Epidemiology and Diagnostics of Hepatitis Viruses

Introduction: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. Aims: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. Methods: All blood donations were screened in pools of 12–24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X − 1) where available. Results: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01–2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X − 1). Two donors were HEV IgG-positive in the X − 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. Conclusion: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed. Full article

HepB LiveTest is a machine learning decision support system developed for the early detection of hepatitis B virus (HBV). However, there is a lack of evidence on its generalisability. In this study, we aimed to externally assess the clinical validity and portability of HepB LiveTest in predicting HBV infection among independent patient cohorts from Nigeria and Australia. The performance of HepB LiveTest was evaluated by constructing receiver operating characteristic curves and estimating the area under the curve. Delong’s method was used to estimate the 95% confidence interval (CI) of the area under the receiver-operating characteristic curve (AUROC). Compared to the Australian cohort, patients in the derivation cohort of HepB LiveTest and the hospital-based Nigerian cohort were younger (mean age, 45.5 years vs. 38.8 years vs. 40.8 years, respectively; p < 0.001) and had a higher incidence of HBV infection (1.9% vs. 69.4% vs. 57.3%). In the hospital-based Nigerian cohort, HepB LiveTest performed optimally with an AUROC of 0.94 (95% CI, 0.91–0.97). The model provided tailored predictions that ensured most cases of HBV infection did not go undetected. However, its discriminatory measure dropped to 0.60 (95% CI, 0.56–0.64) in the Australian cohort. These findings indicate that HepB LiveTest exhibits adequate cross-site transportability and clinical validity in the hospital-based Nigerian patient cohort but shows limited performance in the Australian cohort. Whilst HepB LiveTest holds promise for reducing HBV prevalence in underserved populations, caution is warranted when implementing the model in older populations, particularly in regions with low incidence of HBV infection. Full article

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). Dual HDV/HBV infection is associated with down-regulated HBV replication and fast progression to severe liver disease. Although HDV is transmissible through exposure to infected blood, data about HDV infection in blood donors remain scarce. Between 2011 and 2021, 869,633 donations were collected from prequalified donors in Dalian, China. In total, 1060 (0.12%) were confirmed HBsAg and/or HBV DNA-reactive. Subsequently, anti-HDV IgG was tested in 2175 donations, including 65 that tested HBsAg+ pre donation, 1017 confirmed HBV-positive (507 HBsAg+/HBV DNA+, 33 HBsAg+/DNA−, 477 HBsAg-/DNA+ (451 occult (OBI) and 26 acute infections)), 327 viral DNA non-repeated-reactive, 397 anti-HBc-only, and 369 anti-HBs-only. Two (0.09%) samples tested anti-HDV IgG weakly reactive but were unconfirmed by IgM and IgG repeat testing with alternative assays, suggesting an initial false reactivity. In addition, HDV testing in a subgroup of confirmed OBI donors, comprising 451 donors from Dalian and 126 archived samples of OBI donors from around the world, showed only one non-Chinese donor to be repeatedly anti-HDV-reactive, suggesting that HDV/HBV coinfection does not play a significant role in the genesis of OBI. The overall data suggested an extremely low prevalence of HDV infection among blood donors in Liaoning province, Northeast China. Full article

Mongolia has one of the highest viral hepatitis infection (B, C, and D) rates in the world. The aims of this study were to increase awareness of this disease and promote viral hepatitis screening in the Mongolian community living in Spain. Through a native community worker, Mongolian adults were invited to a community program consisting of an educational activity, an epidemiological questionnaire, and rapid point-of-care testing for hepatitis B and C. In those testing positive, blood extraction was performed to determine serological and virological parameters. In total, 280 Mongolians were invited to the program and 222 (79%) attended the event: 139 were women (63%), mean age was 42 years, and 78 (35%) had viral hepatitis risk factors. Testing found 13 (5.8%) anti-HCV-positive individuals, 1 with detectable HCV RNA (0.5%), 8 HBsAg-positive (3.6%), and 7 with detectable HBV DNA (3.1%). One additional individual had HBV/HCV co-infection with detectable HBV DNA and HCV RNA. Two subjects had hepatitis B/D co-infection (0.9%). The knowledge questionnaire showed a 1.64/8-point (20.5%) increase in correct answers after the educational activity. In summary, a viral hepatitis community program was feasible and widely accepted. It increased awareness of this condition in the Mongolian community in Spain and led to linkage to care in 22 participants, 50% of whom were unaware of their infection. Full article

Hepatitis B surveillance is essential to achieving Canada’s goal of eliminating hepatitis B by 2030. Hepatitis B rates, association of infection with vaccine age-eligibility, and risk factors were analyzed among 1,401,603 first-time Canadian blood donors from 2005 to 2020. Donors were classified as having likely chronic or likely resolved/occult infections based on hepatitis B surface antigen, anti-hepatitis B core antigen, and hepatitis B nucleic acid test results. Likely chronically infected and control donors (ratio 1:4) participated in risk-factor interviews. The 2019 rate of likely chronic infection was 61.9 per 100,000 (95% CI 46.5–80.86) and 1449.5 per 100,000 for likely resolved/occult infections (95% CI 1370.7–1531.7). Likely chronic infections were higher in males (OR 3.2; 95% CI 2.7–3.7) and the vaccine-ineligible birth cohort (OR 1.9; 95% CI 1.6–2.2). The main risk factors were living with someone who had hepatitis (OR 12.5; 95% CI 5.2–30.0) and ethnic origin from a high-prevalence country (OR 8.4; 95% CI 5.9–11.9). Undiagnosed chronic hepatitis B may be more prevalent in Canada than currently determined by traditional passive hepatitis B reporting. Blood donor data can be useful in informing hepatitis B rates and evaluating vaccination programs in Canada. Full article

Foodborne viruses are an important threat to food safety and public health. Globally, there are approximately 5 million cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) every year. HAV is responsible for numerous food-related viral outbreaks worldwide, while HEV is an emerging pathogen with a global health burden. The reported HEV cases in Europe have increased tenfold in the last 20 years due to its zoonotic transmission through the consumption of infected meat or meat products. HEV is considered the most common cause of acute viral hepatitis worldwide currently. This review focuses on the latest findings on the foodborne transmission routes of HAV and HEV and the methods for their detection in different food matrices. Full article

The present-day management of hepatitis B virus (HBV) infection relies on constant and appropriate monitoring of viral activity, disease progression and treatment response. Traditional HBV infection biomarkers have many limitations in predicting clinical outcomes or therapy success. Quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker that can be used in solving multiple diagnostic problems. It was shown to correlate well with infection phases, level of hepatic inflammation and fibrosis, exacerbations during chronic infection and presence of occult infection. Further, the level of qAnti-HBc was recognised as predictive of spontaneous or therapy-induced HBeAg and HBsAg seroclearance, relapse after therapy discontinuation, re-infection after liver transplantation and viral reactivation upon immunosuppression. However, qAnti-HBc cannot be relied upon as a single diagnostic test to solve all dilemmas, and its diagnostic and prognostic power can be much improved when combined with other diagnostic biomarkers (HBV DNA, HBeAg, qHBsAg and anti-HBs antibodies). The availability of commercial qAnti-HBc diagnostic kits still needs to be improved. The comparison of results from different studies and definitions of universal cut-off values continue to be hindered because many methods are only semi-quantitative. The clinical utility of qAnti-HBc and the methods used for its measurement are the focus of this review. Full article