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Goals: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs)., Background: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings., Study: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs., Results: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in ≥12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers., Conclusions: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited. more...

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) more...

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.) more...

Goals: To determine the impact of geography and patient characteristics on hepatitis C virus (HCV) genotype and subtype distribution in a large sample of patients under routine clinical care BACKGROUND:: HCV genotype impacts disease course and response to treatment. Although several studies have reported genotype distribution within specific US populations, there are no comprehensive descriptions in large, geographically diverse cohorts., Study: Using data from the Chronic Hepatitis Cohort Study, we present the distribution of HCV genotypes (GT) and subtypes (ST) among a racially diverse cohort of over 8000 HCV-infected patients from four large US health systems., Results: Genotype distribution varied significantly by geographic and demographic factors. In age-adjusted analyses, African American patients had significantly higher prevalence of GT1 (85%) than other racial categories, largely driven by a markedly higher proportion of GT1 subtype b (∼34%) than in Asian/other (24%) and white (21%) patients. GT3 represented an increasing proportion of infections as birth decade progressed, from 4% in patients born before 1946 to 18% of those born after 1976. Within the cohort of "living/uncured" patients, highly elevated alanine aminotransferase (>2 times the upper limit of normal) was significantly more common in GT3 patients, whereas Fibrosis-4 Index scores indicative of cirrhosis were most common in the combined group of GT4&6 patients., Conclusion: Distribution of HCV genotypes and subtypes in the United States is more variable than suggested by previous national-level estimates and single-center studies. "Real-world" prevalence data may improve targeting of prevention, screening, and treatment efforts for hepatitis C. more...

Background: Limited information is available describing the uptake of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection among patients in general US health care settings. We determined the proportion of HCV-infected patients in the Chronic Hepatitis Cohort Study prescribed DAAs in 2014, who initiated treatment and identified characteristics associated with treatment initiation., Methods: Uptake was defined as the proportion of HCV-infected patients with at least 1 clinical encounter in 2013 who were prescribed a DAA regimen during 2014 and initiated the regimen by August 2015. Using multivariable analysis, we examined demographic and clinical characteristics associated with receipt of DAAs., Results: The cohort comprised 9508 patients; 544 (5.7%) started a DAA regimen. Higher annual income [adjusted odds ratios (aOR) 2.3 for income>$50K vs. <$30K], higher Fibrosis-4 score (aORs, 2.1, 2.0, and 1.4 for Fibrosis-4, >5.88, 3.25 to 5.88, 2.0 to 3.25, respectively, vs. <2.0), genotype 2 infection (aOR 2.2 vs. genotype 1), pre-2014 treatment failure (aOR 2.0 vs. treatment-naive), and human immunodeficiency virus (HIV) coinfection (aOR 1.8 vs. HCV monoinfection) were associated with DAA initiation. Black race/ethnicity (aOR 0.7 vs. whites) and Medicaid coverage (aOR 0.5 vs. private insurance) were associated with noninitiation. Sex, age, comorbidity, previous liver transplant, and duration of follow-up were not associated with receipt of DAAs., Conclusions: Among patients in these general US health care settings, uptake of DAA therapy was low in 2014, and especially so among minority and Medicaid patients. Systemic efforts to improve access to DAAs for all patients are essential to reduce morbidity and mortality from HCV infection. more...

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., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) more...

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. more...

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 (CHeCS-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)., (© 2016 John Wiley & Sons Ltd.) more...

Unlabelled: The number of persons with chronic hepatitis B virus (HBV) infection in the United States is affected by diminishing numbers of young persons who are susceptible because of universal infant vaccination since 1991, offset by numbers of HBV-infected persons migrating to the United States from endemic countries. The prevalence of HBV infection was determined by serological testing and analysis among noninstitutionalized persons age 6 years and older for: antibody to hepatitis B core antigen (anti-HBc), indicative of previous HBV infection; hepatitis B surface antigen (HBsAg), indicative of chronic (current) infection; and antibody to hepatitis B surface antigen (anti-HBs), indicative of immunity from vaccination. These prevalence estimates were analyzed in three periods of the National Health and Nutrition Examination Survey (NHANES): 1988-1994 (21,260 persons); 1999-2008 (29,828); and 2007-2012 (22,358). In 2011-2012, for the first time, non-Hispanic Asians were oversampled in NHANES. For the most recent period (2007-2012), 3.9% had anti-HBc, indicating approximately 10.8 (95% confidence interval [CI]: 9.4-12.2) million noninstitutionalized U.S. residents having ever been infected with HBV. The overall prevalence of chronic HBV infection has remained constant since 1999: 0.3% (95% CI: 0.2-0.4), and since 1999, prevalence of chronic HBV infection among non-Hispanic blacks has been 2- to 3-fold greater than the general population. An estimated 3.1% (1.8%-5.2%) of non-Hispanic Asians were chronically infected with HBV during 2011-2012, which reflects a 10-fold greater prevalence than the general population. Adjusted prevalence of vaccine-induced immunity increased 16% since 1999, and the number of persons (mainly young) with serological evidence of vaccine protection from HBV infection rose from 57.8 (95% CI: 55.4-60.1) million to 68.5 (95% CI: 65.4-71.2) million., Conclusion: Despite increasing immune protection in young persons vaccinated in infancy, an analysis of chronic hepatitis B prevalence in racial and ethnic populations indicates that during 2011-2012, there were 847,000 HBV infections (which included ~400,000 non-Hispanic Asians) in the noninstitutionalized U.S. POPULATION., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.) more...

We reviewed news reports of hepatitis A virus (HAV)-infected food handlers in the United States from 1993 to 2011 using the LexisNexis® search engine. Using U.S. news reports, we identified 192 HAV-infected food handlers who worked while infectious; of these HAV-infected individuals, 34 (18%) transmitted HAV to restaurant patrons. News reports of HAV-infected food handlers declined from 1993 to 2011. This analysis suggests that universal childhood vaccination contributed to the decrease in reports of HAV-infected food handlers, but mandatory vaccination of this group is unlikely to be cost-effective. more...

Unlabelled: Data from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) indicate that about 3.6 million people in the United States have antibodies to the hepatitis C virus, of whom 2.7 million are currently infected. NHANES, however, excludes several high-risk populations from its sampling frame, including people who are incarcerated, homeless, or hospitalized; nursing home residents; active-duty military personnel; and people living on Indian reservations. We undertook a systematic review of peer-reviewed literature and sought out unpublished presentations and data to estimate the prevalence of hepatitis C in these excluded populations and in turn improve the estimate of the number of people with hepatitis C in the United States. The available data do not support a precise result, but we estimated that 1.0 million (range 0.4 million-1.8 million) persons excluded from the NHANES sampling frame have hepatitis C virus antibody, including 500,000 incarcerated people, 220,000 homeless people, 120,000 people living on Indian reservations, and 75,000 people in hospitals. Most are men. An estimated 0.8 million (range 0.3 million-1.5 million) are currently infected. Several additional sources of underestimation, including nonresponse bias and the underrepresentation of other groups at increased risk of hepatitis C that are not excluded from the NHANES sampling frame, were not addressed in this study., Conclusion: The number of US residents who have been infected with hepatitis C is unknown but is probably at least 4.6 million (range 3.4 million-6.0 million), and of these, at least 3.5 million (range 2.5 million-4.7 million) are currently infected; additional sources of potential underestimation suggest that the true prevalence could well be higher., (© 2015 by the American Association for the Study of Liver Diseases.) more...

Background & Aims: Persons chronically infected with the hepatitis C virus (HCV) may be at higher risk for developing and dying from non-liver cancers than the general population., Methods: 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010 and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million U.S. death certificates from Multiple Cause of Death (MCOD) data. Measurements included standardized rate ratios (SRR) and relative risk (RR)., Results: The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4-52.7]), pancreas (2.5 [1.7-3.2]), rectum (2.1 [1.3-2.8]), kidney (1.7 [1.1-2.2]), non-Hodgkin lymphoma (NHL) (1.6 [1.2-2.1]), and lung (1.6 [1.3-1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1-30.1]), oral (5.2 [5.1-5.4]), rectum (2.6 [2.5-2.7]), NHL (2.3 [2.2-2.31]), and pancreatic (1.63 [1.6-1.7]) cancers. The mean ages of cancer diagnosis and cancer-related death were significantly younger among CHeCS HCV cohort patients compared to the general population for many cancers., Conclusions: Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population., (Published by Elsevier B.V.) more...

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. more...

We estimated the number of people infected with HCV in the United States who would qualify for immediate treatment according to the 2014 guidance. We based fibrosis stage on biopsy results, when available, or on FIB-4 scores. We used laboratory tests and International Classification of Diseases, Ninth Revision, Clinical Modification codes to determine if patients had any qualifying comorbidities. Of the 2.7 million people with HCV infection, we assumed that 1.35 million (50%) had been diagnosed. We estimated 457, 000 met the highest and 356, 000 the high-priority criteria for treatment, indicating that as many as 813,000 people could be treated immediately with new therapies. These estimates can inform planning efforts to address clinical capacity constraints and treatment costs. more...

Background: Previous population-based estimates in the United States have shown a relatively high prevalence of hepatitis E virus (HEV) antibody. We sought to determine whether changes in the prevalence of HEV antibody have occurred over time., Methods: We analyzed data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and NHANES III (1988-1994). Using the same serologic assay, we compared the estimated anti-HEV immunoglobulin G (IgG) prevalence and risk factors for antibody positivity for the 2 periods., Results: The prevalence of HEV antibody among those aged ≥6 years declined from 10.2% (95% confidence interval [CI], 9.1%-11.4%) during 1988-1994 to 6.0% (5.2%-6.8%) during 2009-2010, and the prevalence for those of US birth ranged from 9.6% (8.4%-10.9%) to 5.2% (4.4%-6.2%). Among US-born persons, the estimated HEV antibody prevalence declined significantly for all subgroups of age, sex, region of residence, and number of persons per room in the household; significant declines also were observed for persons at or above poverty level and for persons of non-Hispanic white, non-Hispanic black, and Mexican American race/ethnicity. No clear associations with food consumption were found., Conclusions: The anti-HEV prevalence is declining in the United States. Although the decline suggests a decrease in exposure to HEV over time, the risks associated with exposure remain unknown., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.) more...

Background: Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years)., Methods: We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions., Results: From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin., Conclusions: These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.) more...

Background: In May, 2013, an outbreak of symptomatic hepatitis A virus infections occurred in the USA. Federal, state, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. We investigated the source of the outbreak and assessed the public health measures used., Methods: We interviewed patients, obtained their shopping information, and did genetic analysis of hepatitis A virus recovered from patients' serum and stool samples. We tested products for the virus and traced supply chains., Findings: Of 165 patients identified from ten states, 69 (42%) were admitted to hospital, two developed fulminant hepatitis, and one needed a liver transplant; none died. Illness onset occurred from March 31 to Aug 12, 2013. The median age of patients was 47 years (IQR 35-58) and 91 (55%) were women. 153 patients (93%) reported consuming product B from retailer A. 40 patients (24%) had product B in their freezers, and 113 (68%) bought it according to data from retailer A. Hepatitis A virus genotype IB, uncommon in the Americas, was recovered from specimens from 117 people with hepatitis A virus illness. Pomegranate arils that were imported from Turkey--where genotype IB is common--were identified in product B. No hepatitis A virus was detected in product B., Interpretation: Imported frozen pomegranate arils were identified as the vehicle early in the investigation by combining epidemiology--with data from several sources--genetic analysis of patient samples, and product tracing. Product B was removed from store shelves, the public were warned not to eat product B, product recalls took place, and postexposure prophylaxis with both hepatitis A virus vaccine and immunoglobulin was provided. Our findings show that modern public health actions can help rapidly detect and control hepatitis A virus illness caused by imported food. Our findings show that postexposure prophylaxis can successfully prevent hepatitis A illness when a specific product is identified. Imported food products combined with waning immunity in some adult populations might make this type of intervention necessary in the future., Funding: US Centers for Disease Control and Prevention, US Food and Drug Administration, and US state and local public health departments., (Copyright © 2014 Elsevier Ltd. All rights reserved.) more...

Background: The hepatitis C virus (HCV) antibody test alone does not distinguish current from resolved infections., Aim: The study aimed to describe the percentage of current HCV infection, defined by HCV RNA positivity, among those tested positive for anti-HCV, and to examine characteristics of those with current infection., Methods: Using nationally representative data from the 2003 to 2010 National Health and Nutrition Examination Surveys, descriptive analyses and regressions were performed on data from anti-HCV-positive adults aged ≥ 40 years., Results: Of 13,909 participants examined, 304 were anti-HCV-positive. Of these, 238 or 75.3% [95% confidence interval (CI) 67.5-81.8%] had detectable viral RNA. The percentage of current, unresolved HCV infection was highest among non-Hispanic Blacks (91.1%) and lowest among those with a college education (57.3%). In multivariate analyses, non-Hispanic Blacks were more likely to have current HCV infection compared to non-Hispanic Whites (adjusted odds ratio 3.9, 95% CI 1.6-9.2). Among persons with current HCV infection, most had elevated alanine aminotransferase (56.5%) or aspartate aminotransferase (71.8%) levels, but only 35.3% reported having been diagnosed with any abnormal liver conditions. Excessive alcohol drinking was reported by 27.3% of participants with current HCV infection., Conclusions: Among adults aged ≥ 40 years who had ever been infected with HCV, approximately three-quarters had current, unresolved HCV infection. Non-Hispanic Blacks were more likely to have current infection than non-Hispanic Whites. The majority of those with current infection had abnormal liver function tests but had not received appropriate diagnoses. Many currently infected persons would benefit from lifestyle modifications to avoid the multiplicative effect of alcohol on HCV infection. more...

Background & Aims: Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers., Methods: We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence., Results: Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL., Conclusions: In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.) more...

Background: The number of deaths in hepatitis C virus (HCV)-infected persons recorded on US death certificates has been increasing, but actual rates and causes of death in these individuals have not been well elucidated., Methods: Disease-specific, liver-related, and non-liver-related mortality data for HCV-infected patients in an observational cohort study, the Chronic Hepatitis Cohort Study (CHeCS) at 4 US healthcare systems, were compared with multiple cause of death (MCOD) data in 12 million death certificates in 2006-2010. Premortem diagnoses, liver biopsies, and FIB-4 scores (a noninvasive measure of liver damage) were examined., Results: Of 2 143 369 adult patients seen at CHeCS sites in 2006-2010, 11 703 (0.5%) had diagnosed chronic HCV infection, and 1590 (14%) died. The majority of CHeCS decedents were born from 1945 to 1965 (75%), white (50%), and male (68%); mean age of death was 59 years, 15 years younger than MCOD deaths. The age-adjusted mortality rate for liver disease in CHeCS was 12 times higher than the MCOD rate. Before death, 63% of decedents had medical record evidence of chronic liver disease, 76% had elevated FIB-4 scores, and, among those biopsied, 70% had moderate or worse liver fibrosis. However, only 19% of all CHeCS decedents and only 30% of those with recorded liver disease had HCV listed on their death certificates., Conclusions: HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease. more...

Objectives: Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers., Methods: We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011., Results: For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case)., Conclusions: These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. more...

Background: Previous research indicates that the mortality burden from viral hepatitis is growing, particularly among middle-aged persons. To monitor progress toward prevention goals, it is important to continue to document characteristics and comortalities of these deaths. This study sought to examine demographic characteristics and the most frequent causes of death among decedents with a viral hepatitis-related death., Methods: A cross-sectional study was performed on approximately 2.4 million death records from 2010. We calculated mortality rates for decedents with and without hepatitis A, B, and C virus (HAV, HBV, and HCV) and relative risks for the most frequently cited conditions in decedents with and without HBV and HCV., Results: In 2010, there were 18 473 (0.7%) deaths with HAV, HBV, and HCV listed among causes of death, disproportionately in those aged 45-64 years. Among the 10 frequent causes of death, decedents listing HBV or HCV died, on average, 22-23 years earlier than decedents not listing these infections. HBV- and HCV-infected decedents aged 45-64 years had an increased risk of having the following conditions reported than decedents without these infections: cancer of liver and intrahepatic bile duct; fibrosis, cirrhosis, and other liver diseases; alcohol-related liver disease; gastrointestinal hemorrhage; human immunodeficiency infection; acute and unspecified renal failure; and septicemia (HCV only)., Conclusions: Decedents with other causes of death that include HBV or HCV died 22-23 years earlier than decedents not listing these infections. These data suggest and support the need for prevention, early identification, and treatment of HBV and HCV. more...

Unlabelled: Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B., Conclusion: These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care., (Copyright © 2013 American Association for the Study of Liver Diseases.) more...

Objectives: Centers for Disease Control and Prevention has recommended a 1-time HCV test for persons born from 1945 through 1965 to supplement current risk-based screening. We examined indications for testing by birth cohort (before 1945, 1945-1965, and after 1965) among persons with past or current HCV., Methods: Cases had positive HCV laboratory markers reported by 4 surveillance sites (Colorado, Connecticut, Minnesota, and New York) to health departments from 2004 to 2010. Health department staff abstracted demographics and indications for testing from cases' medical records and compiled this information into a surveillance database., Results: Of 110, 223 cases of past or current HCV infection reported during 2004-2010, 74, 578 (68%) were among persons born during 1945-1965. Testing indications were abstracted for 45, 034 (41%) cases; of these, 29 ,544 (66%) identified at least 1 Centers for Disease Control and Prevention-recommended risk factor as a testing indication. Overall, 74% of reported cases were born from 1945 to 1965 or had an injection drug use history., Conclusions: These data support augmenting the current HCV risk-based screening recommendations by screening adults born from 1945 to 1965. more...

Background: Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease., Methods: Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale., Results: We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher., Conclusions: In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies. more...

Objectives: We estimated rates and determinants of hepatitis C virus (HCV) testing, infection, and linkage to care among US racial/ethnic minorities., Methods: We analyzed the Racial and Ethnic Approaches to Community Health Across the US Risk Factor Survey conducted in 2009-2010 (n = 53,896 minority adults)., Results: Overall, 19% of respondents were tested for HCV. Only 60% of those reporting a risk factor were tested, with much lower rates among Asians reporting injection drug use (40%). Odds of HCV testing decreased with age and increased with higher education. Of those tested, 8.3% reported HCV infection. Respondents with income of $75,000 or more were less likely to report HCV infection than those with income less than $25,000. College-educated non-Hispanic Blacks and Asians had lower odds of HCV infection than those who did not finish high school. Of those infected, 44.4% were currently being followed by a physician, and 41.9% had taken HCV medications., Conclusions: HCV testing and linkage to care among racial/ethnic minorities are suboptimal, particularly among those reporting HCV risk factors. Socioeconomic factors were significant determinants of HCV testing, infection, and access to care. Future HCV testing and prevention activities should be directed toward racial/ethnic minorities, particularly those of low socioeconomic status. more...

Introduction: Compliance with National Cholesterol Education Program Adult Treatment Panel III (NCEP) guidelines has been shown to significantly reduce incident cardiovascular events. We investigated physicians' compliance with NCEP guidelines to reduce cardiovascular disease (CVD) risk in a population infected with HIV., Methods: We analyzed HIV Outpatient Study (HOPS) data, following eligible patients from January 1, 2002, or first HOPS visit thereafter to calculate 10-year cardiovascular risk (10yCVR), until September 30, 2009, death, or last office visit. We categorized participants into four 10yCVR strata, according to guidelines determined by NCEP, the Infectious Disease Society of America, and the Adult AIDS Clinical Trials Group. We calculated percentages of patients treated for dyslipidemia and hypertension, calculated percentages of patients who achieved recommended goals, and categorized them by 10yCVR stratum., Results: Of 2,005 patients analyzed, 33.7% had fewer than 2 CVD risk factors. For patients who had 2 or more risk factors, 10yCVR was less than 10% for 28.2%, 10% to 20% for 18.2%, and higher than 20% for 20.0% of patients. Of patients eligible for treatment, 81% to 87% were treated for elevated low-density lipoprotein cholesterol/non-high-density lipoprotein cholesterol (LDL-C/non-HDL-C), 2% to 11% were treated for low HDL-C, 56% to 91% were treated for high triglycerides, and 46% to 69% were treated for hypertension. Patients in higher 10yCVR categories were less likely to meet treatment goals than patients in lower 10yCVR categories., Conclusion: At least one-fifth of contemporary HOPS patients have a 10yCVR higher than 20%, yet a large percentage of at-risk patients who were eligible for pharmacologic treatment did not receive recommended interventions and did not reach recommended treatment goals. Opportunities exist for CVD prevention in the HIV-infected population. more...

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. more...

The impact of hepatitis C virus (HCV) infection on health and medical care in the United States is a major problem for infectious disease physicians. Although the incidence of HCV infection has declined markedly in the past 2 decades, chronic infection in 3 million or more residents now accounts for more disease and death in the United States than does human immunodeficiency virus (HIV)/AIDS. Current trends in the epidemiology of HCV infection include an apparent increase in young, often suburban heroin injection drug users who initiate use with oral prescription opioid drugs; infections in nonhospital healthcare (clinic) settings; and sexual transmission among HIV-infected persons. Infectious disease physicians will increasingly have the responsibility of diagnosing and treating HCV patients. An understanding of how these patients were infected is important for determining whom to screen and treat. more...

Background: The increasing health burden and mortality from hepatitis B virus (HBV) and hepatitis C virus (HCV) in the United States are underappreciated., Objective: To examine mortality from HBV; HCV; and, for comparison, HIV., Design: Analysis of U.S. multiple-cause mortality data from 1999 to 2007 from the National Center for Health Statistics., Setting: All U.S. states and the District of Columbia., Participants: Approximately 22 million decedents., Measurements: Age-adjusted mortality rates from HBV, HCV, and HIV. Logistic regression analyses of 2007 data generated 4 independent models per outcome (HCV- or HBV-related deaths) that each included 1 of 4 comorbid conditions and all sociodemographic characteristics., Results: Between 1999 and 2007, recorded deaths from HCV [corrected] increased significantly to 15,106, whereas deaths from HIV declined to 12,734 by 2007. Factors associated with HCV-related deaths included chronic liver disease, HBV co-infection, alcohol-related conditions, minority status, and HIV co-infection. Factors that increased odds of HBV-related death included chronic liver disease, HCV co-infection, Asian or Pacific Islander descent, HIV co-infection, and alcohol-related conditions. Most deaths from HBV and HCV occurred in middle-aged persons., Limitation: A person other than the primary physician of the decedent frequently completed the death certificate, and HCV and HBV often were not detected and thus not reported as causes of death., Conclusion: By 2007, HCV had superseded HIV as a cause of death in the United States, and deaths from HCV and HBV disproportionately occurred in middle-aged persons. To achieve decreases in mortality similar to those seen with HIV requires new policy initiatives to detect patients with chronic hepatitis and link them to care and treatment., Primary Funding Source: Centers for Disease Control and Prevention. more...

Background: Knowledge of the genotypic distribution of hepatitis B virus (HBV) facilitates epidemiologic tracking and surveillance of HBV infection as well as prediction of its disease burden. In the United States, HBV genotyping studies have been conducted for chronic but not acute hepatitis B., Methods: Serum samples were collected from patients with acute hepatitis B cases reported from the 6 counties that participated in the Sentinel Counties Study of Acute Viral Hepatitis from 1999 through 2005. Polymerase chain reaction followed by nucleotide sequencing of a 435-base pair segment of the HBV S gene was performed, and the sequences were phylogenetically analyzed., Results: Of 614 patients identified with available serum samples, 75% were infected with genotype A HBV and 18% were infected with genotype D HBV. Thirty-two percent of genotype A sequences constituted a single subgenotype A2 cluster. The odds of infection with genotype A (vs with genotype D) were 5 times greater among black individuals than among Hispanic individuals (odds ratio [OR], 5; 95% confidence interval [CI], 2.3-10.7). The odds of infection with genotype A were 49, 8, and 4 times greater among patients from Jefferson County (Alabama), Pinellas County (Florida), and San Francisco (California), respectively, than among those living in Denver County (Colorado). Genotype A was less common among recent injection drug users than it was among non-injection drug users (OR, 0.2; 95% CI, 0.1-0.4)., Conclusions: HBV genotype distribution was significantly associated with ethnicity, place of residence, and risk behavior. more...

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of end-stage liver disease, including cirrhosis, liver failure and primary liver cancer. There are now seven antiviral agents approved by the United States Food and Drug Administration (FDA) for the management of chronic HBV infection. Despite the fact that there are between 1.4 and 2 million chronic HBV infections in the United States, fewer than 50,000 people per year receive prescriptions for HBV antiviral medications. This report discusses possible explanations for the disparity between the number of people who are chronically infected and the number of people who receive treatment. Explanations for this incongruence include the potentially large number of infected persons who are unscreened and thus remain undiagnosed, and lack of access, including insurance, education and referral to appropriate medical care, particularly for disproportionately infected populations., (© 2010 Blackwell Publishing Ltd.) more...

Background: Traditional cardiovascular disease (CVD) risk factors, human immunodeficiency virus (HIV) infection, and antiretroviral (ARV) agents have been associated with CVD events in HIV-infected patients. We investigated the association of low CD4(+) T lymphocyte cell count with incident CVD in a cohort of outpatients treated in 10 HIV specialty clinics in the United States., Methods: We studied patients who were under observation from 1 January 2002 (baseline), categorized them according to National Cholesterol Education Program guidelines into 10-year cardiovascular risk score (10-y CVR) groups , and observed them until CVD event, death, last HIV Outpatient Study contact, or 30 September 2009. We calculated rates of incident CVD events and identified associated baseline risk factors using Cox proportional hazard models. We also performed a nested case-control study to examine the association of latest CD4(+) cell count with CVD events., Results: Among 2005 patients, 148 experienced incident CVD events. CVD incidence increased steadily from 0.4 to 3.0 events per 100 person-years from lowest to highest 10-y CVR group (P < .001). In multivariable Cox analyses adjusted for 10-y CVR, CD4(+) cell count <350 cells/mm(3) was associated with incident CVD events (hazard ratio, 1.58 [95% confidence interval, 1.09-2.30], compared with >500 cells/mm(3)), suggesting an attributable risk of approximately 20%. In the multivariable case-control analyses, traditional CVD risk factors and latest CD4(+) cell count <500 cells/mm(3), but not cumulative use of ARV class or individual drugs, were associated with higher odds of experiencing CVD events., Conclusion: CD4(+) count <500 cells/mm(3) is an independent risk factor for incident CVD, comparable in attributable risk to several traditional CVD risk factors in the HIV Outpatient Study cohort. more...

The term "molecular epidemiology" has been ascribed to a host of different activities that involve gene-sequence analysis. Some examples of molecular epidemiology include modeling exercises of phylogenetic trees to reconstruct epidemics; studies of the evolution of hepatitis C virus (HCV); rates of nucleotide substitution in the hepatitis B virus (HBV) surface (S) gene; variations in the core promoter/pre-core/core region of HBV genotype C from different sources; analysis of HBV surface antigen mutations; molecular clock analyses of the short-term evolution of HCV; and analyses of clades and surface antigen polymorphisms of HBV. However, for most epidemiologists molecular epidemiology of viral hepatitis usually refers to studies of gene-sequence homology in HBV or HCV recovered from people in the community or an institution that allows better characterization and assignment of related clusters of infection. more...

Treatment of human immunodeficiency virus (HIV) infection with highly active combination antiretroviral therapy has increased survival and shifted the spectrum of HIV-associated morbidity and mortality from opportunistic infections toward a variety of other medical conditions. The prospective cohort Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) monitors the clinical course of HIV-infected individuals treated with combination antiretroviral therapy in 4 US cities. Every 6 months, clinical assessments, medical record abstraction, audio computer-assisted self-interview, and neurocognitive measurements are completed and blood and urine specimens are banked centrally. At enrollment and periodically thereafter, additional techniques such as anal cytology, dual energy x-ray absorptiometry, carotid ultrasonography, echocardiography, and abdominal and cardiac computed tomography are performed. From March 2004 through June 2006, 700 participants were enrolled; median age was 41 years, 76% were men, 58% were non-Hispanic white, 62% were men who have sex with men, 78% were taking combination antiretroviral therapy (of whom 86% had an HIV viral load of <400 copies/mL), and median CD4+ T-lymphocyte count was 459 cells/mm(3) (interquartile range: 324-660). The SUN Study provides a wealth of data that will inform and improve the clinical management of HIV-infected individuals in the modern era. more...

In the United States, transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) from health care exposures has been considered uncommon. However, a review of outbreak information revealed 33 outbreaks in nonhospital health care settings in the past decade: 12 in outpatient clinics, 6 in hemodialysis centers, and 15 in long-term care facilities, resulting in 448 persons acquiring HBV or HCV infection. In each setting, the putative mechanism of infection was patient-to-patient transmission through failure of health care personnel to adhere to fundamental principles of infection control and aseptic technique (for example, reuse of syringes or lancing devices). Difficult to detect and investigate, these recognized outbreaks indicate a wider and growing problem as health care is increasingly provided in outpatient settings in which infection control training and oversight may be inadequate. A comprehensive approach involving better viral hepatitis surveillance and case investigation, health care provider education and training, professional oversight, licensing, and public awareness is needed to ensure that patients are always afforded basic levels of protection against viral hepatitis transmission. more...

Objectives: To assess temporal trends in the rates of hospitalizations and associated diagnoses among HIV-infected patients before and during the era of highly active antiretroviral therapy., Design: A prospective cohort study of 7155 patients enrolled in the HIV Outpatient Study at 10 US HIV clinics., Methods: We evaluated rates of hospitalizations for major categories of medical conditions during 1994-2005 and modeled trends in these rates using multivariable Poisson regression models for repeated observations. We assessed patient characteristics associated with hospitalization using multiple logistic regression., Results: The rates of hospitalizations (per 100 person-years) fell from 24.6 in 1994 to 11.8 in 2005 (P < 0.0001). The rates of hospitalizations for AIDS opportunistic infections decreased from 7.6 in 1994-1996 to 1.0 in 2003-2005 (P < 0.0001). AIDS opportunistic infections were present at 31% of hospitalizations in 1994-1996 versus 9.5% in 2003-2005, and chronic end-organ disease conditions were present at 7.2% of such hospitalizations in 1994-1996 versus 14.3% in 2003-2005. Mean CD4+ cell count at hospitalization increased from 115 cells/mul in 1994 to 310 cells/mul in 2005. Factors independently associated with hospitalization in the highly active antiretroviral therapy era (1997-2005) included older age, history of substance abuse, lower CD4+ cell count, history of AIDS, and public health insurance., Conclusion: The rates of hospitalizations for HIV-infected patients declined substantially during 1994-2005, due mainly to reductions in the AIDS opportunistic infections. Compared with the period 1994-1997, patients in the highly active antiretroviral therapy era were hospitalized with higher CD4+ cell counts and more frequently for chronic end-organ conditions. more...

Background: Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population., Objective: To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003., Design: Prospective observational cohort studies., Setting: United States., Patients: 54,780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47,832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157,819 person-years of follow-up from 1992 to 2003, and 334,802,121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries., Measurements: Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population., Results: The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time., Limitations: Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated., Conclusion: The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003. more...

Objectives: Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS)., Methods: We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values., Results: The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11)., Conclusions: The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia. more...

This review assesses differences and similarities of the states in planning for pandemic influenza. We reviewed the recently posted plans of 49 states for vaccination, early epidemic surveillance and detection, and intraepidemic plans for containment of pandemic influenza. All states generally follow vaccination priorities set by the Advisory Committee on Immunization Practices. They all also depend on National Sentinel Physician Surveillance and other passive surveillance systems to alert them to incipient epidemic influenza, but these systems may not detect local epidemics until they are well established. Because of a lack of epidemiologic data, few states explicitly discuss implementing nonpharmaceutical community interventions: voluntary self-isolation (17 states [35%]), school or other institutional closing (18 [37%]), institutional or household quarantine (15 [31%]), or contact vaccination or chemoprophylaxis (12 [25%]). This review indicates the need for central planning for pandemic influenza and for epidemiologic studies regarding containment strategies in the community. more...

This study assessed whether behavioral differences explained higher human immunodeficiency virus (HIV) seroprevalence among injection drug users (IDUs) in three East Coast versus two West Coast cities in the United States. Sociodemographic, sexual, and injecting information were collected during semiannual face-to-face interviews. Baseline data from New York City; Baltimore, Maryland; and New Haven, Connecticut, were compared with data from Los Angeles, California, and San Jose, California. Among 1,528 East Coast and 1,149 West Coast participants, HIV sero-prevalence was 21.5% and 2.3%, respectively (odds ratio [OR] 11.9; 95% confidence interval [CI] 7.9-17.8). HIV risk behaviors were common among IDUs on both coasts, and several were more common among West Coast participants. Adjusting for potential risk factors, East (vs. West) Coast of residence remained highly associated with HIV status (adjusted OR 12.14; 95% CI 7.36-20.00). Differences in HIV sero-prevalence between East and West Coast cities did not reflect self-reported injection or sexual risk behavior differences. This suggests that other factors must be considered, such as the probability of having HIV-infected injection or sexual partners. Prevention efforts are needed on the West Coast to decrease HIV-associated risk behaviors among IDUs, and further efforts are also needed to reduce HIV incidence on the East Coast. more...

HIV/AIDS-associated and non-HIV/AIDS-associated death rates and causes of death between 1993 and 1999 were examined in 885 HIV-infected women and 425 uninfected women of the HIV Epidemiology Research Study cohort. Causes of death were determined by review of death certificates and the National Death Index. Adjusted hazard ratios were calculated for mortality risk factors. In the 885 HIV-infected women and 425 uninfected women, 234 deaths and 8 deaths, respectively, occurred by December 31, 1999. All-cause death rates in the HIV-infected women were unchanged between the pre-HAART (1993-1996) and HAART eras (1997-1999)-5.1 versus 5.4 deaths per 100 person-years (py). AIDS as a cause of death decreased from 58% of all deaths in 1996 to 19% in 1999, while HAART use increased to 42% by the end of 1999. In spite of the modest proportion ever using HAART, HIV-related mortality rates did decline, particularly in women with CD4+ cell counts less than 200/mm(3). Drug-related factors were prominent: for the 129 non-AIDS-defining deaths, hepatitis C positivity (relative hazard [RH] 2.6, P <.001) and injection drug use (RH 1.7, P = 0.02) were strong predictors of mortality, but were not significant in the Cox model for 105 AIDS-defining deaths (RH 0.9, P >.30 and RH 0.7, P >.30, respectively. The regression analysis findings, along with the high percentage of non-AIDS deaths attributable to illicit drug use, suggest that high levels of drug use in this population offset improvements in mortality from declining numbers of deaths due to AIDS. more...

Background: The rates and risk factors for overall and medical condition-specific hospitalizations in HIV-positive women have not been examined in detail or compared with rates in risk factor-matched HIV-negative women., Objective: To determine the rates and risk factors for overall and condition-specific hospitalizations., Methods: Prospective cohort study of 885 HIV-positive women and 425 HIV-negative women followed for semiannual research visits between 1993 and 2000 in 4 urban locations in the United States. Outcome measures were hospitalization diagnoses with diabetes mellitus, nonacute renal conditions, cardiovascular conditions, liver conditions, AIDS defining conditions, and overall hospitalizations. Clinical and laboratory risk factors were assessed at research visits every 6 months, and effects of risk factors on hospitalization rates were calculated using generalized estimating equations and Poisson regression., Results: Renal laboratory abnormalities, hypertension, and clinical AIDS were each associated with 3 of the 5 condition-specific hospitalization rates. Over time, diabetes-, nonacute renal-, and cardiovascular-related rates were flat or slightly increased and liver-related rates were significantly increased in HIV-positive women. Hospitalization rates with an AIDS-defining condition declined sharply in the latter half of the study period., Conclusions: In this population of largely African-American, inner-city, HIV-infected women, renal abnormalities, hypertension, and hepatitis C virus infection were common. Rate ratios indicated that "non-AIDS" risk factors were important predictors of hospitalization. In the highly active antiretroviral therapy era, clinicians must pay attention to these risk factors for morbidity and should closely monitor renal abnormalities, hypertension, and hepatitis status. more...

Background: Data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited., Objective: To determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women., Design: The incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women., Setting: Women from the general community or HIV care clinics in four urban locations in the United States., Outcome Measures: Creatinine of >or=1.4 mg/dL, proteinuria 2 or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%)., Results: At baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9-3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2.7%), p<.0001) in HIV-infected women with, compared with those without these renal abnormalities., Conclusions: Proteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons. more...

Objectives: To evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care., Design: Cross-sectional analysis of the 1998 interview from the HIV Epidemiology Research Study (HERS) cohort., Methods: Data from 273 HIV-infected women in the HERS were analyzed by multiple logistic regression to calculate predictors of the use of HIV specialist care providers. Variables included study site, age, education, insurance status, income, substance abuse, depression, AIDS diagnosis, CD4 + lymphocyte count, and HIV-1 viral load. In addition, medical indications for therapy and medical advice to begin antiretroviral therapy were assessed., Results: Of 273 women, 222 (81%) used HIV specialists and 51 (19%) did not. Having health insurance, not being an injection drug user, and being depressed were predictive of using HIV specialist care (all p < or = .05). Although medical indications for therapy in the two groups were comparable, the rate of highly active antiretroviral therapy (HAART) use was significantly higher in women using HIV specialist care (27%) compared with those not using HIV specialists (7.8%). Women using HIV specialists received significantly more advice to begin antiretroviral therapy (ART) in the 6 months prior to the interview compared with those not using specialists (relative risk, 2.4; 95% CI = 1.3-4.6)., Conclusions: Having insurance, not being an injection drug user, and being depressed all increased the likelihood of women receiving HIV specialty care, which, in turn, increased the likelihood of receiving recommended therapies. The level of HAART use (23%) and any ART use (47%) in these HIV-infected women was disturbingly low. Despite comparable medical indications, fewer women obtaining care from other than HIV specialists received HAART. These data indicate substantial gaps in access to HIV specialist care and thereby to currently recommended antiretroviral treatment. more...