Epidemiologic data regarding persons with active tuberculosis (TB) and chronic hepatitis B virus (cHBV) infection are limited because of lack of routine surveillance of cHBV in persons with TB. Potential underdiagnosis of cHBV in California among those with TB is concerning. We matched TB and cHBV registries to identify cHBV infections among persons diagnosed with TB during 2016-2020 and described their demographic characteristics. We calculated expected cHBV cases among persons with TB for each demographic characteristic using published cHBV prevalence estimates for the locations of birth for persons with TB. Estimates were from general or emigrant adult and teen populations. Reported cHBV infection among persons with TB were 23% lower than expected, particularly among Asian persons, persons living in the two healthiest Healthy Places Index quartiles, and residents of less populated jurisdictions in California. Results show the possibility exists for underdiagnosis of cHBV in persons with TB in California.

BACKGROUND: Improved epidemiologic and treatment data for active tuberculosis (TB) with chronic hepatitis B virus (cHBV) infection might inform and encourage screening and vaccination programs focused on persons at risk of having both conditions. METHODS: We matched the California Department of Public Health TB registry during 2016-2020 to the cHBV registry using probabilistic matching algorithms. We used chi-square analysis to compare the characteristics of persons with TB and cHBV with those with TB only. We compared TB treatment outcomes between these groups using modified Poisson regression models. We calculated the time between reporting of TB and cHBV diagnoses for those with both conditions. RESULTS: We identified 8,435 persons with TB, including 316 (3.7%) with cHBV.- Among persons with TB and cHBV, 256 (81.0%) were non-U.S.-born Asian vs 4,186 (51.6%) with TB only (P <0.0001). End-stage renal disease (26 [8.2%] vs 322 [4.0%]; P <0.001) and HIV (21 [6.7%] vs 247 [3.0%]; P value = 0.02) were more frequent among those with TB and cHBV compared with those with TB only. Among those with both conditions, 35 (11.1%) had TB diagnosed >60 days before cHBV (median 363 days) and 220 (69.6%) had TB diagnosed >60 days after cHBV (median 3,411 days). CONCLUSION: Persons with TB and cHBV were found more frequently in certain groups compared with TB only, and infrequently had their conditions diagnosed together. This highlights an opportunity to improve screening and treatment of TB and cHBV in those at high risk for coinfection.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request.

Adults at increased risk for hepatitis B virus (HBV) infection are recommended to receive vaccination. We conducted a cost utility analysis to evaluate approaches for implementing that recommendation in selected high-risk settings: community outreach events with a large proportion of immigrants, syringe service programs, substance use treatment centers, sexually transmitted infection (STI) clinics, tuberculosis (TB) clinics, and jails. We utilized a decision tree framework with a Markov disease progression model to compare quality adjusted life-years and cost in 2021 United States dollars from four strategies: a 3-dose vaccination regimen with prevaccination screening and testing (PVST; baseline comparison); PVST at the initial encounter followed by a 2-dose series (Intervention 1); PVST with the first dose of a 2-dose vaccination series at the initial encounter (Intervention 2); and a 2-dose vaccination series without PVST (Intervention 3). In all settings, Intervention 1 resulted in worse health outcomes compared to the baseline strategy. Intervention 2 averted incident chronic HBV infections in all settings (range -9.4% in TB clinics, -14.8% in syringe service programs) and was a cost-saving approach in settings with higher risk of infection (i.e. jails, -$266 per person; syringe service programs, -$597; substance use treatment centers, -$130). Providing a 2-dose vaccination series without any screening (Intervention 3) averted incident HBV infections and was cost-saving in all settings, but resulted in more HBV-related deaths in settings with higher HBV prevalence. These results demonstrate a 2-dose vaccine series is a cost-effective approach in these high impact settings, even if prevaccination testing is not possible.

During 1995-2011, the overall incidence of hepatitis A decreased by 95% in the United States from 12 cases per 100,000 population during 1995 to 0.4 cases per 100,000 population during 2011, and then plateaued during 2012─2015. The incidence increased by 294% during 2016-2018 compared with the incidence during 2013-2015, with most cases occurring among populations at high risk for hepatitis A infection, including persons who use illicit drugs (injection and noninjection), persons who experience homelessness, and men who have sex with men (MSM) (1-3). Previous outbreaks among persons who use illicit drugs and MSM led to recommendations issued in 1996 by the Advisory Committee on Immunization Practices (ACIP) for routine hepatitis A vaccination of persons in these populations (4). Despite these long-standing recommendations, vaccination coverage rates among MSM remain low (5). In 2017, the New York City Department of Health and Mental Hygiene contacted CDC after public health officials noted an increase in hepatitis A infections among MSM. Laboratory testing* of clinical specimens identified strains of the hepatitis A virus (HAV) that subsequently matched strains recovered from MSM in other states. During January 1, 2017-October 31, 2018, CDC received reports of 260 cases of hepatitis A among MSM from health departments in eight states, a substantial increase from the 16 cases reported from all 50 states during 2013-2015. Forty-eight percent (124 of 258) of MSM patients were hospitalized for a median of 3 days. No deaths were reported. In response to these cases, CDC supported state and local health departments with public health intervention efforts to decrease HAV transmission among MSM populations. These efforts included organizing multistate calls among health departments to share information, providing guidance on developing targeted outreach and managing supplies for vaccine campaigns, and conducting laboratory testing of clinical specimens. Targeted outreach for MSM to increase awareness about hepatitis A infection and improve access to vaccination services, such as providing convenient locations for vaccination, are needed to prevent outbreaks among MSM.

A suspected outbreak of influenza A and SARS-CoV-2 at a long-term care facility in Los Angeles County was months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow CDC guidelines that specifically address infection control challenges.

Following increases in reported cases of hepatitis A, we assessed the impact of hepatitis A vaccine in Alaska Native persons. During 1996-2018, only 6 cases of hepatitis A were identified, all in unvaccinated adults. Populations can be protected against hepatitis A by achieving sufficient vaccination coverage over time.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required.

BACKGROUND: In Alaska, while introduction of 13-valent pneumococcal conjugate vaccine led to declines in invasive pneumococcal disease, carriage prevalence remained stable because of replacement with non-vaccine serotypes. We assessed antibiotic non-susceptibility of carried pneumococci during serotype redistribution, determined the contributions of within-serotype shifts, and assessed factors that could explain changes in non-susceptibility. METHODS: Each year from 2008 to 2015, at multiple sites in Alaska, we collected nasopharyngeal swabs and completed surveys for a convenience sample of participants. Pneumococcal serotyping and antimicrobial susceptibility testing for penicillin and erythromycin were performed. We described changes in non-susceptibility of isolates from 2008-2011 to 2012-2015, and assessed the contributions of serotype redistribution and within-serotype changes in non-susceptibility by comparing observed data to modeled data removing either factor. We used weighted logistic regression to assess whether reported risk factors could explain changes over time in non-susceptibility within serotypes. RESULTS: From 2008-2011 to 2012-2015, the overall proportion of isolates non-susceptible to penicillin or erythromycin increased by 3%, from 23% (n = 1,183) to 26% (n = 1,589; P < 0.05). However, a decrease of 3% would be expected if serotype redistribution occurred without within-serotype changes in non-susceptibility. Standardization by either factor produced hypothetical data significantly different to observed data. Within serotypes, the average annual increase in odds of non-susceptibility to penicillin or erythromycin was 1.08 (95% CI 1.05-1.11). Recent antibiotic exposure, urban residence and increased household size of participants predicted isolate non-susceptibility but did not explain the increase over time. DISCUSSION: An overall increase in non-susceptibility of carried pneumococcal isolates to penicillin or erythromycin resulted from increases in non-susceptibility within serotypes, which outweighed a protective effect of serotype redistribution. Characterization of emerging resistant clones within carried non-vaccine serotypes, including risk factors for colonization and disease, would support disease prevention efforts and inform vaccine strategies.

Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.

Most persons with chronic HCV infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients with HCV infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) compared to national estimates (approximately 25%).

We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.

OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR>5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0*1-0*3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.

We identified risk factors for any emm-type group A streptococcal (GAS) colonization while investigating an invasive emm26.3 GAS outbreak among people experiencing homelessness in Alaska. Risk factors included upper extremity skin breakdown, sleeping outdoors, sharing blankets, and infrequent tooth brushing. Our results may help guide control efforts in future outbreaks.

In the United States, the incidence of hepatitis A virus (HAV) infection has been reduced through universal childhood vaccination. However, the duration of immunogenicity for the hepatitis A vaccine is not known. We report on the 22 year follow-up time point of a cohort of Alaska children who were randomized to three different vaccine schedules: A) 0,1,2 months; B) 0,1,6 months; and C) 0,1,12 months. Among 46 participant available for follow-up, 40 (87%) maintained protective levels of anti-hepatitis A antibody. These results indicate that a supplemental booster dose is not yet necessary at or before the 22-year time point. This article is protected by copyright. All rights reserved.

Background: In 2016, we detected an outbreak of group A Streptococcus (GAS) invasive infections among the estimated 1000 persons experiencing homelessness (PEH) in Anchorage, Alaska. We characterized the outbreak and implemented a mass antibiotic intervention at homeless service facilities. Methods: We identified cases through the Alaska GAS laboratory-based surveillance system. We conducted emm typing, antimicrobial susceptibility testing, and whole-genome sequencing on all invasive isolates and compared medical record data of patients infected with emm26.3 and other emm types. In February 2017, we offered PEH at 6 facilities in Anchorage a single dose of 1 g of azithromycin. We collected oropharyngeal and nonintact skin swabs on a subset of participants concurrent with the intervention and 4 weeks afterward. Results: From July 2016 through April 2017, we detected 42 invasive emm26.3 cases in Anchorage, 35 of which were in PEH. The emm26.3 isolates differed on average by only 2 single-nucleotide polymorphisms. Compared to other emm types, infection with emm26.3 was associated with cellulitis (odds ratio [OR], 2.5; P = .04) and necrotizing fasciitis (OR, 4.4; P = .02). We dispensed antibiotics to 391 PEH. Colonization with emm26.3 decreased from 4% of 277 at baseline to 1% of 287 at follow-up (P = .05). Invasive GAS incidence decreased from 1.5 cases per 1000 PEH/week in the 6 weeks prior to the intervention to 0.2 cases per 1000 PEH/week in the 6 weeks after (P = .01). Conclusions: In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic administration was temporally associated with reduced invasive disease cases and colonization prevalence.

BACKGROUND: The pneumococcal conjugate vaccine (PCV) was introduced in 2001. Widespread PCV use nearly eradicated pneumococcal colonization by vaccine serotypes. Since 2008, however, colonization by PCV-serotype 19F has increased in Alaska residents. We describe the epidemiology of re-emerging serotype 19F colonization. METHODS: We conducted annual cross-sectional colonization surveys from 2008 to 2013. We recruited children aged <5years at 2 urban clinics and participants of all ages from Region-A (2 villages), Region-B (4 villages), and Region-C (2 villages). We interviewed participants and reviewed their medical records to obtain demographic information and determine PCV status. We obtained nasopharyngeal swab specimens from participants to identify pneumococci and to determine the pneumococcal serotype, antimicrobial resistance, and multilocus sequence type. We used the Cochran-Armitage test to assess for significant trends in colonization across time periods. RESULTS: Among participants aged <5years, pneumococcal serotype 19F colonization remained unchanged from 2008-2009 (0.7%) to 2012-2013 (0.5%; P-value [P]=.54). Serotype 19F colonization increased from 2008-2009 to 2012-2013 among participants aged 5-11years (0.3% to 3.2%; P<.01), participants 12-17years (0.0% to 2.0%; P<.01), and participants aged >/=18years (0.1% to 0.5%; P<.01). During 2012-2013, 85 (93%) of 91 pneumococcal serotype 19F isolates were identified among participants from Region B; the majority of serotype 19F isolates belonged to an antimicrobial nonsusceptibility pattern corresponding to a novel multilocus sequence type 9074. CONCLUSIONS: PCV continues to protect against serotype 19F colonization in vaccinated children aged <5years. The direct PCV impact on serotype 19F colonization in persons aged 5-11years and indirect impact in persons aged >/=12years is waning, possibly because of a newly introduced genotype in Region-B.

In 2010, the World Health Organization (WHO) and the US Advisory Committee on Immunization Practices (ACIP) recommended the use of the 13-valent pneumococcal conjugate vaccine (PCV13) for children aged 6 weeks to 71 months in schedules of 3 primary infant doses (3 + 0), 3 doses with a booster after 1 year of age (3 + 1), or 2 primary infant doses with booster (2 + 1) [1, 2]. | In countries where PCV13 use has eliminated vaccine-type disease, experts question whether a 1- or 2-dose PCV13 schedule is sufficient to maintain indirect protection [3]. In immunogenicity studies, 81%–100% of children demonstrated sufficient antipolysaccharide immunoglobulin after 1 infant dose [4]. However, studies of clinical outcomes have been inconclusive. In a case-control study in the United States, low numbers of cases prevented investigators from calculating relative odds of invasive disease between partial dose groups [5]. Carriage studies can provide another marker of vaccine effectiveness, although comparisons of full and reduced PCV13 schedules and carriage have not been reported.

Long-term prospective studies of the outcomes associated with HCV infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a start point, we looked at development of end stage liver disease (ESLD), hepatocellular carcinoma (HCC) and liver-related death (LRD) according to fibrosis stage, among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak=0,1), moderate (Ishak=2), or severe (Ishak=3,4) fibrosis or cirrhosis (Ishak=5,6). We examined time until development of ESLD, HCC and LRD and report survival probabilities at 3, 5, 7 and 10-years. Of 407 persons, 39%(n = 150) had no/mild fibrosis, 32%(n = 131) had moderate fibrosis, 22%(n = 88) had severe fibrosis and 9%(n = 38) had cirrhosis. The average time of follow-up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval (CI):0.4,6.8) of persons with none/mild fibrosis developed ESLD compared to 7.9% (CI:4.0,15.2), 16.4% (CI:9.6,27.2) and 49.0% (CI:33.0,67.7) with moderate, severe fibrosis, and cirrhosis, respectively (p<0.01). The 5-year outcome of HCC was 1.0% (CI:0.1,7.0), 1.0% (CI 0.1,6.6), 1.1% (CI:0.2,7.7) and 13.4% (CI:4.4,36.7) among persons with none/mild, moderate fibrosis, severe fibrosis and cirrhosis, respectively (p<0.01). Five years following biopsy, 0.0% (CI:0.0,14.8) of persons with none/mild fibrosis had suffered an LRD compared to 1.0% (CI:0.2,7.5) of persons with moderate fibrosis, 4.7% (CI:1.5,14.1) with severe fibrosis and 16.3% (CI:7.0,35.1) with cirrhosis (p<0.01). Conclusion For prevention of HCC, LRD and ESLD in the short-term, HCV therapy should target those with more than mild fibrosis. This article is protected by copyright. All rights reserved.

OBJECTIVE: Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. METHODS: We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. RESULTS: ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). CONCLUSIONS: A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons.

Sirs, We appreciate the interest in our study from Professors Chen and Liaw and the opportunity to provide additional information.1 As we acknowledged in our paper, the wide confidence intervals for our risk estimates resulting from the relatively small number of case- and control-patients developing HCC were an important limitation to our study.2 Thus, it is possible that we failed to detect a real reduction in HCC risk because of insufficient statistical power. As requested, we recalculated the risk for developing HCC after excluding the 2 case-patients who received antiviral treatment before HBsAg seroclearance and the 32 control-patients who had received antiviral treatment. After adjusting for age at cohort entry and initial anti-hepatitis B e antibody status, we did not detect a difference in HCC risk among case-compared with control-patients after excluding patients who had received antiviral treatment (adjusted hazard ratio: 0.7; 95% confidence interval: 0.2–2.7). The effect of age at HBsAg seroclearance on risk for HCC is complex and could be partly related to the specific HBV genotypes represented in a population. It has been demonstrated that the duration of hepatitis B e antigen persistence and the risk for HCC is substantially higher for persons with HBV genotype C compared with other genotypes.3,4 The majority of patients in the study indicating an increased risk for HCC among persons aged ≥50 years at the time of HBsAg seroclearance were infected with HBV genotype C.5,6 In contrast, the majority of patients in our study population were infected with HBV genotype D. Therefore, the risk for HCC associated with a later age of HBsAg seroclearance among Alaska Native persons compared with other geographic regions is unclear because of differences in the prevalence of HBV genotypes. Furthermore, the age at HBsAg seroclearance should not affect our interpretation of the relative risk for HCC between case- and control-patients because the majority of participants acquired HBV infection in early childhood and our analysis adjusted for case-patients’ HBsAg duration prior to seroclearance. We also speculated in our paper that ongoing low-level HBV DNA replication with continued integration into the host hepatocyte could have contributed to persistent HCC risk after HBsAg seroclearance. Further study is necessary to determine the relative importance of HBV viremia early in the course of disease versus persistence of viremia after HBsAg clearance in the development of HCC.

Objective: The U.S. Agency for Healthcare Research and Quality's Prevention Quality Indicators comprise acute and chronic conditions for which hospitalization can be potentially prevented by high-quality ambulatory care. The Healthy Alaska 2020 initiative (HA2020) targeted reducing potentially preventable hospitalizations (PPH) for acute and chronic conditions among its health indicators. We estimated the PPH rate for adults aged ≥ 18 years in Alaska during 2010-2012. Methods: We conducted a cross-sectional analysis of state-wide hospital discharge data obtained from the Healthcare Cost and Utilization Project and the Indian Health Service. We calculated average annual PPH rates/1000 persons for acute/chronic conditions. Age-adjusted rate ratios (aRRs) were used for evaluating PPH rate disparities between Alaska Native (AN) and non-AN adults. Results: Among 127,371 total hospitalizations, 4911 and 6721 were for acute and chronic PPH conditions, respectively. The overall crude PPH rate was 7.3 (3.1 for acute and 4.2 for chronic conditions). AN adults had a higher rate than non-AN adults for acute (aRR: 4.7; . p < 0.001) and chronic (aRR: 2.6; p < 0.001) PPH conditions. Adults aged ≥ 85. years had the highest PPH rate for acute (43.5) and chronic (31.6) conditions. Acute conditions with the highest PPH rate were bacterial pneumonia (1.8) and urinary tract infections (0.8). Chronic conditions with the highest PPH rate were chronic obstructive pulmonary disease (COPD; 1.6) and congestive heart failure (CHF; 1.3). Conclusion: Efforts to reduce PPHs caused by COPD, CHF, and bacterial pneumonia, especially among AN people and older adults, should yield the greatest benefit in achieving the HA2020 goal.

BACKGROUND: The aspartate aminotransferase-to-platelet ratio index (APRI) and a fibrosis index calculated using platelets (FIB-4) have been proposed as noninvasive markers of liver fibrosis. GOALS: To determine APRI/FIB-4 accuracy for predicting histologic liver fibrosis and evaluate whether incorporating change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska Native persons. STUDY: Using liver histology as the gold standard, we determined the test characteristics of APRI to predict Metavir ≥F2 fibrosis and FIB-4 to predict Metavir ≥F3 fibrosis. Index discrimination was measured as the area under the receiver operator characteristic curve. We fit a logistic regression model to determine whether incorporating change in APRI/FIB-4 over time improved index discrimination. RESULTS: Among 283 participants, 46% were female, 48% had a body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%). On liver histology, 30% of study participants had ≥F2 fibrosis and 15% had ≥F3 fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was 91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB-4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did not improve index discrimination. CONCLUSIONS: The accuracy of APRI/FIB-4 for identifying liver fibrosis in HCV-infected Alaska Native persons is similar to that reported in other populations and could help prioritize patients for treatment living in areas without access to liver biopsy. Change in APRI/FIB-4 was not predictive of degree of fibrosis.

BACKGROUND & AIMS: Few studies have examined factors associated with disease progression in hepatitis C virus (HCV) infection. We examined the association of 11 risk factors with adverse outcomes in a population-based prospective cohort observational study of Alaska Native/American Indian persons with chronic HCV infection. METHODS: We collected data from a population-based cohort study of liver-related adverse outcomes of infection in American Indian/Alaska Native persons with chronic HCV living in Alaska, recruited from 1995 through 2012. We calculated adjusted hazard ratios (aHR) and 95% CIs for end-stage liver disease (ESLD; presence of ascites, esophageal varices, hepatic encephalopathy, or coagulopathy), hepatocellular carcinoma (HCC), and liver-related death using a Cox proportional hazards model. RESULTS: We enrolled 1080 participants followed for 11,171 person-years (mean, 10.3 years); 66%, 19%, and 14% were infected with HCV genotypes 1, 2, and 3, respectively. On multivariate analysis, persons infected with HCV genotype 3 had a significantly increased risk of developing all 3 adverse outcomes. Their aHR for ESLD was 2.1 (95% CI, 1.5-3.0), aHR for HCC was 3.1 (95% CI, 1.4-6.6), and aHR for liver-related death was 2.4 (95% CI, 1.5-4.0) compared to genotype 1. Heavy alcohol use was an age-adjusted risk factor for ESLD (aHR, 2.2; 95% CI, 1.6-3.2), and liver-related death (aHR: 2.9; 95% CI, 1.8-4.6). Obesity was a risk factor for ESLD (aHR, 1.4; 95% CI, 1.0-1.9, and diabetes was a risk factor for ESLD (aHR, 1.5; 95% CI, 1.1-2.2). Male sex was a risk factor for HCC (aHR, 3.6; 95% CI, 1.6-8.2). CONCLUSIONS: In a population-based cohort study of American Indian/Alaska Native persons with chronic HCV infection, we found those infected with HCV genotype 3 to be at high risk for ESLD, HCC, and liver-related death.

OBJECTIVES: To evaluate the hepatocellular carcinoma (HCC) risk in Alaska Native children and young adults with hepatitis B virus (HBV). STUDY DESIGN: Retrospective analysis of a population-based cohort of Alaska Native persons with HBV followed during 1982-2012. All individuals with HBV were offered HCC screening regardless of age using alpha-fetoprotein every 6 months; persons with an elevated alpha-fetoprotein or persons at high-risk for HCC, such as cirrhosis, family history of HCC, were offered ultrasound. We calculated the HCC incidence/1000 person-years from date of cohort entry until death, diagnosis of HCC, or attaining the age of 40 years (males) or 50 years (females). RESULTS: We followed 1083 subjects with HBV (56% male) comprising 5 genotypes (A2 [12.5%], B6 [1.7%], C [5.3%], D [49.7%], F1 [18.6%], unknown [12.4%]) for a median of 23.4 years/person. We observed 22 HCC cases (incidence/1000 person-years follow-up: 1.0); 19 HCC cases among persons with genotype F1. There was no significant difference in HCC incidence between males (1.4) and females (0.6). The HCC incidence was significantly higher for persons with genotype F1 (4.4) compared with genotype A2 (0.4) and D (0.2) and remained higher among persons with HBV genotype F1 excluding persons with HCC family history/cirrhosis (1.9). CONCLUSIONS: Alaska Native children and young adults with HBV genotype F1 are at high risk for HCC and should receive HCC surveillance. For males <40 years of age and females <50 years of age with HBV in regions of the world with a high genotype F prevalence, testing/confirming genotype F can identify persons who could benefit from HCC surveillance.

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-->US, 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-->US 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-->US and $41,000 per extra YLG. CONCLUSIONS: Although US-alone HCC screening might have yielded more YLG than AFP-->US, the reduced costs of the AFP-->US method could expand access to HCC screening in resource constrained settings.

BACKGROUND: Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear. AIM: To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance. METHODS: We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model. RESULTS: The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03). CONCLUSIONS: Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.

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 5 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 the study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semiannual 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 1,235 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 1,142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1,000 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% 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.