Challenges of hepatitis B treatment in rural Sub-Saharan Africa: Treatment initiation and outcomes from a public hospital-based clinic in Kono, Sierra Leone.

Despite a high prevalence, there are few successful models for de-centralizing diagnosis and treatment of chronic hepatitis B virus (HBV) infection among rural communities in Sub-Saharan Africa. We report baseline characteristics and 1 year retention outcomes for patients enrolled in a HBV clinic integrated within chronic disease services in a rural district hospital in Sierra Leone. We conducted a retrospective cohort study of patients with HBV infection enrolled between 30 April 2019 and 30 April 2021. Patients were eligible for 1 year follow-up if enrolled before 28 February 2020. Treatment eligibility at baseline was defined as cirrhosis (diagnosed by clinical criteria of decompensated cirrhosis, ultrasonographic findings or aspartate-aminotransferase-to-platelet ratio >2) or co-infection with HIV or HCV. Retention in care was defined as a documented follow-up visit at least 1 year after enrolment. We enrolled 623 individuals in care, median age of 30 years (IQR 23-40). Of 617 patients with available data, 97 (15.7%) had cirrhosis. Treatment was indicated among 113 (18.3%) patients and initiated among 74 (65.5%). Of 39 patients eligible for 1 year follow-up on treatment at baseline, 20 (51.3%) were retained at 1 year, among whom 12 (60.0%) had documented viral suppression. Among the 232 patients not initiated on treatment eligible for 1 year follow-up, 75 (32.3%) were retained at 1 year. Although further interventions are required to improve outcomes, our findings demonstrated feasibility of retention and treatment of patients with HBV infection in a rural district in Sub-Saharan Africa, when integrated with other chronic disease services.

Correlation between COVID-19 and hepatitis B: A systematic review.

BACKGROUND: There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public health threat in current society. Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV can cause liver damage, and current findings on whether HBV infection increases disease severity in COVID-19 patients are inconsistent, and whether SARS-CoV-2 infection accelerates hepatitis B progression or leads to a worse prognosis in hepatitis B patients has not been adequately elucidated. AIM: To explore the complex relationship between COVID-19 and hepatitis B in order to inform the research and management of patients co-infected with SARS-CoV-2 and HBV. METHODS: An experienced information specialist searched the literature in the following online databases: PubMed, China National Knowledge Infrastructure, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, and ScienceDirect. The literature published from December 2019 to September 1, 2022 was included in the search. We also searched medRxiv and bioRxiv for gray literature and manually scanned references of included articles. Articles reporting studies conducted in humans discussing hepatitis B and COVID-19 were included. We excluded duplicate publications. News reports, reports, and other gray literature were included if they contained quantifiable evidence (case reports, findings, and qualitative analysis). Some topics that included HBV or COVID-19 samples but did not have quantitative evidence were excluded from the review. RESULTS: A total of 57 studies were eligible and included in this review. They were from 11 countries, of which 33 (57.9%) were from China. Forty-two of the 57 studies reported abnormalities in liver enzymes, three mainly reported abnormalities in blood parameters, four indicated no significant liver function alterations, and another eight studies did not provide data on changes in liver function. Fifty-seven studies were retrospective and the total number of co-infections was 1932, the largest sample size was 7723, and the largest number of co-infections was 353. Most of the studies suggested an interaction between hepatitis B and COVID-19, while 12 studies clearly indicated no interaction between hepatitis B and COVID-19. Six of the 57 studies clearly reported HBV activation. Six studies were related to liver transplant patients. CONCLUSION: There is some association between COVID-19 and hepatitis B. Future high-quality randomized trials are needed to further elucidate the interaction between COVID-19 and hepatitis B.

Rapid quantification assay of hepatitis B virus DNA in human serum and plasma by Fully Automated Genetic Analyzer µTASWako g1.

Real-time monitoring of serum hepatitis B virus (HBV) levels is essential for the management of patients with chronic HBV infection in clinical practice, including monitoring the resistance of anti-HBV nucleotide analog or the detection of HBV reactivation. In this context, serum HBV deoxyribonucleic acid (DNA) quantification should be rapidly measured. A rapid HBV DNA quantification assay was established on the Fully Automated Genetic Analyzer, µTASWako g1. The assay performs automated sample preparation and DNA extraction, followed by the amplification and detection of quantitative polymerase chain reaction (PCR) combined with capillary electrophoresis (qPCR-CE) on integrated microfluidic chip. This study aimed to evaluate the analytical and clinical performance of HBV DNA assay on the µTASWako g1 platform in human serum and EDTA-plasma. The HBV DNA assay has a linear quantitative range from 20 to 108 IU/mL of HBV DNA with standard deviation (SD) of ≤0.14 log10 IU/mL. The limits of detection of the assay were 4.18 for the serum and 4.35 for EDTA-plasma. The HBV assay demonstrated the equivalent performance in both human serum and EDTA-plasma matrices. The HBV genotypes A to H were detected with an accuracy of ±0.34 log10 IU/mL. In quantification range, the HBV DNA assay was correlated with Roche cobas AmpliPrep/cobas TaqMan Ver2.0 (CAP/CTM v2) (r = 0.964). The mean difference (µTASWako g1-CAP/CTM v2) of the reported HBV DNA was -0.01 log10 IU/mL. Overall, the sensitivity, accuracy, and precision of the µTASWako g1 HBV assay were comparable to the existing commercial HBV DNA assay, and the assay can be completed within 110 min. This evaluation suggests that the HBV DNA assay on the µTASWako g1 is potentially applied for alternative method of the HBV viral load test, in particular with the advantage of the HBV DNA result availability within 2 h, improving the HBV infection management.

Thrombotic thrombocytopenic purpura developed after pegylated interferon treatment for hepatitis B infection.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia. It is related to severe deficiency in ADAMTS13, which is usually acquired via ADAMTS13 autoantibodies or inherited via mutations of the ADAMTS13 gene. The etiology of acquired TTP including HIV infection, pregnancy, autoimmune disease, organ transplantation, drugs, malignancy and so on. Here, we firstly reported a patient diagnosed as acquired TTP after pegylated interferon therapy for hepatitis B and COVID-19 vaccination. CASE PRESENTATION: A 36-year-old male attended to our unit with a five-day history of intermittent hematuria and progressive fatigue on January 5th, 2022. He had a 13 years history of hepatitis B infection and undergone pegylated interferon treatment (which was paused for two months because of COVID-19 vaccination) for nearly 3 years. Laboratory evaluation revealed a haemoglobin level of 61 g/L, platelet count of 11 × 109/L, lactate dehydrogenase 2133 U/L. The direct and indirect Coombs test were both negative. On a peripheral blood smear, there were about 18.8% schistocytes. Meanwhile, the results of ADAMTS 13 activity and antibody were < 5% and 181.34 ng/ml (131.25-646.5), respectively CONCLUSION: This case firstly reported the rare complication of TTP after pegylated interferon treatment for hepatitis B and COVID-19 vaccine injection. This unique sign warrants more attention as an early cue of diagnosis of TTP and be aware of the rarity adverse effect of interferon therapy and COVID-19 vaccination.

Prevalence of undiagnosed hepatitis B virus infection in patients with COVID-19A single center retrospective study.

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.

Epidemiological and clinical aspects of hepatitis B virus infection in Italy over the last 50 years.

A relevant gradual reduction of both the incidence rate of acute hepatitis B (AHB) and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years, due to substantial epidemiological changes: Improvement in socioeconomic and hygienic conditions, reduction of the family unit, accurate screening of blood donations, abolition of re-usable glass syringes, hepatitis B virus (HBV)-universal vaccination started in 1991, use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998, and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections. As an example, AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020. Unfortunately, the coronavirus disease 2019 (COVID-19) pandemic has interrupted the trend towards HBV eradication. In fact, several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening, diagnosis, clinical management, and nucleo(t)side analogue therapy in the COVID-19 pandemic, mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), movement restrictions, and reduced gains from job loss. In addition, one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.

A Rapid Review of Interventions to Increase Hepatitis B Testing, Treatment, and Monitoring among Migrants Living in Australia.

Chronic hepatitis B (CHB) disproportionately affects migrants with low health literacy and help-seeking behaviour living in high-income countries. Evidence of effective interventions is required to increase hepatitis B (HBV) testing, treatment, and monitoring. Available evidence from Medline, Embase, Scopus, Google, and Google Scholar was identified, collated, and synthesised. Inclusion criteria included grey and peer-reviewed literature published in English between January 2012 and December 2021. Systematic reviews and meta-analyses were excluded. Seventeen peer-reviewed articles met the inclusion criteria. Most interventions were conducted at the individual level and were typically outreach testing initiatives. One study was conducted at a structural level. All studies were successful in encouraging HBV screening uptake, and 10 studies demonstrated effective linkage to care. Two studies showed evidence of monitoring participants post-intervention. Most interventions had more female than male participants. Interventions conducted across community and clinical-based settings had more participants engage in screening and/or linkage to care in community settings. Effective interventions to prevent HBV transmission and CHB-related morbidity and mortality were approaches that utilised linguistic-specific and culturally appropriate resources to successfully engage migrants. Community outreach programmes that educate participants about HBV transmission, screening, and treatment can promote community dialogue and understanding to reduce stigma and discrimination.

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.

A case of reactivation of hepatitis B presenting with exudative ascites.

Hepatitis B virus infection is a global problem and causes several liver diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Though uncommon, some immune mediated extra-hepatic manifestations may develop during the infection. Exudative ascites during HBV infection is one such.

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.

Progress on global hepatitis elimination targets.

In 2016, the World Health Assembly adopted a Global Health Sector Strategy on viral hepatitis, with targets set for the years 2020 and 2030 to achieve hepatitis elimination. The main target of hepatitis elimination strategy is to reduce the incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) by 90% and mortality by 65% in 2030. In last 5 years, the number of people receiving HCV treatment has increased from 1 million to 9.4 million; however, this number is far from the 2030 target of 40 million people receiving HCV treatment. HBV and HCV incidence rates are down from 1.4 million to 1.1 million annual deaths but this is far from the 2030 target of < 0.5 million deaths. The coronavirus disease 2019 pandemic has severely affected the efforts in the fight against hepatitis. No major donor has committed to investing in the fight against hepatitis. Time is running out. There is a need to speed up efforts in the fight against hepatitis to achieve hepatitis elimination by 2030.

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 virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

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.

Long-Term Safety of Rituximab (Risks of Viral and Opportunistic Infections).

PURPOSE OF REVIEW: We reviewed the current data on infections associated with rituximab use published over the last 5 years. RECENT FINDINGS: New literature was available on rates of serious infections, Hepatitis B reactivation and screening, and infection with Severe Acute Respiratory Syndrome Coronavirus 2. Rates of infection varied by study and population, however, higher risk of infection in patients with underlying rheumatologic diseases was seen in those who required a therapy switch, had a smoking history, and those undergoing retreatment who had a serious infection with their first course of therapy. With regards to HBV, the proportion of patients screened continues to be inadequate. Despite the upfront cost, HBV screening and prophylaxis were found to be cost effective. There is still limited data regarding COVID-19 severity in the setting of rituximab, however, rituximab, especially in combination with steroids, may lead to more severe disease and higher mortality.

The global impact of the COVID-19 pandemic on the prevention, diagnosis and treatment of hepatitis B virus (HBV) infection.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is accruing on the broader consequences of such interventions on economic and public health inequalities, as well as on pre-existing programmes targeting endemic pathogens. We provide an overview of the impact of the ongoing COVID-19 pandemic on hepatitis B virus (HBV) programmes globally, focusing on the possible consequences for prevention, diagnosis and treatment. Ongoing disruptions to infrastructure, supply chains, services and interventions for HBV are likely to contribute disproportionately to the short-term incidence of chronic hepatitis B, providing a long-term source of onward transmission to future generations that threatens progress towards the 2030 elimination goals.

A Review of Piezoelectric and Magnetostrictive Biosensor Materials for Detection of COVID-19 and Other Viruses.

The spread of the severe acute respiratory syndrome coronavirus has changed the lives of people around the world with a huge impact on economies and societies. The development of wearable sensors that can continuously monitor the environment for viruses may become an important research area. Here, the state of the art of research on biosensor materials for virus detection is reviewed. A general description of the principles for virus detection is included, along with a critique of the experimental work dedicated to various virus sensors, and a summary of their detection limitations. The piezoelectric sensors used for the detection of human papilloma, vaccinia, dengue, Ebola, influenza A, human immunodeficiency, and hepatitis B viruses are examined in the first section; then the second part deals with magnetostrictive sensors for the detection of bacterial spores, proteins, and classical swine fever. In addition, progress related to early detection of COVID-19 (coronavirus disease 2019) is discussed in the final section, where remaining challenges in the field are also identified. It is believed that this review will guide material researchers in their future work of developing smart biosensors, which can further improve detection sensitivity in monitoring currently known and future virus threats.

Breath analysis for detection of viral infection, the current position of the field.

The COVID-19 pandemic has highlighted the importance of rapid, cost effective, accurate, and non-invasive testing for viral infections. Volatile compounds (VCs) have been suggested for several decades as fulfilling these criteria. However currently very little work has been done in trying to diagnose viral infections using VCs. Much of the work carried out to date involves the differentiation of bacterial and viral sources of infection and often the detection of bacterial and viral co-infection. However, this has usually been done in vitro and very little work has involved the use of human participants. Viruses hijack the host cell metabolism and do not produce their own metabolites so identifying virus specific VCs is at best a challenging task. However, there are proteins and lipids that are potential candidates as markers of viral infection. The current understanding is that host cell glycolysis is upregulated under viral infection to increase the available energy for viral replication. There is some evidence that viral infection leads to the increase of production of fatty acids, alkanes, and alkanes related products. For instance, 2,3-butandione, aldehydes, 2,8-dimethyl-undecane and n-propyl acetate have all been correlated with viral infection. Currently, the literature points to markers of oxidative stress (e.g. nitric oxide, aldehydes etc) being the most useful in the determination of viral infection. The issue, however, is that there are also many other conditions that can lead to oxidative stress markers being produced. In this review a range of (mainly mass spectrometric) methods are discussed for viral detection in breath, including breath condensate. Currently MALDI-ToF-MS is likely to be the preferred method for the identification of viral strains and variants of those strains, however it is limited by its need for the viral strains to have been sequenced and logged in a database.