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

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

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

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

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

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

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

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

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

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

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

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

Background. Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes. Methods. US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined. Results. Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17-73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P = .08) and took a greater number of other medications (median number of medications, 4 vs. 2; P = .05) than did those who recovered, but these 2 factors were correlated (P<.01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died. Conclusions. RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury. [ABSTRACT FROM AUTHOR]

The article summarizes recommendations of the Advisory Committee on Immunization Practices (ACIP) on hepatitis B vaccination far adults with diabetes mellitus. It cites the severity of acute hepatitis B virus (HBV) infection among adults. Hepatitis B vaccines that are available in the U.S. are mentioned. Recommendations of the ACIP include the administration of hepatitis B vaccination to unvaccinated adults with diabetes mellitus who are aged 19-25 years old.

Background Trends in the epidemiology of chronic hepatitis B (CHB) among routine clinical care patients in the United States are not well documented. We used data from the Chronic Hepatitis Cohort Study to investigate changes in prevalence and newly recorded cases of CHB from 2006 to 2015. Methods Annual percentage changes (APCs) were estimated using join point Poisson regression. Analyses were adjusted by study site; when an interaction with the trend was observed, APCs were estimated by subgroups. Differences in rates based on race, age, and sex were calculated with rate ratios. Results We identified 5492 patients with CHB within select health systems with total populations that ranged from 1.9 to 2.4 million persons. From 2006 to 2014, the prevalence of diagnosed CHB increased from 181.3 to 253.0 per 100 000 persons in the health system population; from 2014 to 2015, it declined to 237.0 per 100 000 persons. APC was +3.7%/y through 131 December 2014 (P <.001) and −15.0%/y (P <.001) thereafter. The rate of newly reported cases of CHB did not change significantly across the study period (APC, −1.1%/y; P =.07). The rates of newly reported cases were 20.5 times higher among patients in the Asian American/American Indian/Pacific Islander (ASINPI) category, compared with white patients, and 2.8 times higher among African American patients. The ratio of male to female patients was roughly 3:2. Conclusions The prevalence of diagnosed CHB in this US patient population increased from 2006 to 2014, after which it decreased significantly. Rates declined most rapidly among patients ≤40 or 61–70 years old, as well as among ASINPI patients. The rate of newly reported cases remained steady over the study period. [ABSTRACT FROM AUTHOR]

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

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

Hepatitis A is a vaccine-preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person-to-person transmission have been widespread in the United States since 2016. We used public-use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A-listed deaths during non-outbreak (2011-2015) and outbreak (2017-2021) periods and assessed the median age at death among decedents with and without hepatitis A-listed deaths during the outbreak period. From the non-outbreak period to the outbreak period, hepatitis A-listed deaths more than doubled (from 369 to 801), while the hepatitis A-listed age-adjusted mortality rate increased 150% (p < 0.001). When compared with the non-outbreak period, hepatitis A-listed decedents during the outbreak period were more frequently male, aged 18-49 years, non-Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A-listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non-outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A-listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017-2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Importance: US hepatitis B mortality has been described nationally, but examination subnationally may identify differences in mortality rates and decedent characteristics, including birthplace., Objective: To examine characteristics of decedents with hepatitis B-listed deaths during 2010 to 2019 and compare age-adjusted hepatitis B-listed death rates during 2010 to 2019 vs 2000 to 2009., Design, Setting, and Participants: This cross-sectional study used Multiple Cause of Death data from 50 US states and the District of Columbia (DC) from 2000 to 2019 to assess characteristics of US residents with hepatitis B listed as an underlying cause of death (UCOD) or contributing cause of death on death certificates. Data were analyzed from September 2019 to May 2022., Exposures: Hepatitis B listed as underlying or contributing cause of death., Main Outcomes and Measures: Outcomes of interest were hepatitis B-listed death counts, age-adjusted rates, and characteristics of decedents during 2000 to 2019. The distribution of hepatitis B-listed deaths according to sociodemographic characteristics and UCOD among US- and non-US-born decedents were also examined., Results: A total of 35 280 decedents with hepatitis B listed as the cause of death were identified, including 17 483 deaths during 2010 to 2019. Decedents were 63.3% US-born, and 25.8% of decedents were Asian or Pacific Islander and 46.5% of decedents were White; 28.4% of decedents were listed as having hepatitis C virus (HCV) or HIV coinfection. State-level rates significantly surpassed the overall US rate (0.47 deaths per 100 000 population) in DC (high, 1.78 deaths per 100 000 population), Hawaii, Oklahoma, California, Tennessee, West Virginia, Mississippi, Oregon, Washington, Louisiana, Kentucky, and New York (low, 0.61 deaths per 100 000 population). Median (IQR) age at hepatitis B death was significantly younger in Kentucky (54.0 [46.0-64.0] years), West Virginia (56.0 [47.0-65.0] years), Tennessee (57.0 [50.0-65.0] years), Mississippi (58.0 [50.0-65.0] years), and Ohio (59.0 [50.0-66.0] years) than the national median (60.0 [53.0-69.0] years), which itself was significantly younger than nonhepatitis B-listed deaths (77 [63.0-87.0] years; P < .001). Hepatitis B was the UCOD among approximately 30% of US- and non-US-born decedents with hepatitis B COD. Irrespective of birthplace, most decedents had liver-related UCOD. Compared with non-US-born decedents, US-born decedents more frequently had nonliver conditions listed as UCOD. Liver cancer was the predominant UCOD among non-US-born decedents (37.9% of decedents). From 2000 to 2009 compared with 2010 to 2019, the hepatitis B-listed mortality rate significantly decreased nationally (change, -18.97%) and in 14 states; significant increases were observed in West Virginia (change, 83.78%) and Kentucky (change, 69.44%)., Conclusions and Relevance: These findings suggest that US-born decedents constituted two-thirds of all hepatitis B-listed deaths and median age at death was youngest in Appalachian states. Irrespective of birthplace, most decedents had liver-related UCOD; however, US-born decedents more frequently had nonliver UCOD than non-US-born decedents. In addition to addressing liver-related complications, US-born persons with chronic infection may also require diagnosis and management of multiple comorbidities.

Background and Aims: During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A., Approach and Results: To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (P < 0.05) higher odds of mortality were associated with preexisting nonviral liver disease (adjusted odds ratio [aOR], 5.2), history of hepatitis B (aOR, 2.4), diabetes (aOR, 2.2), and cardiovascular disease (aOR, 2.2), as well as initial Model for End-Stage Liver Disease (MELD) score ≥ 30 (aOR, 10.0), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2 (aOR, 10.3), and platelet count < 150,000/μL (aOR, 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex)., Conclusions: Preexisting liver disease, diabetes, cardiovascular disease, and initial MELD score ≥ 30, AST/ALT ratio ≥ 1, and platelet count < 150,000/μL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the recommendation of the Advisory Committee on Immunization Practices to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered., (© 2020 by the American Association for the Study of Liver Diseases.)

Background: Since 2016, the United States has experienced person-to-person hepatitis A outbreaks unprecedented in the vaccine era. The proportion of cases hospitalized in these outbreaks exceeds historical national surveillance data., Methods: We described the epidemiology, characterized the reported increased morbidity, and identified factors associated with hospitalization during the outbreaks by reviewing a 10% random sample of outbreak-associated hepatitis A cases in Kentucky, Michigan, and West Virginia-3 heavily affected states. We calculated descriptive statistics and conducted age-adjusted log-binomial regression analyses to identify factors associated with hospitalization., Results: Participants in the random sample (n = 817) were primarily male (62.5%) with mean age of 39.0 years; 51.8% were hospitalized. Among those with available information, 73.2% reported drug use, 14.0% were experiencing homelessness, 29.7% were currently or recently incarcerated, and 61.6% were epidemiologically linked to a known outbreak-associated case. Residence in Michigan (adjusted risk ratio [aRR] = 1.8), being a man who has sex with men (aRR = 1.5), noninjection drug use (aRR = 1.3), and homelessness (aRR = 1.3) were significantly (P < .05) associated with hepatitis A-related hospitalization., Conclusions: Our findings support current Advisory Committee on Immunization Practices recommendations to vaccinate all persons who use drugs, men who have sex with men, and persons experiencing homelessness against hepatitis A., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

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.

There are limited data examining the relationship between psychosocial factors and receipt of direct-acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health-related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017-2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow-up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life-related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow-up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion: In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C-related morbidity and mortality., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The United States is in the midst of unprecedented person-to-person hepatitis A outbreaks. By using Healthcare Cost and Utilization Project data, we estimated the average costs per hepatitis A-related hospitalization in 2017. These estimates can guide investment in outbreak prevention efforts to stop the spread of this vaccine-preventable disease.

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.)

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.

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.

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.)

Background & Aims: Most regions of the world have ≤3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where five HBV genotypes (A, B, C, D, F) have been identified., Methods: Our cohort comprised AN persons with chronic HBV infection identified during 1983-2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semi-annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status., Results: Among the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person-years of follow-up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.14-13.74], C (aOR: 16.3, 95% CI: 5.20-51.11) and F (aOR: 13.9, 95% CI: 5.30-36.69)., Conclusion: HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D., Competing Interests: None of the authors have any relevant conflicts of interest to disclose., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

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.)

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.

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.)

Little is known about the characteristics of acute viral hepatitis cases in the United States (US)-Mexico border region. We analyzed characteristics of acute viral hepatitis cases collected from the Border Infectious Disease Surveillance Project from January 2000-December 2009. Over the study period, 1,437 acute hepatitis A, 311 acute hepatitis B, and 362 acute hepatitis C cases were reported from 5 Mexico and 2 US sites. Mexican hepatitis A cases most frequently reported close personal contact with a known case, whereas, US cases most often reported cross-border travel. Injection drug use was common among Mexican and US acute hepatitis B and C cases. Cross-border travel during the incubation period was common among acute viral hepatitis cases in both countries. Assiduous adherence to vaccination and prevention guidelines in the US is needed and strategic implementation of hepatitis vaccination and prevention programs south of the border should be considered.

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.