When two viruses collide: coronavirus disease after hepatitis B virus reactivation.

The COVID-19 pandemic has exploded since the first cases were reported in Wuhan in December 2019, engulfing the globe. Many infected individuals are asymptomatic or have a mild or moderate disease. A subset of people with advanced age, the immunocompromised and those with chronic diseases, are prone to serious-to-critical illness. We report a fatal case of metastatic colorectal cancer survivor who developed COVID-19 after clinically reactivated hepatitis B virus (HBV) due to chemotherapy. The patient's COVID-19 illness was supposed to be related to her recent medical evaluation. Although being diagnosed with chronic HBV infection for decades, she was not treated with nucleotide analogue and the possibility to preclude HBV reactivation was missed. Moreover, infectious control practices must be draconian in order to save such a fragile population from infections.

High HBV-DNA serum levels are associated with type 2 diabetes in adults with positive HBsAg: An observational study.

Background: The prevalence of diabetes is higher in hepatitis B virus (HBV)-infected population. We aimed to examine the relationship between different serum HBV-DNA levels and type 2 diabetes in adults with positive HBV surface antigen (HBsAg). Methods: We conducted cross-sectional analyses of data obtaining from the Clinical Database System of Wuhan Union Hospital. Diabetes was defined by self-report of type 2 diabetes, fasting plasma glucose (FPG) ≥7mmol/L, or glycated hemoglobin (HbA1c) ≥6.5%. Binary logistic regression analyses were performed to investigate the factors associated with diabetes. Results: Among 12,527 HBsAg-positive adults, 2,144 (17.1%) were diabetic. Patients with serum HBV-DNA <100, 100-2000, 2000-20000 and ≥20000 IU/mL accounted for 42.2% (N=5,285), 22.6% (N=2,826), 13.3% (N=1,665) and 22.0% (N=2,751), respectively. The risk of type 2 diabetes, FPG ≥7mmol/L and HbA1c ≥6.5% in individuals with highly elevated serum HBV-DNA level (≥20000 IU/mL) were 1.38 (95% confidence interval [CI]: 1.16 to 1.65), 1.40 (95% CI: 1.16 to 1.68) and 1.78 (95% CI: 1.31 to 2.42) times relative to those with negative or lowly elevated serum HBV-DNA (<100 IU/mL). However, the analyses showed no association of moderately (2000-20000 IU/mL) to slightly (100-2000 IU/mL) raised serum HBV-DNA levels with type 2 diabetes (OR=0.88, P=0.221; OR=1.08, P=0.323), FPG ≥7mmol/L (OR=1.00, P=0.993; OR=1.11, P=0.250) and HbA1c ≥6.5% (OR=1.24, P=0.239; OR=1.17, P=0.300). Conclusion: In HBsAg-positive adults, highly elevated level rather than moderately to slightly raised levels of serum HBV-DNA is independently associated with an increased risk of type 2 diabetes.

Residual risk of mother-to-child transmission of HBV despite timely Hepatitis B vaccination: a major challenge to eliminate hepatitis B infection in Cambodia.

BACKGROUND: In countries with intermediate or high hepatitis B virus (HBV) endemicity, mother-to-child transmission (MTCT) represents the main route of chronic HBV infection. There is a paucity of information on HBV MTCT in Cambodia. This study aimed to investigate the prevalence of HBV infection among pregnant women and its MTCT rate in Siem Reap, Cambodia. METHODS: This longitudinal study included two parts, study-1 to screen HBsAg among pregnant women and study-2 to follow up babies of all HBsAg-positive and one-fourth of HBsAg-negative mothers at their delivery and six-month post-partum. Serum or dried blood spot (DBS) samples were collected to examine HBV sero-markers by chemiluminescent enzyme immunoassay (CLEIA), and molecular analyses were performed on HBsAg-positive samples. Structured questionnaires and medical records were used to examine the risk factors for HBV infection. MTCT rate was calculated by HBsAg positivity of 6-month-old babies born to HBsAg-positive mothers and ascertained by the homology of HBV genomes in mother-child pair at 6-month-old. RESULTS: A total of 1,565 pregnant women were screened, and HBsAg prevalence was 4.28% (67/1565). HBeAg positivity was 41.8% and was significantly associated with high viral load (p < 0.0001). Excluding subjects who dropped out due to restrictions during COVID-19, one out of 35 babies born to HBsAg-positive mothers tested positive for HBsAg at 6 months of age, despite receiving timely HepB birth dose and HBIG, followed by 3 doses of HepB vaccine. Hence the MTCT rate was 2.86%. The mother of the infected baby was positive for HBeAg and had a high HBV viral load (1.2 × 109 copies/mL). HBV genome analysis showed 100% homology between the mother and the child. CONCLUSIONS: Our findings illustrate the intermediate endemicity of HBV infection among pregnant women in Siem Reap, Cambodia. Despite full HepB vaccination, a residual risk of HBV MTCT was observed. This finding supports the recently updated guidelines for the prevention of HBV MTCT in 2021, which integrated screening and antiviral prophylaxis for pregnant women at risk of HBV MTCT. Furthermore, we strongly recommend the urgent implementation of these guidelines nationwide to effectively combat HBV in Cambodia.

Modified ARCHITECT® serologic assays enable plasma-level performance from dried blood spot samples.

Dried blood spots (DBSs) provide an alternative sample input for serologic testing. We evaluated DBSs for the ARCHITECT® hepatitis B surface antigen (HBsAg) NEXT, hepatitis B e-antigen (HBeAg), anti-hepatitis B core antigen (anti-HBc II), HIV antigen/antibody (Ag/Ab) Combo and AdviseDx SARS-CoV-2 IgG II assays. Assay performance with DBSs was assessed with or without assay modification and compared with on-market assay with plasma samples. DBS stability was also determined. HBsAg NEXT and HIV Ag/Ab Combo assays using DBSs showed sensitivity and specificity comparable to that of on-market assays. Modified HBeAg, anti-HBc II and SARS-CoV-2 IgG II DBS assays achieved performance comparable to on-market assays. Use of DBSs as input for high-throughput serologic assays is expected to have significant implications for improving population surveillance and increasing access to diagnostic testing.

The "humanized" N-glycosylation pathway in CRISPR/Cas9-edited Nicotiana benthamiana significantly enhances the immunogenicity of a S/preS1 Hepatitis B Virus antigen and the virus-neutralizing antibody response in vaccinated mice.

The recent SARS-CoV-2 pandemic has taught the world a costly lesson about the devastating consequences of viral disease outbreaks but also, the remarkable impact of vaccination in limiting life and economic losses. Vaccination against human Hepatitis B Virus (HBV), a major human pathogen affecting 290 million people worldwide, remains a key action towards viral hepatitis elimination by 2030. To meet this goal, the development of improved HBV antigens is critical to overcome non-responsiveness to standard vaccines based on the yeast-produced, small (S) envelope protein. We have recently shown that combining relevant immunogenic determinants of S and large (L) HBV proteins in chimeric antigens markedly enhances the anti-HBV immune response. However, the demand for cost-efficient, high-quality antigens remains challenging. This issue could be addressed by using plants as versatile and rapidly scalable protein production platforms. Moreover, the recent generation of plants lacking ß-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO), by CRISPR/Cas9 genome editing, enables production of proteins with "humanized" N-glycosylation. In this study, we investigated the impact of plant N-glycosylation on the immunogenic properties of a chimeric HBV S/L vaccine candidate produced in wild-type and FX-KO Nicotiana benthamiana. Prevention of ß-1,2-xylose and α-1,3-fucose attachment to the HBV antigen significantly increased the immune response in mice, as compared with the wild-type plant-produced counterpart. Notably, the antibodies triggered by the FX-KO-made antigen neutralized more efficiently both wild-type HBV and a clinically relevant vaccine escape mutant. Our study validates in premiere the glyco-engineered Nicotiana benthamiana as a substantially improved host for plant production of glycoprotein vaccines.

Aerosol formation during processing of potentially infectious samples on Roche immunochemistry analyzers (cobas e analyzers) and in an end-to-end laboratory workflow to model SARS-CoV-2 infection risk for laboratory operators.

Objectives: To assess aerosol formation during processing of model samples in a simulated real-world laboratory setting, then apply these findings to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess the risk of infection to laboratory operators. Design: This study assessed aerosol formation when using cobas e analyzers only and in an end-to-end laboratory workflow. Recombinant hepatitis B surface antigen (HBsAg) was used as a surrogate marker for infectious SARS-CoV-2 viral particles. Using the HBsAg model, air sampling was performed at different positions around the cobas e analyzers and in four scenarios reflecting critical handling and/or transport locations in an end-to-end laboratory workflow. Aerosol formation of HBsAg was quantified using the Elecsys® HBsAg II quant II immunoassay. The model was then applied to SARS-CoV-2. Results: Following application to SARS-CoV-2, mean HBsAg uptake/hour was 1.9 viral particles across the cobas e analyzers and 0.87 viral particles across all tested scenarios in an end-to-end laboratory workflow, corresponding to a maximum inhalation rate of <16 viral particles during an 8-hour shift. Conclusion: Low production of marker-containing aerosol when using cobas e analyzers and in an end-to-end laboratory workflow is consistent with a remote risk of laboratory-acquired SARS-CoV-2 infection for laboratory operators.

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

High Seroprevalence of Hepatitis B and C Virus Infections among Pregnant Women Attending Antenatal Clinic in Borumeda General Hospital, Northeast Ethiopia.

Background: Viral hepatitis are considered as the cause of solemn health problem for the human kind, particularly among pregnant women in the 21th century. Therefore, this study is aimed at determining the seroprevalence of HBV and HCV infection among pregnant women attending at Borumeda General Hospital, Dessie, Northeast Ethiopia. Methods: An institution-based cross-sectional study was conducted at Borumeda General Hospital from April to May, 2020. A consecutive total of 124 pregnant women who were attending at the antenatal clinic (ANC) of the hospital were included. A structured questionnaire was used to assess the associated factors and some sociodemographic characteristics. Five milliliters of venous blood was collected from each study participant, and a laboratory test using a rapid HBsAg and anti-HCV kit was done. The data were analyzed using SPSS software version 22. Results: The mean age of the study subjects was 25.81 (±5.967) years. The overall seroprevalence of either HBV or HCV infections among the study participants was 14 (11.3%). HBsAg and anti-HCV were positive among 10 (8.1%) and 4 (3.2%) study participants, respectively. There was no coinfection result between HBV and HCV among pregnant women. Pregnant women who had abortion history [AOR 5.723; 95% CI 1.100-29.785, P value = 0.038] and hospitalization history with IV medication [AOR 6.939; 95% CI 1.017-47.322, P value = 0.048] exhibited statistically significant association with HBV infection. Conclusions: Seroprevalence of HBV and HCV infections among pregnant women was high, and the rate of HBV particularly can be considered in the high endemic category of the WHO classification scheme. Continuous screening of pregnant mothers, provision of hepatitis B vaccine for females at the child-bearing age, and health education to create awareness about HBV and HCV should be implemented.

RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge.

The ongoing COVID-19 pandemic has contributed largely to the global vaccine disparity. Development of protein subunit vaccines can help alleviate shortages of COVID-19 vaccines delivered to low-income countries. Here, we evaluated the efficacy of a three-dose virus-like particle (VLP) vaccine composed of hepatitis B surface antigen (HBsAg) decorated with the receptor binding domain (RBD) from the Wuhan or Beta SARS-CoV-2 strain adjuvanted with either aluminum hydroxide (alum) or squalene in water emulsion (SWE). RBD HBsAg vaccines were compared to the standard two doses of Pfizer mRNA vaccine. Alum-adjuvanted vaccines were composed of either HBsAg conjugated with Beta RBD alone (ß RBD HBsAg+Al) or a combination of both Beta RBD HBsAg and Wuhan RBD HBsAg (ß/Wu RBD HBsAg+Al). RBD vaccines adjuvanted with SWE were formulated with Beta RBD HBsAg (ß RBD HBsAg+SWE) or without HBsAg (ß RBD+SWE). Both alum-adjuvanted RBD HBsAg vaccines generated functional RBD IgG against multiple SARS-CoV-2 variants of concern (VOC), decreased viral RNA burden, and lowered inflammation in the lung against Alpha or Beta challenge in K18-hACE2 mice. However, only ß/Wu RBD HBsAg+Al was able to afford 100% survival to mice challenged with Alpha or Beta VOC. Furthermore, mice immunized with ß RBD HBsAg+SWE induced cross-reactive neutralizing antibodies against major VOC of SARS-CoV-2, lowered viral RNA burden in the lung and brain, and protected mice from Alpha or Beta challenge similarly to mice immunized with Pfizer mRNA. However, RBD+SWE immunization failed to protect mice from VOC challenge. Our findings demonstrate that RBD HBsAg VLP vaccines provided similar protection profiles to the approved Pfizer mRNA vaccines used worldwide and may offer protection against SARS-CoV-2 VOC. IMPORTANCE Global COVID-19 vaccine distribution to low-income countries has been a major challenge of the pandemic. To address supply chain issues, RBD virus-like particle (VLP) vaccines that are cost-effective and capable of large-scale production were developed and evaluated for efficacy in preclinical mouse studies. We demonstrated that RBD-VLP vaccines protected K18-hACE2 mice against Alpha or Beta challenge similarly to Pfizer mRNA vaccination. Our findings showed that the VLP platform can be utilized to formulate immunogenic and efficacious COVID-19 vaccines.

Prevalence of Viral Hepatitis in Unselected, Consecutively Enrolled Patients Hospitalised for SARS-CoV-2.

Diagnosing people living with chronic viral hepatitis is challenging due to the absence of symptoms as long as liver decompensated cirrhosis come out. The aim of this retrospective study was to evaluate the prevalence of HBV and/or HCV infections in a non-selected population, hospitalised for SARS-CoV-2 infection in a tertiary care hospital in Northern Italy. During the study period 1,429 patients were admitted to hospital for SARS-CoV-2 infection, serologic tests for HBV and/or HCV were available for 382 (27%) patients and 3 were excluded due to their previous known serologic status. Among 379 patients, 235 (62%) were male, median age was 70 years (range 21-103), 360 (95%) were Caucasian. Among them, 372/379 (98%) were screened for HBsAg, 320/379 (84%) for HBcAb. HBsAg was positive in 2/372 (0.5%, 95% CI 0.0006-0.02) patients (only in one HBV-DNA was performed that was negative), while HBcAb was found positive in 55/320 (17%, 95% CI 0.13-0.22). Among 370/379 (98%) patients screened for HCV, 11/370 (3%, 95% CI 0.02-0.05) had positive HCV-Ab. Five out of 11 (45%) were tested for HCV-RNA that resulted positive in two patients (0.5%, 95% CI 0.0006-0.02). Considering this data, even though the screening was performed in only 27% of study population, a tailored screening in people with known risk factors for hepatitis might be preferable to universal screening in low prevalence areas. Also a prompt diagnostic workout should begin in case of clinical or laboratory suspicion of hepatitis and in those starting immunosuppressive treatments.

Long-term effect of chronic hepatitis B on mortality in HIV-infected persons in a differential HBV transmission setting.

BACKGROUND: There remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals. METHODS: Using a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan-Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality. RESULTS: Of 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4-50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1-2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort. CONCLUSIONS: HBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis.

Adult immunization against hepatitis B: Does the number of jabs matter?

BACKGROUND: At least one-half of adults beginning an immunization series with a three-dose hepatitis B virus (HBV) vaccine (ENGERIX-B, RECOMBIVAX-B) have been reported not to receive the third dose. Use of a two-dose vaccine may improve adherence and lead to greater overall levels of seroprotection. OBJECTIVE: To examine expected levels of adherence and overall seroprotection at one year among adults in routine clinical settings beginning an immunization series with either ENGERIX-B or the two-dose HBV vaccine, HEPLISAV-B. METHODS: Decision-analytic model comparing expected levels of adherence and overall seroprotection at one year among a hypothetical cohort of one million previously unvaccinated adults aged ≥ 30 years receiving first doses of either ENGERIX-B or HEPLISAV-B in a routine clinical setting. We stratified the population by age (30-49 years vs ≥ 50 years) to allow for possible differences in adherence and seroprotection. We estimated our model using published adherence rates for HBV vaccines, and reported seroprotection rates by number of doses administered. We also compared total expected costs of HBV immunization with each vaccine. RESULTS: Use of a two-dose rather than three-dose HBV vaccine would increase the expected number of adults seroprotected at one year by 275,000 per one million persons beginning immunization series, largely reflecting a gain of 290,000 in the expected number of persons fully vaccinated. Results were similar for the two age groups. While the cost per dose of HEPLISAV-B exceeds that of ENGERIX-B, its estimated mean cost per person seroprotected at one year is $50-$70 (∼15%) lower. CONCLUSIONS: Use of a two-dose HBV vaccine would increase the number of adults fully seroprotected at one year compared with the number expected with a three-dose vaccine. Notwithstanding its higher unit cost, mean expected cost per person seroprotected is substantially lower for HEPLISAV-B than ENGERIX-B as a result of much higher levels of seroprotection.

Acute hepatitis B in pregnancy with surprisingly rapid clearance of serum HBs antigen associated with a favourable outcome.

Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease.

Management of hepatitis B virus reactivation due to treatment of COVID-19.

The world has made significant progress in developing novel treatments for COVID-19 since the pandemic began. Some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. This review summarizes the risk and management of HBVr due to different treatments of COVID-19 in patients who have current or past HBV infection. Abnormal liver function tests are common during COVID-19 infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis. Data, however, remain scarce regarding the specific use of immunosuppressive therapies in COVID-19 patients with HBV infection. Some results are mainly extrapolated from patients receiving the same agents in other diseases. HBVr is a potentially life-threatening event following profound immunosuppression by COVID-19 therapies. Future studies should explore the use of immunosuppressive therapies in COVID-19 patients with HBV infection and the impact of antiviral prophylaxis on the risk of HBVr.

Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico.

INTRODUCTION AND OBJECTIVES: The emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study. MATERIAL AND METHODS: Cross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg). RESULTS: Out of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status. CONCLUSIONS: In this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.

Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come.

The impact of the first, second and third waves of covid-19 on hepatitis B and C testing in Ontario, Canada.

The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%-75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti-HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID-19 long after the pandemic has resolved.

Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection. / Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2.

AIMS: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients. METHOD: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection. RESULTS: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0-104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19). CONCLUSION: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.

Prospective clinical trial of hepatitis B vaccination for children with hematological malignancies: a study on the safety and immunogenicity efficacy.

Children with hematological malignancies are at increased risk of hepatitis B virus infection. This study assessed the immunogenicity and safety profile of HBV vaccination in pediatric hemato-oncological children. A nonrandomized interventional study was conducted from January 2017 to February 2020 in Shanghai, China. Seventy-three pediatric hemato-oncological children with hepatitis B surface antibody (anti-HBs) titers <10 mIU/ml were recruited. The participants received three doses of recombinant HBV vaccine according to the 0-, 1-, and 6- month immunization schedule. Adverse events following immunization and anti-HBs titers (at baseline, 1 month, and 6 months after inoculation) were recorded. Forty-three males and thirty females with median ages of 9.12 and 9.60 years, respectively, were included. The mean anti-HBs titer was 4.88 ± 2.61 mIU/ml, 893.12 ± 274.12 mIU/ml, and 711.45 ± 337.88 mIU/ml at baseline, one month, and six months after inoculation, respectively (P< .001). A total of fourteen adverse events following immunization were reported, and among them, 5 (6.85%), 5 (6.85%), and 4 (5.48%) events were reported after the first, second, and third inoculation, respectively (P= .927). In conclusions, the HBV vaccine is immunogenic and safe in children with hematological malignancies. It is worth noting that the anti-HBs titer was decreased at the 6-month follow-up, and periodic monitoring of the anti-HBs titer accompanied by timely booster vaccination should be carefully considered.Abbreviations: AEFI: Adverse events following immunization; HBV: Hepatitis B virus; Anti-HBs: Antibody against hepatitis B surface antigen; HBsAg: Hepatitis B surface antigen; APC: Antigen-presenting cell; HSCT: Hemopoietic stem cell transplantation; COVID-19: Corona Virus Disease 2019.