What Should Be The Focus For The Next 10 Years Where Should Efforts And Money Be Invested To Achieve The Elimination Goals
F.Z. There is a chronic lack of funding for hepatitis programmes worldwide. We need to increase general public awareness of the substantial disease burden of viral hepatitis to better leverage funding amongst key stakeholders. This step will aid in the implementation of public health programmes with the aim of eliminating viral hepatitis. There is important synergy within the screening, prevention and treatment programmes for HIV, sexually transmitted diseases and viral hepatitis. We should use this synergy to our advantage to increase funding for viral hepatitis. Specific actions should be undertaken to develop and provide affordable, easy-to-use and rapid point-of-care tests to implement test-and-treat strategies for all hepatitis viruses and HIV.
For HCV, the high-risks groups are those who are more difficult to reach. Programmes to develop harm-reduction services and facilitate access to treatment for intravenous drug users should be prioritized, as well as programmes for other high-risk populations such as those that are incarcerated or migrants, for instance. For HBV, programmes to provide timely doses of HBV vaccine at birth in Africa and other highly endemic regions are urgently needed. As most of the HBV-infected patients live in resource-poor locations, there is an urgent need to expand access to diagnosis, treatment and cure. As HBV is the main cause of HCC, HCC screening programmes should be implemented in those infected with HBV.
Hbv Burden In Cld/hcc
Alcohol is presently the most common aetiology of CLD in India, and this representation has emerged over a span of the last few years . Interestingly, this is due to rising alcohol consumption rates and not due to a real decrease in prevalence of HBV infection nor the effect of vaccination . However, HBV infection still remains the most common aetiology of HCC all over India. A recent all-India survey revealed that 43% of HCC cases are HBV-associated prevalence among HCC cases is 42% in the south, 3969% in the north and 82% in the west.
Trends in aetiology of chronic liver disease in north, west, south and east India.
Eqhbv And Hbv Infect Horse
Because cross-species transmission can occur in hepadnaviruses and because host genetic relatedness may facilitate CST , we investigated whether horse-derived primary equine hepatocytes are susceptible to EqHBV. Expression and physiological functionality of the NTCP ortholog in PEHs was confirmed by IFA using a cross-reactive NTCP-antibody and a taurocholate transport assay . PEHs were susceptible to both HDVHBV and HDVZe-EqHBV, but not to HDVDo-EqHBV , potentially associated with 10 amino acid residues differing between donkey- and the zebra-associated EqHBV strains within the ORF encoding the viral surface proteins likely mediating entry . To further analyze the ability of human HBV to replicate in PEHs, we used cell culture-derived infectious HBV particles. Successful infection was demonstrated by de novo HBeAg production characteristic for HBV infection . Productive HBV infection could be inhibited by vaccine-derived anti-HBs antibodies , but not by a high-titered EqHBV antibody+ donkey serum , compatible with antigenic divergence of HBV and EqHBV surface proteins. Infection of PEHs with EqHBV+ sera from donkeys or zebras was not observed, potentially due to degradation after long-term storage and sampling in tropical settings and due to limited sample volumes preventing generation of high-titered inocula .
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Is Elimination Of Viral Hepatitis By 2030 Feasible
Andrea L. Cox. Hepatitis B virus and hepatitis C virus combined are among the top four global infectious disease killers alongside tuberculosis, malaria and HIV. Although the number of people in the world dying from HIV, tuberculosis and malaria have all declined since 2008, global deaths from chronic HBV and HCV infection continue to rise, with more than 1.4 million deaths each year. Globally, HBV-related liver disease represents the seventh highest cause of mortality worldwide. Given this burden, viral hepatitis elimination should be a priority. However, available evidence demonstrates that global viral hepatitis elimination by 2030 is highly unlikely. Rates of hepatitis B and C diagnosis are very low, averaging 8% and 18%, respectively, globally. Although some regions are approaching prophylaxis and prevalence targets for HBV infection, studies suggest that all regions must substantially scale up rates of diagnosis and access to treatment to meet the global targets,,. For HCV infection, 80% of high-income countries are not on track to meet HCV elimination targets by 2030, and 67% will not meet elimination targets even if given an additional 20 years to do so. Elimination is even less likely in most low-income and middle-income countries . In contrast to HBV, there is no prophylactic HCV vaccine. Thus, it is not surprising that the WHO incidence reduction targets are the most difficult to achieve for hepatitis C.
Sensitivity And Specificity Of Commercially Available Rapid Diagnostic Tests For Viral Hepatitis B And C Screening In Serum Samples
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Contributed equally to this work with: Ganbolor Jargalsaikhan, Miriam Eichner
Roles Data curation, Project administration, Supervision, Writing original draft
Affiliations Liver Center, Sukhbaatar District, Ulaanbaatar, Mongolia, Onom Foundation, Khan-Uul District, Ulaanbaatar, Mongolia
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Contributed equally to this work with: Ganbolor Jargalsaikhan, Miriam Eichner
Roles Formal analysis, Methodology, Writing original draft, Writing review & editing
Affiliations Liver Center, Sukhbaatar District, Ulaanbaatar, Mongolia, Onom Foundation, Khan-Uul District, Ulaanbaatar, Mongolia
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Hbsag Clearance After Na Treatment
There are few large or conclusive studies on the clearance of HBsAg after NA treatment, and some of these studies are single-centre retrospective studies. Kim et al. reported a clearance rate of 1% or less in 110 CHB patients who were treated with ETV/LAM for approximately 1 year. A retrospective study by Yip et al. reported an HBsAg clearance rate of 2.1% after an average follow-up of 4.8 years in 20,263 CHB patients treated with ETV/TDF for longer than 6 months. Wong et al. retrospectively evaluated 1072 CHB patients on antiviral therapy for approximately 6 years and found an HBsAg clearance rate of 4.58%. This study found no significant difference in the clearance rate between HBeAg-positive and HBeAg-negative patients, but the rate in patients with cirrhosis was significantly lower than patients without cirrhosis . These results suggested that the clearance rate of non-cirrhosis patients was higher after NA treatment, which is not consistent with the results of patients who experienced spontaneous clearance. Compared to patients with normal baseline ALT, patients with higher ALT levels had significantly higher rates of achieving HBsAg clearance. In general, the clearance rate may increase with the extension of treatment in CHB patients, but the overall rate with currently available NA treatment is low. The HBsAg clearance rates were 1.45.1% after an average follow-up of 27 years after NA treatment .
Progress In Treatment And Cure
Many countries are demonstrating strong political leadership, facilitating dramatic price reductions in hepatitis medicines, including through the use of generic medicineswhich allow better access for more people within a short time.
In 2016, 1.76 million people were newly treated for hepatitis C , a significant increase on the 1.1 million people who were treated in 2015. The 2.8 million additional people starting lifelong treatment for hepatitis B in 2016 was a marked increase from the 1.7 million people starting it in 2015. But these milestones represent only initial steps access to treatment must be increased globally if the 80% treatment target is to be reached by 2030.
However, funding remains a major constraint: most countries lack adequate financial resources to fund key hepatitis services.
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Hepatitis B During Pregnancy
If a woman with HBV becomes pregnant, they may transmit the virus to their baby. Women should inform the doctor who delivers their baby that they have HBV.
The infant should receive an HBV vaccine and HBIG with 1224 hours of birth. This significantly reduces the risk that they will develop HBV.
The HBV vaccine is safe to receive while pregnant.
People with a high risk of HBV include:
- the infants of mothers with HBV
- the sexual partners of people with HBV
- people who engage in sexual intercourse without contraception and those who have multiple sexual partners
- men who have sex with men
- people who inject illicit drugs
- those who share a household with a person who has a chronic HBV infection
- healthcare and public safety workers who are at risk of occupational exposure to blood or contaminated bodily fluids
- people receiving hemodialysis, which is a type of kidney treatment
- people taking medications that suppress the immune system, such as chemotherapy for cancer
- those who come from a region with a high incidence of HBV
- all women during pregnancy
People can prevent HBV infection by:
- wearing appropriate protective equipment when working in healthcare settings or dealing with medical emergencies
- not sharing needles
- following safe sexual practices
- cleaning any blood spills or dried blood with gloved hands using a 1:10 dilution of one part household bleach to 10 parts water
A vaccine against HBV has been available since 1982.
People who should receive this vaccine include:
Tenofovir Reduces Severity Of Covid
Encouraging data from a new study found that antiretroviral drug, tenofovir, prevented serious COVID-19 illness amongst people living with chronic Hepatitis B.
A study conducted in Spain found that antiretrovira drug tenofovir reduced the severity of COVID-19 in patients with chronic Hepatitis B.Beatriz Mateos Muñoz, PhD Specialist in Gastroenterology and Hepatology at the Hospital Universitario Ramón in Spain, said the study analysed data from 4736 patients from 28 Spanish hospitals.
Of the 117 COVID-19 positive patients who were identified, 67 were taking tenofovir and 50 were on entecavir, an antiviral drug in the treatment of hepatitis B virus infection. Muñoz said the incidence of COVID-19 in patients on tenofovir or entecavir were similar, but that patients on entecavir more often had severe COVID-19, required ICU, ventilatory support, had longer hospitalization or died.
The study found that tenofovir seemed to offer some protection in patients with chronic hepatitis B infected by COVID-19.
In multivariate logistic regression adjusted by age, sex, obesity, comorbidities and fibrosis stage, tenofovir reduced by 6-fold the risk of severe COVID-19. Patients with chronic hepatitis B on tenofovir have a lower risk of severe COVID-19 infection than those on entecavir.
This is an excerpt from the article Leading Researchers Highlight the Impact of COVID-19 on Global Liver Disease on Health Policy Watch. Read more here.
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Frequency Of Immune Cell Subsets Is Independent Of Serum Hbsag Levels
To determine if CHB patients with varying level of serum HBsAg have differential phenotypic attributes of immune cell subsets, frequencies of T cells, B cells , monocytes, NK cells and Tregs were compared between the patients with HBsAg< 500IU/ml and HBsAg> 50,000IU/ml . Healthy donors were included as reference. No differences in the proportion of total T cells, CD4+ and CD8+ T cells, B cells , monocytes, NK cells and Tregs were found among the HBshi, HBslo and HD groups. Further analysis of memory T cell subsets based on CCR7 and CD45RO expression showed no significant difference in the proportions of the naïve, central memory , effector memory or terminally differentiated effector T cells between the HBshi and HBslo groups . However, CM CD4+ T cells increased significantly in both groups compared to HD, along with a proportional decrease in the naive subset . In contrast, the proportions of the naïve and CM CD8+ T cell subsets were similar among the groups . Analysis of memory B cell subset based on CD21 and CD27 expression also showed no difference in the proportion of the naïve, resting memory , active memory and atypical memory cell subsets between HBshi and HBslo groups . Only naïve B cell subset of HBshi were lower than those of HD. These data indicate that serum HBsAg levels had minimal impact on the global immune cell composition.
Figure 1
A Divergent Hepadnavirus Species In Donkeys And Zebras
Phylogeny and epidemiology of EqHBV. Organization of HBV and EqHBV genomes. Complete genome-based maximum-likelihood phylogeny. Immunofluorescence costaining using an anti-EqHBV antibody+ donkey serum and a rabbit anti-HBc serum. EqHBV DNA and antibody detection in donkeys and zebras. Seroprevalence per country , sex , and age group . Ab, antibodies EqHBV, Equid HBV EqHCV, Equid HCV S, surface protein Pol, polymerase HBx, hepatitis B virus X protein.
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Global Epidemiology Of Hepatitis B
Hepatitis B virus is a virus containing a DNA genome of 3226 base pairs that can cause a potentially life-threatening liver infection. About 2 billion people have been infected with HBV worldwide of which, 350 million are in chronic infection status. HBV is one of the most frequently identied pathogens that lead to acute and chronic hepatitis, acute liver failure and death in East Asia. Three quarters of the HBV carries reside in the Asia-Pacic region. Nevertheless, northern, western and central Europe, North America and Australia are among the lowest prevalence area of chronic HBV infection and HBV exposure , while Eastern Europe, the Mediterranean, Russia, Southwest Asia and Central and South America have higher prevalence rates . Southeast Asia, China and tropical Africa have the highest prevalence rates .
Patients infected with HBV, either chronic or resolved HBV infection cases, are at risk of HBV reactivation when they undergo chemotherapy. HBVr could occur in patients receiving chemotherapy for hematological malignancies or hematopoietic stem cell transplantation recipients as well as patients receiving treatment for solid tumors such as breast cancer. In HBsAg-positive lymphoma patients undergoing rituximab plus steroid combination chemotherapy and HSCT, HBVr rates could be up to 24% to 88%. Increasingly, patients with solid tumors receiving chemotherapy, particularly in breast cancer patients receiving anthracycline-based regimens, are also at risk of HBVr.
Checkpoint Blockade Improves Hbsag
It is possible that similar with HBV-specific T cell responses, B cell function in CHB patients may also be dysregulated in a HBsAg level-dependent manner. However, the number of HBsAg-specific as well as total IgG antibody-secreting cells detected by ELISpot assay following in vitro polyclonal stimulation were not different between the HBslo and HBshi groups . In addition, the fold changes in HBsAg-specific as well as total IgG ASC responses by PD1/PD-L1 blockade using PD-1 were not different between the two groups. Similar with total IFN T cell responses to checkpoint blockade, it was possible that the sensitivity of B cell response to checkpoint blockade may require much lower serum HBsAg levels than the defined low value of the current study. To this end, HBsAg-specific ASC responses to PD-1 were compared between patients with HBsAg< 100IU/ml and with > 5,000IU/ml . Interestingly, patients with HBsAg< 100IU/ml group showed significantly higher fold change in HBsAg-specific IgG ASCs than those with HBsAg> 5,000IU/ml . The patients with HBsAg< 100IU/ml also showed higher number of responders than those with HBsAg> 5,000IU/ml . Therefore, while HBsAg-specific ASC responses were detectable in all CHB patients regardless of serum HBsAg levels, serum HBsAg levels < 100IU/mL may represent a cutoff that differentiates B cells plasticity to checkpoint modulation among CHB patients.
Figure 5
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Accessibility And Hbsag Clearance Rate
HBsAg clearance occurs spontaneously or via antiviral treatment in CHB patients. The most commonly used drugs are nucleoside analogue and pegylated interferon . NA drugs include entecavir , tenofovir disoproxil fumarate and tenofovir alafenamide fumarate . The 2018 AASLD guidelines recommend Peg-IFN, ETV, or TDF as the preferred initial therapy for adults with immune-active CHB. It also suggests that alanine transaminase levels be tested at least every 6 months for adults with immune-tolerant CHB to monitor for potential transition to immune-active or immune-inactive CHB . The 2017 EASL guideline recommends ETV, TDF and TAF as the preferred monotherapy regimens, and the extension of the duration of Peg-IFN therapy beyond week 48 may be beneficial in selected HBeAg-negative CHB patients . The potential side effects of NAs include lactic acidosis for ETV and nephropathy, osteomalacia, lactic acidosis for TDF. CHB patients should be clinically monitored. The most frequently reported side effects for Peg-IFN are flu-like syndrome, myalgia, fatigue, mood disturbances, weight loss, hair loss and local reactions at the site of injection, and these side effects may be partially managed with dose reduction . Currently, the clearance of HBsAg is based primarily on sequential or combined treatment with NA and Peg-IFN.
Zebras And Donkeys Have Antibodies Against Hepadnaviruses
To elucidate the geographic distribution of EqHBV and to test whether EqHBV elicits an adaptive immune response, we performed an immunofluorescence assay relying on the antigenically conserved HBV core protein for antibody detection . The serological reactivity pattern of donkey sera was dispersed across both cytoplasm and nucleus, resembling human anti-HBc antibody reactivity . Anti-HBV antibodies were detected in 5.4% of donkey and zebra sera originating from almost all sampled countries , suggesting a worldwide distribution of EqHBV. Consistent with the absence of positive results during PCR testing, 150 horses sampled in Germany, Spain, and Brazil showed no evidence for HBV antibodies in the same IFA . The overall EqHBV seroprevalence in donkeys and zebras was low compared to about 20% HBV antibody prevalence in nonvaccinated human populations or in nonhuman primates . However, similarly low seroprevalence rates occur in other nonprimate hepadnavirus hosts, such as bats and shrews with 1.2 to 3.4% , suggesting robustness of serological testing and commonalities of HBV spread in nonprimate hosts. Notably, the total EqHBV seroprevalence closely corresponded to the EqHBV DNA detection rate by PCR, suggesting uncommon abortive infection or spontaneous virus clearance.
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Hepatitis B Foundation Applauds Fda Approval Of New Hepatitis B Vaccine
FDA Approved HEPLISAV-B, the First New Hepatitis B Vaccine in More than 25 Years
DOYLESTOWN, PA : Today on World Immunization Day, the Hepatitis B Foundation applauded the U.S. Food and Drug Administrations approval of HEPLISAV-B, the first new hepatitis B vaccine in more than 25 years and the only two-dose schedule for the prevention of infection in adults.
Hepatitis B is an extremely infectious virus , and it is the most common serious liver infection in the world. More than 257 million people worldwide and up to 2.2 million in the United States are chronically infected with hepatitis B. Each year up to 1 million people die from HBV despite the fact that it is preventable and treatable.
The new two-dose vaccine is a game changer, said Timothy Block, PhD, president of the Hepatitis B Foundation. Current vaccines require three doses over 6 months, which makes it hard for some people to get all doses. With the new vaccine, people can be fully protected with two doses, in just one month. As we work towards finding a cure and eliminating hepatitis B in the U.S. and globally, having this new tool in our arsenal will play a critical role in preventing infections.
In addition, for the first time since 2006, the number of reported cases of acute HBV infection across the country is rising, and increased by 20.7% in 2015 alone. Parts of the country that are hardest hit by the opioid epidemic are now facing a rise in acute HBV infection associated with injection drug use.
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