Eyasu H. Teshale

The Two Faces of Hepatitis E Virus

Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%-21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration-approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world.

Baseline Characteristics and Mortality Among People in Care for Chronic Viral Hepatitis: The Chronic Hepatitis Cohort Study

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

Evidence of Person-to-Person Transmission of Hepatitis E Virus during a Large Outbreak in Northern Uganda

BACKGROUND Outbreaks of infection with hepatitis E virus (HEV) are frequently attributed to contaminated drinking water, even if direct evidence for this is lacking. METHODS We conducted several epidemiologic investigations during a large HEV infection outbreak in Uganda. RESULTS Of 10,535 residents, 3218 had HEV infection; of these, 2531 lived in households with >1 case. HEV was not detected in drinking water or zoonotic sources. Twenty-five percent of cases occurred > or = 8 weeks after onset of hepatitis in an index case in the household. Households with > or = 2 cases were more likely to have a member(s) who attended a funeral, had close contact with a jaundiced person, or washed hands in a common basin with others (P < .05 for all). CONCLUSIONS A high attack rate in households, lack of a common source of infection, and poor hygienic practices in households with > or = 2 cases suggest person-to-person transmission of HEV during this outbreak.

Hepatitis E Epidemic, Uganda

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

Antiviral Therapy for Chronic Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma in a US Population

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.

Problematic use of prescription-type opioids prior to heroin use among young heroin injectors

Background Misuse of prescription-type opioids and related adverse health effects are increasing, but little is known about the role of these drugs as a precursor to heroin use. We conducted an exploratory study to determine the proportion of young heroin injectors reporting problematic use of prescription-type opioids prior to using heroin, and to describe the factors associated with prior problematic prescription-type opioid use. Methods Between March 2009 and June 2010, we recruited injection drug users (IDUs) for a cross-sectional study of hepatitis C virus infection risk. Participants were aged 18–40 years and had injected illicit drugs within the previous six months. A computerized self-administered survey assessed sociodemographics, drug use history, human immunodeficiency virus (HIV)/hepatitis C virus risk behaviors and perceptions, and medical history. We added questions on prescription-type opioid use to the parent study in March 2010; heroin injectors who subsequently enrolled and reported problematic prescription-type opioid use prior to heroin initiation were compared with other heroin IDUs using univariate and multivariate regression methods. Results Among 123 heroin IDUs, 49 (39.8%) reported problematic prescription-type opioid use prior to heroin initiation (“prescription-type opioid first injection drug users” [PTO-First IDUs]). PTO-First IDUs had higher odds of injecting with friends (adjusted odds ratio [AOR] 6.01; 95% confidence interval [CI] 1.90–19.07), getting new syringes from a spouse/family member/sex partner (AOR 23.0; 95% CI 2.33–226.0), knowing about the local syringe exchange program (AOR 7.28; 95% CI 1.17–45.05), using powder cocaine (AOR 3.75; 95% CI 1.43–9.86), and perceiving themselves as less likely than other IDUs to get HIV (AOR 4.32; 95% CI 1.26–14.77). They had lower odds of ever being tested for HIV (AOR 0.25; 95% CI 0.08–0.80). Conclusion A high proportion of young heroin IDUs reported problematic prescription-type opioid use prior to initiating heroin use. Our study provides several avenues for future investigation to help further characterize this subset of IDUs and their risks and perceptions related to HIV and other blood-borne pathogens.

Effect of hepatitis C infection on progression of HIV disease and early response to initial antiretroviral therapy.

Objectives:To describe the effect of hepatitis C virus (HCV) on the progression of HIV disease and on early changes in the CD4 cell count and HIV viral load after HAART initiation. Design and methods:Data were from a longitudinal medical records review project conducted in over 100 US medical clinics from 1998 to 2004. We analysed data from HIV-infected patients who received antiretroviral therapy (ART), calculated adjusted hazard ratios describing the hazard of death or progression to an AIDS-defining opportunistic illness (AIDS–OI) associated with prevalent HCV infection, and estimated the change in CD4 cell count and HIV viral load after HAART initiation, stratified by HCV status. Results:A total of 10 481 HIV-infected individuals were followed for a median of 1.9 years; 19% had HCV. HCV infection was not associated with progression to AIDS–OI or death after controlling for important confounding conditions. Factors significantly confounding the risk of both death and diagnosis of an AIDS–OI were alcoholism, drug-induced hepatitis, and the type of ART prescribed. Acute and chronic hepatitis B infection confounded the risk of AIDS–OI diagnosis. During the 12 months after starting HAART, proportional increases in CD4 cell counts did not differ between HCV-infected and HCV-uninfected individuals. Likewise, the short-term change in viral load did not differ. Conclusion:In our cohort, HCV did not increase the risk of death or AIDS–OI, and did not affect the early immunological or virological response to initial HAART. Clinicians should evaluate patients with HCV for other, manageable problems, including alcoholism and other viral hepatitis.

Performance of Premarket Rapid Hepatitis C Virus Antibody Assays in 4 National Human Immunodeficiency Virus Behavioral Surveillance System Sites

SUMMARY Performance characteristics of rapid assays for hepatitis C virus antibody were evaluated in 4 National HIV Behavioral Surveillance System injection drug use sites. The highest assay-specific sensitivities achieved for the Chembio, MedMira and OraSure tests were 94.0%, 78.9%, and 97.4%, respectively; the highest specificities were 97.7%, 83.3%, and 100%, respectively. BACKGROUND The Centers for Disease Control and Prevention (CDC) estimates that 4.1 million Americans have been infected with hepatitis C virus (HCV) and 75%-80% of them are living with chronic HCV infection, many unaware of their infection. Persons who inject drugs (PWID) account for 57.5% of all persons with HCV antibody (anti-HCV) in the United States. Currently no point-of-care tests for HCV infection are approved for use in the United States. METHODS Surveys and testing for human immunodeficiency virus (HIV) and anti-HCV were conducted among persons who reported injection drug use in the past 12 months as part of the National HIV Behavioral Surveillance System in 2009. The sensitivity and specificity of point-of-care tests (finger-stick and 2 oral fluid rapid assays) from 3 manufacturers (Chembio, MedMira, and OraSure) were evaluated in field settings in 4 US cities. RESULTS Sensitivity (78.9%-97.4%) and specificity (80.0%-100.0%) were variable across assays and sites. The highest assay-specific sensitivities achieved for the Chembio, MedMira, and OraSure tests were 94.0%, 78.9% and 97.4%, respectively; the highest specificities were 97.7%, 83.3%, and 100%, respectively. In multivariate analysis, false-negative anti-HCV results were associated with HIV positivity for the Chembio oral assay (adjusted odds ratio, 8.4-9.1; P < .01) in 1 site (New York City). CONCLUSIONS Sensitive rapid anti-HCV assays are appropriate and feasible for high-prevalence, high-risk populations such as PWID, who can be reached through social service settings such as syringe exchange programs and methadone maintenance treatment programs.

Mortality Among Persons in Care With Hepatitis C Virus Infection: The Chronic Hepatitis Cohort Study (CHeCS), 2006–2010

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.

Effectiveness of 23-valent polysaccharide pneumococcal vaccine on pneumonia in HIV-infected adults in the United States, 1998-2003

Pneumococcal polysaccharide vaccine (PPV-23) has been recommended for HIV-infected adults. We investigated factors that could influence PPV-23 effectiveness against all-cause pneumonia in a longitudinal cohort of 23,255 HIV-infected adults receiving care during 1998--2003. Patients who received PPV-23 had a lower rate of pneumonia (IRR = 0.8; 95% CI: 0.8-0.9) than patients who had never been vaccinated, independent of recent CD4 count, HIV viral load, antiretroviral therapy, and history of pneumonia. However, PPV-23 provided no benefit when patients were vaccinated at HIV viral load > 100,000 copies/ml, irrespective of CD4 count at vaccination. Receipt of PPV-23 was associated with lower incidence of all-cause pneumonia.