Emergency Hepatitis B Treatment
See your GP as soon as possible if you think you may have been exposed to the hepatitis B virus.
To help stop you becoming infected, they can give you:
- a dose of the hepatitis B vaccine you’ll also need 2 further doses over the next few months to give you long-term protection
- hepatitis B immunoglobulin a preparation of antibodies that work against the hepatitis B virus and can offer immediate but short-term protection until the vaccine starts to take effect
These are most effective if given within 48 hours after possible exposure to hepatitis B, but you can still have them up to a week after exposure.
Molecular Diagnosis Of Drug
The molecular diagnosis of drug-resistant HBV is performed by genotypic assay, which determines the resistance-related mutations in the viral RT gene by comparing the patient-derived viral strain with wild-type. To date, several methods have been developed and clinically used to determine genotypic resistance. These methods include sequencing , restriction fragment length or mass polymorphism , and hybridization . Since the conventional methods for HBV genotyping have been extensively reviewed in literature, only those technologies that have received lesser attention elsewhere, such as ultra-deep pyrosequencing and RFMP, will be reviewed here in detail.
How Common Is Hepatitis B
The number of people who get this disease is down, the CDC says. Rates have dropped from an average of 200,000 per year in the 1980s to around 20,000 in 2016. People between the ages of 20 and 49 are most likely to get it.
About 90% of infants and 25-50% of children between the ages of 1-5 will become chronically infected. In adults, approximately 95% will recover completely and will not go on to have a chronic infection.
As many as 1.2 million people in the U.S. are carriers of the virus.
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Agents For Influenza A And Respiratory Viruses
- These agents are used to treat the signs and symptoms of respiratory flu caused by influenza A and B viruses as well as respiratory syncytial viruses . While vaccines are available, drug therapy would be the best option if patients manifest the viral infection and spontaneous resolution does not occur.
Characteristics Of Nanoparticle Drug Delivery Systems For Anti
Nanoparticle drug delivery systems refer to drug preparations with particle sizes ranging from 1 nm to 1000 nm. The particle size, potential, morphology, and internal structure of the nanoparticle drug delivery system are controllable. Several nanoparticle drug delivery systems with specific biochemical characteristics have been designed to achieve personalized and targeted treatment. Nanoparticle drug delivery systems have significant advantages in the treatment of hepatitis B infection. These include the ability to passively target the liver tissue through hepatic macrophages , be modified with hepatocyte-targeting molecules to achieve active distribution of the drug in the liver, achieve environment-responsive drug release by bonding environment-sensitive ligands based on the intracellular environment of liver cells, and encapsulate a variety of drug molecules simultaneously, thereby achieving codelivery of multiple therapeutic drugs with different efficacies.
Liver-targeting process of nanoparticle drug delivery system. Reproduced from Nanotoday 2010, 5, 296312.
- Controlling the particle size below 200 nm, which reduces phagocytosis by nonparenchymal cells such as Kupffer cells, and further controlling the particle size at 50100 nm, which is conducive to uptake by the hepatocytes.
- Modification of the nanoparticle delivery system to achieve targeted uptake by hepatocytes .
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Virion Structure And Genome
HBV particles, also known as Dane particles , were firstly identified by Dane and colleagues in 1970 . Their shape is spherical, with a diameter of â¼42 nm. They consist of an outer envelope, which is a host-derived lipid bilayer containing three different-sized HBV surface antigens âlarge , middle and small âsurrounding the viral nucleocapsid. The nucleocapsid is icosahedral and comprises the HBV core protein , as well as the viral DNA genome and the viral DNA polymerase . The virus also secretes a wide range of defective particles , including enveloped nucleocapsids that are empty or contain defective immature genomes and subviral lipid particles containing the viral surface antigens. The subviral particles are secreted along with the infectious virions at levels that are thousands of times higher, and they play an important role in suppressing antibody responses to the virus .
Hepatitis B Virus particles. Infectious HBV virion . The lipid envelope, bearing three types of surface proteinsâsmall , middle and large âsurrounds the nucleocapsid, consisting of HBV relaxed circular DNA , the viral DNA polymerase , and the core protein . Non-infectious HBV particles enveloped nucleocapsids containing immature or defective DNA/RNA, subviral particles, and naked nucleocapsids.
Hepatitis B Virus genome. Partially double-stranded, relaxed circular DNA with four overlapping open reading frames .
Blood Products And Intravenous Immunoglobulin
Transfusion of blood products or infusion of intravenous immunoglobulin can result in passive transmission of antibodies associated with HBV. This can lead to patients being falsely informed that there is evidence of past HBV or, more importantly, being considered for antiviral prophylaxis in the context of immunosuppression. Baseline anti-HBc should be measured early during the course of disease to avoid this scenario and, if negative, subsequent positive serology can be disregarded in the absence of ongoing risk of acquisition of HBV. Should liver function tests become deranged during the course of immune suppression, HBsAg should be retested, as in any other patient.
Tropomyosin Chain Supports Extracellular Hepatitis B Virus Production
Figure 5 Tropomyosin chain knockdown decreases hepatitis B virus production. TPM2 mRNA in maoto-treated cells. HepG2-NTCP cells were treated with distilled water or concentrations of 1.5625, 6.25, 25, and 100 µg/ml of maoto extract for 9 days. The amount of TPM2 mRNA was measured by real-time RT-PCR. Schematic representation of the protocol of maoto treatment and transfection of an HBV-expressing plasmid together with an sh-TPM2-expressing plasmid in HepG2 cells. The remaining plasmids were washed at 6 h after the transfection and the medium was refreshed . The medium was further refreshed at 3 days after the transfection . TPM2 mRNA in sh-TPM2-expressing cells. Knockdown of TPM2 was confirmed at 7 days after the transfection by real-time RT-PCR. Effect of TPM2 knockdown on HBV production. HBV DNA in culture supernatants of the cells was measured by real-time PCR and normalized with the transfection efficiency based on luciferase activity of the cells. Lamivudine was used as a positive control for the inhibition of HBV production. Effect of maoto extract on HBV production in sh-TPM2-expressing cells. Values are expressed as the mean percentage + S.E. of three independent experiments. *P< 0.05 **P< 0.01 ****P< 0.001 N.S., no significance.
Approaches By Virus Life Cycle Stage
Viruses consist of a genome and sometimes a few enzymes stored in a capsule made of protein , and sometimes covered with a lipid layer . Viruses cannot reproduce on their own and instead propagate by subjugating a host cell to produce copies of themselves, thus producing the next generation.
Researchers working on such “rational drug design” strategies for developing antivirals have tried to attack viruses at every stage of their life cycles. Some species of mushrooms have been found to contain multiple antiviral chemicals with similar synergistic effects.Compounds isolated from fruiting bodies and filtrates of various mushrooms have broad-spectrum antiviral activities, but successful production and availability of such compounds as frontline antiviral is a long way away. Viral life cycles vary in their precise details depending on the type of virus, but they all share a general pattern:
Before cell entry
This stage of viral replication can be inhibited in two ways:
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Nucleocapsid Assembly Inhibitors Or Modulators
The HBV core particle is actively involved in the HBV replication cycle. It is required for the transfer of the viral genome to and from the nucleus of the infected hepatocyte, as well as for a successful reverse transcription . Thus, it is a promising target for antiviral drugs . New regulators or inhibitors of nucleocapsid assembly can affect various stages of the HBV replication cycle, including capsid formation, reverse transcription, and pgRNA encapsidation . Based on the three-dimensional structure of capsids when they interact with a ligand, two categories of analogues have been developed .
Both classes of CpAMs inhibit the release of viral particles. Thus, the amount of HBV DNA and RNA leaving the hepatocyte is reduced. They also prevent de novo cccDNA formation due to blocking the formation of functional capsids, and hence viral replication . The structures of the abovementioned compounds are shown in .
Nucleocapsid assembly modulators or inhibitors .
Treatment Options For Antiviral Resistant Pathogens
If a virus is not fully wiped out during a regimen of antivirals, treatment creates a bottleneck in the viral population that selects for resistance, and there is a chance that a resistant strain may repopulate the host. Viral treatment mechanisms must therefore account for the selection of resistant viruses.
The most commonly used method for treating resistant viruses is combination therapy, which uses multiple antivirals in one treatment regimen. This is thought to decrease the likelihood that one mutation could cause antiviral resistance, as the antivirals in the cocktail target different stages of the viral life cycle. This is frequently used in retroviruses like HIV, but a number of studies have demonstrated its effectiveness against influenza A, as well. Viruses can also be screened for resistance to drugs before treatment is started. This minimizes exposure to unnecessary antivirals and ensures that an effective medication is being used. This may improve patient outcomes and could help detect new resistance mutations during routine scanning for known mutants. However, this has not been consistently implemented in treatment facilities at this time.
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Transient Hepatitis B Virus Production
HepG2 cells were cotransfected with pHBI together with pGL3 to normalize the transfection efficiency and an shRNA-expressing plasmid using GenJet In Vitro DNA Transfection Reagent according to the manufacturers instructions. At 7 days post-transfection, the culture supernatant was used to measure the level of HBV production by real-time PCR, and cell lysates were used to check the transfection efficiency by a Luciferase Assay System .
Toward A Cure Of Hbv Infection With Novel Combination Strategies
One of the major questions regarding antiviral therapy of CHB was whether the combination of Peg-IFN- with NAs could improve the off-treatment response rate and the rate of HBsAg seroconversion to shorten treatment duration. However, despite the observation that the combination of Peg-IFN- with LMV or LdT showed a higher on-treatment virological response, it did not show a higher rate of sustained off-treatment virological or serological response . Several studies are ongoing with the combination of Peg-IFN- and ETV or TFV , but, presently, this type of combination is not yet recommended. Furthermore, there are no data to indicate an advantage of de novo combination with ETV and TFV in NA-naïve patients, although more studies in patients with high baseline viremia are required.
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Practice Quiz: Antiviral Drugs
1. A 15 y/o patient came in for a severe case of respiratory flu and would need drug therapy. Which of the following drugs should the nurse anticipate to be prescribed?
1. Answer: B. amantadine .
- It is indicated for respiratory viruses.
- Options A and D are for herpes viruses and CMV
- Option C is an NRTI and is indicated for HIV and AIDS.
2. Which of the following antiviral agents is effective as treatment for H1N1?
A. zidovudineC. oseltamivirD. Selzentry
2. Answer: C. oseltamivir. It is the only antiviral agent effective for H1N1 and avian flu.
- Option A is the only antiviral agent allowed for use in pregnant women.
- Option B is the drug of choice for herpes and CMV infections in children.
- Lastly, option D is a brand name of maraviroc, a CCR5 coreceptor antagonist of HIV virus.
3. A student nurse administering acyclovir was asked by the clinical instructor on how the drug works. The student nurse would be correct by stating that this drug works in which way?
A. unknown but it is believed to be shedding the protein coat of the virus.B. it competes with viral receptors found in the host cellsC. it takes away the necessary substances needed by viruses to form DNA chainsD. trapping the viruses and disintegrating them directly
3. Answer: C. it takes away the necessary substances needed by viruses to form DNA chains.
Maoto Suppresses Extracellular Hepatitis B Virus Production In Hepad387 Cells
To confirm the effect of maoto, we evaluated it in HepAD38.7 cells in more detail . We first confirmed that the maoto extract did not show any cytotoxicity at a concentration of 100 µg/ml . Then, the effect of maoto on HBV production was evaluated at various concentrations under 100 µg/ml . Consistent with the results in Figure 1C, maoto inhibited extracellular HBV production in HepAD38.7 cells in a dose-dependent manner . Maoto did not affect HBeAg production, which is thought to correlate with HBV pgRNA production, in the tested concentration range . These results confirmed the inhibitory effect of maoto on extracellular HBV production without any cytotoxicity and suggest that maoto inhibits a step in the HBV production process after HBV pgRNA expression.
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Nonnucleoside Reverse Transcriptase Inhibitors
- This antiretroviral drug has direct effects on HIV activities within the cell.
The desired and beneficial action of this antiretroviral drug is:
- Binding directly to HIV reverse transcriptase to block both RNA- and DNA-dependent DNA polymerase activities. They prevent the transfer of information that would allow the virus to carry on the formation of viral DNA. Consequently, replication becomes impossible.
Nonnuceloside reverse transcriptase inhibitors are indicated for the following medical conditions:
- Treatment of patients with documented AIDS or ARC who have decreased numbers of helper T cells and evidence of increased opportunistic infections in combination with other antiviral drugs.
Here are the characteristic interactions of nonnucleoside reverse transcriptase inhibitors and the body in terms of absorption, distribution, metabolism, and excretion:
Contraindications and Cautions
The following are contraindications and cautions for the use of nonnucleoside reverse transcriptase inhibitors:
- Pregnancy. No adequate studies of nonnucleoside reverse transcriptase inhibitors so use should be limited only in which benefits clearly outweigh any risks.
- Children. Safety for the use of delavirdine is not established.
Use of nonnucleoside reverse transcriptase inhibitors may result to these adverse effects:
Treatment Options For Hepatitis B
People living with chronic hepatitis B infection should expect to live a long and healthy life. There are decisions people can make to protect their livers such as seeing a liver specialist or health care provider regularly, avoiding alcohol and tobacco, and eating healthy foods. There are also approved drugs for both adults and children that control the hepatitis B virus, which helps reduce the risk of developing more serious liver disease, but there is still no complete cure.
Current treatments for hepatitis B fall into two general categories:
- Immune modulator Drugs These are interferon-type drugs that boost the immune system to help get rid of the hepatitis B virus. They are given as a shot over 6 months to 1 year.
- Antiviral Drugs These are drugs that stop or slow down the hepatitis B virus from reproducing, which reduces the inflammation and damage of your liver. These are taken as a pill once a day for at least 1 year and usually longer.
It is important to know that not everyone with chronic hepatitis B infection needs to be treated. This can be difficult to accept when first diagnosed because taking a drug to get rid of the virus seems like the first step to getting better. Current treatments, however, are generally found to be most effective in those who show signs of active liver disease .
Hepatitis B Drug Watch
Visit the HBF Drug Watch for a complete list of the approved treatments for hepatitis B and promising new drugs in development.
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Management Of Treatment Failure
Assessment of Treatment Adherence
Good adherence to anti-HBV therapies is important for maintaining maximal suppression of HBV replication . Poor adherence can result in substantially reduced plasma drug levels, depending on the number of doses missed and the half-life of the drug, and can result in increased viral replication . Investigation of adherence to NA therapy in patients with CHB has shown that nearly 40% may not be fully adherent this significantly impacts on the rates of viral suppression . Low-level viral replication associated with nonadherence increases the pressure on the potency of the NA, and consequently increases the risk of selecting for resistance. Specific treatment adherence questionnaires and drug concentration monitoring can be useful for the management of patients. The level of education, type of health insurance, cultural factors, as well as low copayment for medications can significantly impact medication adherence. Thus, programs on patient counseling and on medication adherence to improve effectiveness of antiviral therapy in clinical practice are recommended.
Management of treatment failure
Treatment Adaptation According to Cross-Resistance
Management of Antiviral Drug Resistance