bivariate, piecewise, linear spline, mixed-effects modeling approach to data from 766 HBV patients (342 untreated, 424 treated). Treatment selection bias was adjusted using propensity scores. Multiple sensitivity analyses were used to confirm results in untreated patients. Results Among all untreated patients, FIB4 began to increase by 0.9% per month (11% per year; P < 0.05) at 28 months post-index date, suggesting fibrosis progression. Significant FIB4 progression was also observed in a subgroup analysis of 'immune inactive' untreated patients. In treated patients, viral load declined 31.8% per month ( P < 0.05) for the first 5 months after treatment initiation, and 1.4-1.7% per month ( P < 0.05) thereafter. At 5 months after treatment initiation, FIB4 began to decline 0.5% per month ( P < 0.05), stabilizing at 28 months. Conclusion Among untreated HBV patients, FIB4 gradually increases over time, suggesting fibrosis progression, even in those patients designated as immune inactive. In treated patients, antiviral therapy results in a rapid decline in viral load followed by a delayed decline in markers of liver fibrosis. [ABSTRACT FROM AUTHOR]

During 1990-2019, universal infant and childhood vaccination for hepatitis B resulted in a 99% decline in reported cases of acute hepatitis B among children, adolescents, and young adults aged <19 years in the United States; however, during 2010-2019, cases of acute hepatitis B plateaued or increased among adults aged ≥40 years. We conducted a topical review of surveillance strategies that will be critical to support the elimination of hepatitis B as a public health threat in the United States. In 2019, notifiable disease surveillance for acute hepatitis B showed continued transmission, especially among people who inject drugs and people with multiple sexual partners; rates were highest among people who were aged 30-59 years, non-Hispanic White, and living in rural areas. In contrast, newly reported cases of chronic hepatitis B (CHB) were highest among people who were aged 30-49 years, Asian or Pacific Islander, and living in urban areas. The National Health and Nutrition Examination Survey documented the highest CHB prevalence among non–US-born, non-Hispanic Asian people during 2013-2018; only one-third of people with CHB were aware of their infection. In the context of universal adult vaccination (2022) and screening (2023) recommendations for hepatitis B, better data are needed to support programmatic strategies to improve (1) vaccination rates among people with behaviors that put them at risk for transmission and (2) screening and linkage to care among non–US-born people. Surveillance for hepatitis B needs to be strengthened throughout the health care and public health systems. [ABSTRACT FROM AUTHOR]

Background: Linking persons with hepatitis C virus (HCV) to care and treatment is critical to reduction in disease burden; typically, this entailed referral to a specialist. However, data regarding the frequency and factors associated with referral among patients in healthcare organizations (HCOs) are lacking.Methods: Among persons in four US HCOs with newly diagnosed HCV during 2006-2011, we determined the frequency of liver-related specialist care after diagnosis. We also identified sociodemographic and clinical characteristics associated with such care by multivariate analysis, adjusted for all variables.Results: Among 3592 patients with newly diagnosed HCV, 57 % (range among sites 45-90 %) received specialist care; of these, 57 % received care within 90 days of diagnosis. Patient characteristics associated with receipt of specialist care included: affiliation with one of the study sites [adjusted odds ratio (aOR) 4.8 vs. the referent site); having Medicare plus private insurance (aOR 1.6 vs. Medicaid); and having elevated alanine aminotransferase (ALT) (aOR 1.6 vs. normal ALT) or lower platelet values (aOR 1.4 vs. normal platelet level). Specialist care within 90 days of diagnosis was associated with private insurance (aOR 1.5 vs. Medicaid), elevated ALT levels (aOR 1.3-2.3 vs. normal), and having ≥2 comorbid conditions (aOR 1.4 vs. no comorbid conditions). Compared to patients not referred, those referred were more likely to be treated (aOR 3.5).Conclusions: Receipt of specialist care among persons with newly diagnosed HCV varied among HCOs. Clinical evidence of liver disease and having private insurance were associated with prompt receipt of specialist care and HCV treatment. [ABSTRACT FROM AUTHOR]

Background Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B ( CHB) in US general healthcare settings. Aim To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. Methods We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. Results Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen ( HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus ( HBV) DNA >2000 IU/ mL. Conclusions Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels. [ABSTRACT FROM AUTHOR]

Background & Aims Most regions of the world have ≤3 co-circulating hepatitis B virus ( HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma ( HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native ( AN) persons where five HBV genotypes (A, B, C, D, F) have been identified. Methods Our cohort comprised AN persons with chronic HBV infection identified during 1983-2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen ( HBeAg) testing and semi-annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status. Results Among the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person-years of follow-up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio ( aOR): 3.9, 95% confidence interval ( CI): 1.14-13.74], C ( aOR: 16.3, 95% CI: 5.20-51.11) and F ( aOR: 13.9, 95% CI: 5.30-36.69). Conclusion HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D. [ABSTRACT FROM AUTHOR]

Sustained virological response ( SVR) to antiviral therapy for hepatitis C ( HCV) reduces risk of hepatocellular carcinoma ( HCC), but there is little information regarding how treatment failure ( TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study ( CHe CS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure ( TF), and 1582 (43%) of these achieved sustained virological response ( SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio ( aHR) = 1.95, 95% confidence interval ( CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients ( aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality ( aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients). [ABSTRACT FROM AUTHOR]

Background: Guidelines for the treatment of HCV-infected persons were updated in August 2015 with new recommendations for patients with renal impairment. Treatment is imperative for patients with severe, renal-associated extrahepatic manifestations of HCV infection.Aims: We sought to describe the prevalence of these conditions among current HCV-infected patients in a population-based prospective, observational cohort study at four large US health systems.Methods: Data from cohort patients with chronic HCV infection during 2012 were analyzed for the period from 2006 to 2013. We determined the prevalence of mild to moderately impaired renal function defined as having the most recent estimated glomerular filtration rate [eGFR] ≤ 80 ml/min/1.73 m(2), with severe impairment defined as eGFR < 30 ml/min/1.73 m(2), based on the treatment guidelines. Prevalence of extrahepatic conditions was ascertained using ICD9-codes.Results: Among 5772 persons, the prevalence of eGFR ≤ 80 was 33 % and eGFR < 30 was 2 %, including among patients with hepatic fibrosis. Diagnosed extrahepatic renal manifestations were rare: vasculitis- 0.2 %, nephrotic syndrome- 0.3 %, and cryoglobulinemia- 0.9 %.Conclusions: While the prevalence of severe renal impairment and diagnosed extrahepatic manifestations was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom the need for treatment is urgent. [ABSTRACT FROM AUTHOR]

Background: The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In 1981, we immunized a cohort of 1578 Alaska Native adults and children from 15 Alaska communities aged ≥6 months using 3 doses of plasma-derived hepatitis B vaccine.Methods: Persons were tested for antibody to hepatitis B surface antigen (anti-HBs) levels 30 years after receiving the primary series. Those with levels <10 mIU/mL received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days after the booster.Results: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL. Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level ≥10 mIU/mL at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 30 years.Conclusions: Based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, we estimate that ≥90% of participants had evidence of protection 30 years later. Booster doses are not needed. [ABSTRACT FROM AUTHOR]

Background. A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. Methods. This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. Results. Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. Conclusions. The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease. [ABSTRACT FROM AUTHOR]

Background. The American Association for the Study of Liver Diseases (AASLD) recommends semi-annual hepatocellular carcinoma (HCC) screening using ultrasound (US) in persons with chronic hepatitis B (CHB) virus infection at high risk for HCC such as Asian males aged ]40 years and Asian females aged ]50 years. Objective. To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN) health system: US-alone, or screening by alpha-fetoprotein (AFP) initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP → US). Design. A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983--2012. We assumed that compared with AFP 0US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter). Years of life gained (YLG) attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. Results. The total cost of screening for the cohort by AFP 0US would have been approximately $357,000 ($36,000/early-stage tumour detected) compared to $814,000 ($59,000/early-stage tumour detected) by US-alone. The AFP → US method would have yielded an additional 27.8 YLG ($13,000/YLG) compared with 38.9 YLG ($21,000/YLG) for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP 0US and $41,000 per extra YLG. Conclusions. Although US-alone HCC screening might have yielded more YLG than AFP 0US, the reduced costs of the AFP 0US method could expand access to HCC screening in resource constrained settings. [ABSTRACT FROM AUTHOR]

Background. There have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations. Objective. To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population. Design. In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. Results. Sustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p =0.002), estimated duration of infection (p =0.034) and HCV genotype (p B0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%). Conclusions. We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1. [ABSTRACT FROM AUTHOR]

Objectives:The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker.Methods:Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling.Results:Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P<0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis.Conclusions:A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed. [ABSTRACT FROM AUTHOR]

Highlights: [•] This report describes response to hepatitis B vaccination after assisted living facility outbreak. [•] 61 susceptible residents aged 46–86 received TWINRIX™ at 0, 1, 7 months. [•] 27 (44%) vaccinated residents consented to measurement of vaccine response. [•] Among those tested, 22 (81%) achieved seroprotection measured by anti-HBs ≥10mIU/mL. [•] Even those over age 60 showed a robust capacity for achieving seroprotection. [Copyright &y& Elsevier]

The genetic characterization of hepatitis A virus (HAV) strains is commonly accomplished by sequencing subgenomic regions, such as the VP1/P2B junction. HAV genome is not extensively variable, thus presenting opportunity for sharing sequences of subgenomic regions among genetically unrelated isolates. The degree of misrepresentation of phylogenetic relationships by subgenomic regions is especially important for tracking transmissions. Here, we analyzed whole-genome (WG) sequences of 101 HAV strains identified from 4 major multi-state, food-borne outbreaks of hepatitis A in the Unites States and from 14 non-outbreak-related HAV strains that shared identical VP1/P2B sequences with the outbreak strains. Although HAV strains with an identical VP1/P2B sequence were specific to each outbreak, WG were different, with genetic diversity reaching 0.31% (mean 0.09%). Evaluation of different subgenomic regions did not identify any other section of the HAV genome that could accurately represent phylogenetic relationships observed using WG sequences. The identification of 2–3 dominant HAV strains in 3 out of 4 outbreaks indicates contamination of the implicated food items with a heterogeneous HAV population. However, analysis of intra-host HAV variants from eight patients involved in one outbreak showed that only a single sequence variant established infection in each patient. Four non-outbreak strains were found closely related to strains from 2 outbreaks, whereas ten were genetically different from the outbreak strains. Thus, accurate tracking of HAV strains can be accomplished using HAV WG sequences, while short subgenomic regions are useful for identification of transmissions only among cases with known epidemiological association. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. Methods: We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. Results: No significant differences were observed when comparing GMC between the two cohorts at 10 (P =0.467), 12 (P =0.496), and 14 (P =0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years. Conclusion: The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term. [Copyright &y& Elsevier]

Baseline demographic, clinical, and mortality data from the Chronic Hepatitis Cohort Study utilize the electronic health records of >2200 chronic hepatitis B virus and 8800 chronic hepatitis C virus patients from 4 integrated healthcare systems and highlight the substantial US health burden from chronic viral hepatitis.Background. The Chronic Hepatitis Cohort Study (CHeCS), a dynamic prospective, longitudinal, observational cohort study, was created to assess the clinical impact of chronic viral hepatitis in the United States. This report describes the cohort selection process, baseline demographics, and insurance, biopsy, hospitalization, and mortality rates.Methods. Electronic health records of >1.6 million adult patients seen from January 2006 through December 2010 at 4 integrated healthcare systems in Detroit, Michigan; Danville, Pennsylvania; Portland, Oregon; and Honolulu, Hawaii were collected and analyzed.Results. Of 2202 patients with chronic hepatitis B virus (HBV) infection, 50% were aged 44–63 years, 57% male, 58% Asian/Pacific Islander, and 13% black; and 5.1% had Medicaid, 16.5% Medicare, and 76.3% private insurance. During 2001–2010, 22.3% had a liver biopsy and 37.9% were hospitalized. For the 8810 patients with chronic hepatitis C virus (HCV) infection, 75% were aged 44–63 years, 60% male, 23% black; and 12% had Medicaid, 23% Medicare, and 62% private insurance. During 2001–2010, 38.4% had a liver biopsy and 44.3% were hospitalized. Among persons in care, 9% of persons with HBV and 14% of persons with HCV infection, mainly those born during 1945–1964, died during the 2006–2010 five-year period.Conclusions. Baseline demographic, hospitalization, and mortality data from CHeCS highlight the substantial US health burden from chronic viral hepatitis, particularly among persons born during 1945–1964. [ABSTRACT FROM AUTHOR]

Abstract: Protection of older persons, particularly those with diabetes, against hepatitis B virus (HBV) infection is of growing concern because of increased reports of outbreaks among long-term care facility residents receiving assisted blood glucose monitoring. We evaluated hepatitis B vaccine immunogenicity among residents immunized in response to two such outbreaks in skilled nursing facilities during June 2009–July 2010. One hundred forty-eight (71%) of 209 residents were found to be susceptible to HBV infection. Of 105 patients who began a vaccination series with Twinrix® (0-, 1-, 6-month dosing), 86 (82%) completed the series and postvaccination testing. Of these, most were elderly (median age 79.5 years; range 45–101), female (56%), and African-American (51%). Twenty-nine (34%) vaccinated residents had post-vaccination hepatitis B surface antibody levels ≥10mIU/ml. There were no significant differences in vaccine response by age, gender, race, diabetes status, body mass index, or current smoking status. Our findings indicate that a low proportion of skilled nursing facility residents achieved a seroprotective response after hepatitis B vaccination. [Copyright &y& Elsevier]

The article summarizes the recommendations from the Advisory Committee on Immunication Practices (ACIP) regarding the use of Hepatitis B vaccination for adults with diabetes mellitus. Data from Emerging Infections Program (EIP) sites and the National Health and Nutrition Examination Survey (NHANES) reveal the population risk for Hepatitis B Virus (HBV) infection among adults with diabetes. Hepatitis B vaccines available in the U.S. are the single-antigen recombinant Recombivax HB and Engerix-B vaccines, and the Twinrix hepatitis A and B combination vaccine. The ACIP recommends the administration of Hepatitis B vaccine unvaccinated diabetic adults aged 19-59, while those aged 60 and beyond could be vaccinated at the discretion of the treating clinician.

Abstract: Background: During the past decade, in the United States, an increasing number of hepatitis B outbreaks have been reported in assisted living facilities (ALFs) as a result of breaches in infection control practices. We evaluated the seroprotection rates conferred by hepatitis B vaccine among older adults during a response to an outbreak that occurred in multiple ALFs and assessed the influence of demographic and clinical factors on vaccine response. Methods: Residents were screened for hepatitis B and C infection prior to vaccination and susceptible residents were vaccinated against hepatitis B with one dose of 20μg Engerix-B™ (GSK) given at 0, 1, and 4months. Blood samples were collected 80–90days after the third vaccine dose to test for anti-HBs levels. Results: Of the 48 residents who had post-vaccination blood specimens collected after the third vaccine dose, 16 (33.3%) achieved anti-HBs concentration ≥10mIU/mL. Age was a significant determinant of seroprotection with rates decreasing from 88% among persons aged ≤60years to 12% among persons aged ≥90years (p =0.001). Geometric mean concentrations were higher among non-diabetic than diabetic residents, however, the difference was not statistically significant (5.1 vs. 3.8mIU/mL, p =0.7). Conclusions: These findings highlight that hepatitis B vaccination is of limited effectiveness when administered to older adults. Improvements in infection control and vaccination at earlier ages might be necessary to prevent spread of infection in ALFs. [Copyright &y& Elsevier]