HDV RNA assays: Performance characteristics, clinical utility, and challenges.

Coinfection with HBV and HDV results in hepatitis D, the most severe form of chronic viral hepatitis, frequently leading to liver decompensation and HCC. Pegylated interferon alpha, the only treatment option for chronic hepatitis D for many years, has limited efficacy. New treatments are in advanced clinical development, with one recent approval. Diagnosis and antiviral treatment response monitoring are based on detection and quantification of HDV RNA. However, the development of reliable HDV RNA assays is challenged by viral heterogeneity (at least 8 different genotypes and several subgenotypes), intrahost viral diversity, rapid viral evolution, and distinct secondary structure features of HDV RNA. Different RNA extraction methodologies, primer/probe design for nucleic acid tests, lack of automation, and overall dearth of standardization across testing laboratories contribute to substantial variability in performance characteristics of research-based and commercial HDV RNA assays. A World Health Organization (WHO) standard for HDV RNA, available for about 10 years, has been used by many laboratories to determine the limit of detection of their assays and facilitates comparisons of RNA levels across study centers. Here we review challenges for robust pan genotype HDV RNA quantification, discuss particular clinical needs and the importance of reliable HDV RNA quantification in the context of drug development and patient monitoring. We summarize distinct technical features and performance characteristics of available HDV RNA assays. Finally, we provide considerations for the use of HDV RNA assays in the context of drug development and patient monitoring.

Development of simple, rapid, and sensitive methods for detection of hepatitis C virus RNA from whole blood using reverse transcription loop-mediated isothermal amplification.

Hepatitis C virus (HCV) infection is an underdiagnosed global health problem. Diagnosis of current HCV infections typically requires testing for HCV RNA using high-complexity laboratory tests. Methods for the detection of HCV RNA that are simple, inexpensive, rapid, and compatible with use outside of a laboratory setting are very important in order to improve access to hepatitis C diagnostic testing and facilitate accelerated linkage to care. We developed and evaluated three simple workflows for extracting HCV RNA from small volumes of whole blood for use in a sensitive, pan-genotypic RT-LAMP assay. The water workflow uses osmotic stress to release HCV RNA and has a limit of detection of 4.3 log10(IU/mL) (95% CI 4.0-4.9). The heat workflow uses a heating step to release HCV RNA and has a limit of detection of 4.2 log10(IU/mL) (95% CI 3.8-5.1). The bead workflow, which uses chemical lysis of the sample and a streamlined paramagnetic solid phase reversible immobilization bead procedure for nucleic acid purification, has a limit of detection of 2.8 log10(IU/mL) (95% CI 2.5-3.4). When used to test whole blood spiked with HCV RNA-positive plasma samples in which most HCV levels were below 5.0 log10(IU/mL), the water, heat, and bead workflows detected HCV RNA in 69%, 75%, and 94% of samples, respectively. These workflows are compatible with visual lateral flow dipsticks, and each takes less than 60 min from sample to result. Each workflow can be performed with minimal and inexpensive equipment. With further procedural simplifications, these workflows may form the basis of assays for the point-of-care diagnosis of HCV infections.

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States.

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.

Evaluation of self-administered antigen testing in a college setting.

BACKGROUND: The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE). METHODS: Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability. RESULTS: Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high. CONCLUSIONS: Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.

In vitro characterization of six hepatitis B virus genotypes from clinical isolates using transfecting linear HBV genomes.

Hepatitis B virus (HBV) infection is a global public health problem with about 257 million chronically infected people and over 887000 deaths annually. In this study, 32 whole HBV genomes of various genotypes were amplified from clinical isolates to create transfection clones. The clones were sequenced, and their biological properties characterized by transfecting linear HBV clones into HepG2 cells. We analysed the SPI and SPII promotor regions, X-gene, BCP/PC sequences, core, preS/S and HBV polymerase sequences. HBV clones analysed in this study revealed differential replication kinetics of viral nucleic acids and expression of proteins. Sequence analysis of HBV clones revealed mutations in preS1, preS2 and S genes; deletion and insertion and point mutations in BCP/PC region; including novel and previously reported mutations. Among the patient samples tested, HBV genotype B clones were more likely to have higher frequencies of mutations, while sub-genotype A1 and A2 clones tended to have fewer mutations. No polymerase drug resistant mutations were seen. HBeAg mutations were primarily in the BCP/PC region in genotype B, but core truncations were found in genotype E. S gene mutations affecting HBsAg expression and detection were seen in all genotypes except A2. Using an HBV clone with repetitive terminal sequences and a SapI restriction site allowed us to analyse HBV analyte production in cell culture and characterize the genetics of viral phenotypes using complete HBV genomes isolated from serum/plasma samples of infected patients.

Unexpected Hepatitis B Virus Infection After Liver Transplantation - United States, 2014-2019.

Unexpected donor-derived hepatitis B virus (HBV) infection is defined as a new HBV infection in a recipient of a transplanted organ from a donor who tested negative for total antihepatitis B core antibody (total anti-HBc), hepatitis B surface antigen (HBsAg), and HBV DNA* before organ procurement. Such infections are rare and are associated with injection drug use among deceased donors (1). During 2014-2019, CDC received 20 reports of HBV infection among recipients of livers from donors who had no evidence of past or current HBV infection. Investigation included review of laboratory data and medical records. Fourteen of these new HBV infections were detected during 2019 alone; infections were detected a median of 38 (range = 5-116) weeks after transplantation. Of the 14 donors, 13 were hepatitis C virus (HCV)-seropositive† and had a history of injection drug use within the year preceding death, a positive toxicology result, or both. Because injection drug use is the most commonly reported risk factor for hepatitis C,§ providers caring for recipients of organs from donors who are HCV-seropositive or recently injected drugs should maintain awareness of infectious complications of injection drug use and monitor recipients accordingly (2). In addition to testing for HBV DNA at 4-6 weeks after transplantation, clinicians caring for liver transplant recipients should consider testing for HBV DNA 1 year after transplantation or at any time if signs and symptoms of viral hepatitis develop, even if previous tests were negative (2).

Determination of potential biotin interference on accuracy of results of serologic assays for various viral hepatitis markers.

Biotin taken orally can interfere with some diagnostic immunoassays, including those for thyroid hormones, ferritin, and markers of infectious disease. Assays affected are ones that use streptavidin-biotin in their design. The goal of our study was to examine the effect of biotin concentrations of up to 1200 ng/mL on three serological assays performed on VITROS 3600 system, Immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV), total anti-HAV, and IgM antibodies to hepatitis B virus core antigen (anti-HBc), by spiking serum samples with variable amounts of biotin. No false-negative results were generated with either concentration of biotin for total anti-HAV (65/65). Likewise, biotin caused no false-positive IgM anti-HAV results (59/59) with either concentration of biotin; however, 6.7% false negativity was found for IgM anti-HAV when samples were spiked with 1200 ng/mL of biotin. Conversely, 100% false positivity (30/30) was produced by biotin interference in total anti-HAV negative specimens with both concentrations of biotin. False negativity rate was 87.5% in IgM anti-HBc positive samples when biotin levels were at 1200 ng/mL. These data show that individuals taking biotin-containing supplements may test false-positive in some serologic assays using streptavidin-biotin chemistries. Further studies are warranted to determine the extent of biotin interference resulting in false-positive and negative results and their impact, if any, on surveillance and diagnostic settings.

Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014-2017.

We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.

Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN).

BACKGROUND & AIMS: Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. METHODS: The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis. The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome. RESULTS: The majority of patients was male (n = 979, 62%) and the mean age was 36.7 years (range 1-79, with 9% of patients younger than 20 years). Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%). Cirrhosis was reported in 48.7% of cases which included 13% of patients with previous or ongoing liver decompensation. Hepatocellular carcinoma (HCC) developed in 30 patients (2.5%) and 44 (3.6%) underwent liver transplantation. Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA. Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions. Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only. CONCLUSIONS: The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection.

Hepatitis B Reverse Seroconversion and Transmission in a Hemodialysis Center: A Public Health Investigation and Case Report.

In March 2013, public health authorities were notified of a new hepatitis B virus (HBV) infection in a patient receiving hemodialysis. We investigated to identify the source and prevent additional infections. We reviewed medical records, interviewed the index patient regarding hepatitis B risk factors, performed HBV molecular analysis, and observed infection control practices at the outpatient hemodialysis facility where she received care. The index patient's only identified hepatitis B risk factor was hemodialysis treatment. The facility had no other patients with known active HBV infection. One patient had evidence of a resolved HBV infection. Investigation of this individual, who was identified as the source patient, indicated that HBV reverse seroconversion and reactivation had occurred in the setting of HIV (human immunodeficiency virus) infection and a failed kidney transplant. HBV whole genome sequences analysis from the index and source patients indicated 99.9% genetic homology. Facility observations revealed multiple infection control breaches. Inadequate dilution of the source patient's sample during HBV testing might have led to a false-negative result, delaying initiation of hemodialysis in isolation. In conclusion, HBV transmission occurred after an HIV-positive hemodialysis patient with transplant-related immunosuppression experienced HBV reverse seroconversion and reactivation. Providers should be aware of this possibility, especially among severely immunosuppressed patients, and maintain stringent infection control.

High hepatitis C virus (HCV) prevalence among men who have sex with men (MSM) in Vietnam and associated risk factors: 2010 Vietnam Integrated Behavioural and Biologic Cross-Sectional Survey.

BACKGROUND: Hepatitis C virus (HCV) is an increasing health issue among key populations such as men who have sex with men (MSM). We sought to assess the burden of and risk factors for HCV among MSM in Vietnam. METHODS: We analysed behavioural and demographic data and stored specimens from MSM surveyed in four provinces through Vietnam's 2009-2010 Integrated Biologic and Behavioural Survey, which used probability-based, respondent-driven sampling. Commercial hepatitis B surface antigen (HBsAg) and HCV/antibody (HCV Ag/Ab) testing were performed on archived sera with follow-up PCR for HCV RNA and genotype determination. RESULTS: Among the 1588 MSM surveyed, the median (range) frequency, by province, of HCV Ag/Ab detection was 28.4% (13.7%-38.8%); 84.5% (83.1%-100%) among HIV-infected and 21.9% (8.9%-28.2%) among HIV-uninfected. HCV prevalence was higher in northern Hanoi and Hai Phong provinces than in southern Ho Chi Minh City and Chan Tho provinces. Among a convenience sample of 67 HCV Ag/Ab+ MSM, 67.2% were HCV RNA+; of 41 genotyped, 73.2% were genotype 1. HBsAg prevalence varied from 8.5% to 27.4%. In the multivariable logistic regression analysis, being HIV-infected (adjusted OR (aOR) 19.0; 7.0-51.9), ever having used injected drugs (aOR 4.4; 1.6-12.4) and age >25 years were significant risk factors for testing HCV Ag/Ab+. CONCLUSIONS: HCV infection in Vietnam appears to be high among MSM, particularly among HIV-infected MSM, with a north-south gradient. Given overlapping risk behaviours and associations between HCV and HIV, integrating HIV and HCV programme services to prevent both HIV and HCV transmission among MSM is indicated.

Notes from the Field: Hepatitis C Outbreak in a Dialysis Clinic--Tennessee, 2014.

Outbreaks of hepatitis C virus (HCV) infections can occur among hemodialysis patients when recommended infection control practices are not followed (1). On January 30, 2014, a dialysis clinic in Tennessee identified acute HCV in a patient (patient A) during routine screening and reported it to the Tennessee Department of Health. Patient A had enrolled in the dialysis clinic in March 2010 and had annually tested negative for HCV (including a last HCV test on December 19, 2012), until testing positive for HCV antibodies (anti-HCV) on December 18, 2013 (confirmed by a positive HCV nucleic acid amplification test). Patient A reported no behavioral risk factors, but did have multiple health care exposures.

Notes from the Field: Health Care-Associated Hepatitis A Outbreak - Texas, 2015.

On August 27-28, 2015, the Texas Department of State Health Services received calls from Fort Bend County and Harris County health departments requesting postexposure prophylaxis (PEP) recommendations for contacts of two nurses (patients A and B) with confirmed hepatitis A virus (HAV) infection. Both nurses had symptom onset during August 15-19 and worked for the same pediatric home health care agency in another jurisdiction. Because of the proximity of the onset dates, a common source exposure was suspected. The state and local health departments began an investigation to identify potentially exposed patients, their families, and other agency personnel; offer PEP; and identify the source of exposure.

Hepatitis C virus infection and co-infection with HIV among persons who inject drugs in 10 U.S. cities-National HIV Behavioral Surveillance, 2018.

BACKGROUND: Characterizing acute and chronic hepatitis C virus (HCV) infection and HIV/HCV co-infection among persons who inject drugs (PWID) can inform elimination efforts. METHODS: During 2018 National HIV Behavioral Surveillance in 10 U.S. metropolitan statistical areas (MSAs), PWID were recruited using respondent-driven sampling and offered a survey, HIV testing, and HCV antibody and RNA testing. We examined prevalence and associated characteristics of HCV infection and HIV/HCV co-infection. Associations were assessed using log-linked Poisson regression models with robust standard errors accounting for clustering by recruitment chain and adjusting for MSA and network size. RESULTS: Overall, 44.2% had current HCV infection (RNA detected), with 3.9% classified as acute infection (HCV antibody non-reactive/RNA detected) and 40.3% as chronic (HCV antibody reactive/RNA detected). Four percent had HIV/HCV co-infection. Current HCV infection was significantly higher among PWID who were male, White, injected >1 time/day, shared syringes in past year, and shared injection equipment in past year. PWID who were transgender, injecting >5 years, and most often injected speedball (heroin and cocaine together) or stimulants alone were more likely to have HIV/HCV co-infection. Among PWID who never previously had HCV infection, 9.9% had acute HCV infection. Among PWID who started injecting ≤5 years ago, 41.5% had already acquired HCV infection. CONCLUSIONS: Acute and chronic HCV infections were substantial among a sample of PWID in 10 U.S. MSAs. Accessibility to HCV RNA testing, promoting safer practices, and intervening early with harm reduction programs for recent injection initiates will be critical to disease elimination efforts for PWID.

Laboratory-based surveillance for hepatitis E virus infection, United States, 2005-2012.

To investigate characteristics of hepatitis E cases in the United States, we tested samples from persons seronegative for acute hepatitis A and B whose clinical specimens were referred to the Centers for Disease Control and Prevention during June 2005-March 2012 for hepatitis E virus (HEV) testing. We found that 26 (17%) of 154 persons tested had hepatitis E. Of these, 15 had not recently traveled abroad (nontravelers), and 11 had (travelers). Compared with travelers, nontravelers were older (median 61 vs. 32 years of age) and more likely to be anicteric (53% vs. 8%); the nontraveler group also had fewer persons of South Asian ethnicity (7% vs. 73%) and more solid-organ transplant recipients (47% vs. 0). HEV genotype 3 was characterized from 8 nontravelers and genotypes 1 or 4 from 4 travelers. Clinicians should consider HEV infection in the differential diagnosis of hepatitis, regardless of patient travel history.

Suppression of interferon-α signaling by hepatitis E virus.

UNLABELLED: The interferon (IFN) system is integral to the host response against viruses, and many viruses have developed strategies to overcome its antiviral effects. The effects of hepatitis E virus (HEV), the causative agent of hepatitis E, on IFN signaling have not been investigated primarily because of the nonavailability of an efficient in vitro culture system or small animal models of infection. We report here the generation of A549 cell lines persistently infected with genotype 3 HEV, designated as HEV-A549 cells and the effects HEV has on IFN-α-mediated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling. Treatment of HEV-A549 cells with 250, 500, and 1000 U/mL of IFN-α for 72 hours showed a dose-dependent reduction in HEV RNA levels by 10%, 20%, and 50%, respectively. IFN-α-stimulated genes coding for the antiviral proteins dsRNA-activated protein kinase (PKR) and 2',5'-oligoadenylate synthetase (2',5'-OAS) were down-regulated in IFN-α-treated HEV-A549 cells. HEV infection also prevented IFN-α-induced phosphorylation of STAT1. Regulation of STAT1 by HEV was specific, as phosphorylation of STAT2, tyrosine kinase (Tyk) 2, and Jak1 by IFN-α was unaltered. Additionally, STAT1 levels were markedly increased in HEV-A549 cells compared with naive A549 cells. Furthermore, binding of HEV open reading frame (ORF)3 protein to STAT1 in HEV-A549 cells was observed. HEV ORF3 protein alone inhibited IFN-α-induced phosphorylation of STAT1 and down-regulated the IFN-α-stimulated genes encoding PKR, 2',5'-OAS, and myxovirus resistance A. CONCLUSION: HEV inhibits IFN-α signaling through the regulation of STAT1 phosphorylation in A549 cells. These findings have implications for the development of new strategies against hepatitis E.

Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor.

Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. Methods: In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. Results: The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Conclusions: Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

Hepatitis B vaccine delivered by microneedle patch: Immunogenicity in mice and rhesus macaques.

Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination.

Laboratory diagnostics for hepatitis C virus infection.

Identification of prevalent infection by hepatitis C virus (HCV) is based serologically on detecting anti-HCV immunoglobulin G, using immunoassays, immunoblot assays, and, more recently, immunochromatography-based rapid tests. None discriminate between active and resolved HCV infection. Tests for detecting HCV RNA identify active HCV infection but are costly. Serologic assays for HCV antigens have been developed and show potential for diagnosis of active HCV infection, and their performance characteristics are undergoing evaluation. The diagnosis of acute HCV infection without the demonstration of seroconversion remains elusive.