Integration Of Hepatitis B Virus Dna
It has been long recognized that most tumors in HBV associated HCC contain clonally integrated HBV DNA and microdeletions in the flanking cellular DNA which could deregulate cellular growth control mechanisms . Indeed, in HCCs developed in woodchucks infected with woodchuck hepatitis B virus , WHV DNA insertions predominantly occur in the N-myc2 oncogene which leads to N-myc2 activation . Recent studies of HBV insertions in HBV-related HCCs revealed that also HBV integration can occur in genes that target telomerase and mixed lineage leukemia encoding genes suggesting potentially common pathways in HBV-related carcinogenesis . HBV DNA integration has also been observed in patients with chronic hepatitis suggesting that integration is likely an early step in the process of hepatocarcinogenesis . However, HBV integration is not likely occur in resting hepatocytes. Thus, if integration of the HBV genome contributes to hepatocarcinogenesis, it is likely to be secondary to procarcinogenic events that trigger hepatocyte turnover as described below.
Inhibitors Of Reverse Transcriptase
Although viruses become parts of their host cell during their life cycle, basic research on their replication mechanisms identified various virus-specific biochemical pathways that could be targets of pharmaceutical intervention. The nucleoside analogue acyclovir against herpes simplex and varicella zoster virus was the first example of a successful nontoxic antiviral drug taylored to the biochemistry of its viral target. Merigan and Robinson turned in the late 1970s to then available inhibitors of DNA polymerases when they realised that interferon alone would not help the majority of patients. However, these early drugs, though effective, were highly toxic, in particular to the mitochondrial DNA polymerase . With the advent of HIV in the developed countries, research on antiviral therapy got a strong boost leading to the first drug azidothymidine in 1987 which inhibited more specifically the reverse transcriptase of HIV, but it was unfortunately inactive against HBV.
Hbv Dna In Hepatoma Cells
While the immunopathogenesis of HBV is relatively well understood, the mechanisms of oncogenicity are not. Early hopes that explantation and cultivation of hepatoma cells from HBV carriers would lead to a culture system for HBV were not fulfilled because the cells usually did not express HBV antigens or HBV DNA. However, in 1976 South-African researcher Jennifer Alexander was able to establish the hepatoma cell line PLC PRF 5 which secreted HBsAg . Shortly thereafter the team of William Rutter identified several fragments of HBV DNA integrated at several chromosomal sites in that cell line .
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How Is It Spread
Hepatitis A is spread when a person ingests fecal mattereven in microscopic amountsfrom contact with objects, food, or drinks contaminated by feces or stool from an infected person.
Hepatitis B is primarily spread when blood, semen, or certain other body fluids- even in microscopic amounts from a person infected with the hepatitis B virus enters the body of someone who is not infected. The hepatitis B virus can also be transmitted from:
- Birth to an infected mother
- Sex with an infected person
- Sharing equipment that has been contaminated with blood from an infected person, such as needles, syringes, and even medical equipment, such as glucose monitors
- Sharing personal items such as toothbrushes or razors
- Poor infection control has resulted in outbreaks in health care facilities
Hepatitis C is spread when blood from a person infected with the Hepatitis C virus even in microscopic amounts enters the body of someone who is not infected. The hepatitis C virus can also be transmitted from:
- Sharing equipment that has been contaminated with blood from an infected person, such as needles and syringes
- Receiving a blood transfusion or organ transplant before 1992
- Poor infection control has resulted in outbreaks in health care facilities
- Birth to an infected mother
Treatment For Chronic Hbv Infection
For chronic HBV infection, antiviral medications are available.
This is not a cure for chronic HBV. However, it can stop the virus from replicating and prevent its progression into advanced liver disease.
A person with a chronic HBV infection can develop cirrhosis or liver cancer rapidly and without warning. If a person does not have access to adequate treatment or facilities, liver cancer can be fatal within months of diagnosis.
People with a chronic HBV infection require ongoing medical evaluation and an ultrasound of the liver
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How Is Hepatitis B Spread
You can become infected with hepatitis B through exposure to blood, semen and other bodily fluids of an infected person. You can get the infection by:
- Having unprotected sex.
- Sharing or using dirty needles for drug use, tattoos or piercing.
- Sharing everyday items that may contain body fluids, including razors, toothbrushes, jewelry for piercings and nail clippers.
- Being treated medically by someone who does not use sterile instruments.
- Being bitten by someone with the infection.
- Being born to a pregnant woman with the infection.
Hepatitis B is not spread by:
- Kissing on the cheek or lips.
- Coughing or sneezing.
- Hugging, shaking hands or holding hands.
- Eating food that someone with the infection has prepared.
What Laboratory Tests Are Available For Hepatitis B
Tests are available to detect the types of antigens used to identify the hepatitis B virus. The tests determine if the virus is present in the body tissue or blood. The amount of each type of antigen present indicates how advanced the disease is and how infective the individual has become.
Other tests are available to detect the body’s reaction to the viral infection or the body’s reaction to vaccination against the virus. These tests work by measuring the number of antibodies present in the blood.
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What Occupations Have Increased Risk Of Hepatitis B
In general, occupational groups with increased risk include:
- Health-care workers repeatedly exposed to blood or blood products or those who are at risk of needlestick injury.
- Pathologists, laboratory personnel, or embalmers.
- Dentists, dental assistants, and dental hygienists.
- Certain staff members of institutions for the developmentally handicapped.
- Staff of institutions where workers may be exposed to aggressive, biting residents.
Travellers to regions with intermediate or high rates of endemic HBV infection may also consider being vaccinated.
Prevention Of Hepatitis B
Hepatitis B can be prevented through vaccination. The hepatitis B vaccine typically is given as a series of three or four injections, administered over the course of six months. The first dose of the vaccine is sometimes called the birth dose, since it frequently is given within the first 24 hours of birth. The vaccine is 90 to 95 percent effective in preventing hepatitis B.
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Causes Of Hepatitis B
Hepatitis B is spread through contact with blood that contains the hepatitis B virus. If infected blood or body fluids enter another persons bloodstream, that person may become infected.
The time from exposure to the hepatitis B virus to the appearance of the illness is 45 to 180 days.
Risky activities that can cause infection include:
- Sharing unsterile or unclean equipment for injecting drugs.
- Piercing the skin with equipment that is not properly cleaned, disinfected and sterilised.
- Sharing razor blades or toothbrushes.
- Coming into contact with infected blood through open cuts or the mucous membranes of another person.
- Having unprotected sex , especially if there is blood present.
Mothers who have hepatitis B can pass the virus to their babies or children at the time of birth or after birth. If the newborn baby is quickly immunised with 2 vaccines, they can be protected from getting hepatitis B.
All blood and blood products produced for medical purposes in Australia are carefully screened for hepatitis B and other blood-borne viruses. The risk of getting infected with hepatitis B from a blood transfusion is extremely low .
When Do You Initiate Hepatitis B Virus Therapy In The Setting Of Hiv
HBV/HIV coinfection represents a significant problem in HIV care. As HAART has improved the prognosis in HIV/AIDS, significant increases in morbidity and mortality due to liver disease have been observed. HBV and HIV are acquired by similar mechanisms and thus coinfection is common. Patients with coinfection of HIV and HBV have higher HBV DNA levels and are less likely to convert from HBeAg+ to HBeAb+, indicating a poorer response to HBV therapy. Patients with a HBV DNA greater than 2000 and F2 or greater fibrosis on biopsy should have HBV treatment. If a patient has cirrhosis, he or she should be treated if HBV DNA is greater than 200. For patients with a high CD4 count, HBV monotherapy that is not active against HIV should be first-line therapy. When initiating HAART, HBV also should be treated with two antiviral agents active against HBV. If CD4 counts are between 350 and 500 cells/mL, one can elect to treat both HIV and HBV. HAART with two agents active against HBV should be used instead of HBV monotherapy in these individuals.
Kyong-Mi Chang, in, 2012
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Impact Of Host Hla Class I Haplotype On Hbv Infection Outcome
GWAS approaches have linked various single-nucleotide polymorphisms in the HLA class II region with a range of infection outcomes, but there is a lack of such robust evidence for the involvement of HLA class I genes . One study identified a relationship between class I HLA-A genotype and HBeAg status , suggesting a role for genes at this locus in control of infection. However, confirmation of HLA associations can be difficult due to the variability in study design and methodologies and the small, heterogeneous populations sampled. Furthermore, the mechanisms for these HLA class I associations with disease outcome are poorly understood. Differences in antigen presentation, TCR binding leading to changes in T cell activation, and altered cytokine production may be responsible, either individually or in combination. Effects of linkage disequilibrium with other important neighboring loci, such as HLA class II or killer-cell immunoglobulin-like receptors genes, cannot be excluded. Functional studies are required to determine the basis for these associations.
Symptoms Of Hepatitis B
Some people who are infected with the hepatitis B virus have mild, flu-like symptoms and some do not become sick at all. Children who are infected are less likely to have an illness or get sick after getting hepatitis B than adults.
In more severe cases, hepatitis B can cause:
- Loss of appetite.
- Pain in the joints.
- Jaundice .
Normally, these health problems disappear in a few weeks, but even when the person feels much better, they may still be infectious.
Most adults who become infected with the hepatitis B virus recover completely and do not become infected again. A few people become very ill in the time just after infection and need to go to hospital some may even die.
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Immunisation For Hepatitis B
Immunisation is the best protection against hepatitis B infection. A course of vaccination is recommended for all babies and people in high-risk groups.
Immunisation can be with a vaccine against hepatitis B alone or with a combination vaccine. To be immunised, contact your doctor or local council.
Protection against hepatitis B is available free of charge under the National Immunisation Program Schedule. In Victoria, immunisation against hepatitis B is free for:
- Babies at birth immunisation against hepatitis B alone as soon as possible after birth.
- Babies at 2, 4 and 6 months combination immunisation in the form of a diphtheria, tetanus, whooping cough, hepatitis B, polio and Haemophilus influenzae type b vaccine .
- Premature babies at 12 months premature babies born under 32 weeks gestation or under 2,000g birth weight receive a single booster dose.
- Children up to and including 9 years of age.
- People aged less than 20 years having a catch-up immunisation.
- Refugees and humanitarian entrants aged 20 years and above.
In Victoria, free hepatitis B vaccine is provided for people who are at increased risk of infection, including:
Immunisation is also recommended, but not necessarily free, for people who are at increased risk of infection, including:
Quantitative Measurement Of Hbv Dna
The assays for HBV infectivity described above were indispensable for HBV research but are too expensive and laborious for the laboratory diagnosis of HB viremia. The best surrogate test is the sensitive and quantitative determination of the number of HBV DNA molecules in plasma or serum. In the early days, the endogenous DNA polymerase reaction developed by Robinson was the first feasible but relatively insensitive and laborious assay. Later this was replaced by various techniques of nucleic acid hybridization using cloned HBV DNA as labeled probes. These techniques were still of insufficient sensitivity and accuracy and could not detect the low viremia of healthy HBsAg carriers or occult HBV infections. They were, however, useful for distinction of high and low infectivity and for HBV monitoring in early therapy studies.
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Who Should Get The Hepatitis B Vaccine
All newborn babies should get vaccinated. You should also get the shot if you:
- Come in contact with infected blood or body fluids of friends or family members
- Use needles to take recreational drugs
- Have sex with more than one person
- Are a health care worker
- Work in a day-care center, school, or jail
How Is Hepatitis B Prevented
Testing & Vaccination
- The hepatitis B vaccine offers excellent protection against HBV. The vaccine is safe and highly effective. Vaccination consists of 3 doses of vaccine over the course of 6 months. Protection lasts for 20 years to life.
- The American Academy of Pediatrics recommends that all children should receive hepatitis B vaccine starting at birth. .
- The CDC recommends hepatitis B vaccine for persons traveling to countries where HBV is common .
- If you have one or more risk factors for hepatitis B infection, you should get a simple HBV blood test. The blood test will determine whether you are:
- immune to hepatitis B or
- susceptible to hepatitis B and need vaccination or
- infected with hepatitis B and need further evaluation by a physician
- California law requires testing of all pregnant women for hepatitis B infection
- If the mother is HBV-infected, she will pass the infection to the baby during the birth process, unless the baby gets immunized within hours of birth
- Giving the infant HBIG and HBV vaccine right away will reliably prevent infection of the infant
- Other family members should best tested for hepatitis B too, and given vaccine if they are not already infected or immune
After Exposure to Hepatitis B
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How Are Infectious Diseases Transmitted
The infectious diseases are spread in the following ways:
When an infected person sneezes or coughs, the droplets containing the pathogen of diseases such as influenza, common cold, etc. might spread in the air and infect others in the vicinity.
Touching an infected person, or their body fluids such as saliva, blood, sweat, urine, etc. transfer the infections to a healthy person, e.g. chickenpox, measles, etc.
Touching the objects or areas touched by an infected person can transfer the infection to a non-infected person and cause diseases.
What Should You Know About Hepatitis B Before You Travel
Hepatitis B is quite common in China and other Asian countries, where as many as 1 in 12 people have the virus, though many dont know it. Before traveling to those places, you should make sure youve been vaccinated against the virus.
In addition to getting the vaccine, you can take these additional precautions to reduce your risk of contracting the virus:
- Refrain from taking illegal drugs.
- Always use latex or polyurethane condoms during sex.
- Make sure new, sterile needles are used during all piercings, tattoos and acupuncture sessions.
- Avoid direct contact with blood and bodily fluids.
- Know the HBV status of all your sexual partners.
- Ask your doctor about possible vaccination before you travel to a place where hepatitis B is common.
A note from Cleveland Clinic
Hepatitis B is a liver disease that can cause serious damage to your health. One reason that is dangerous is that it can easily go undetected for years while damaging your liver. Talk with your healthcare provider about being tested for hepatitis B if you have any reason to believe that you were not vaccinated or if you have engaged in risky behavior. If you do test positive, follow the directions from your healthcare provider so that you can live a longer, healthier and happier life.
Last reviewed by a Cleveland Clinic medical professional on 07/09/2020.
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Section Viii Handling And Storage
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up Footnote 20.
DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism by autoclave, chemical disinfection, gamma irradiation, or incineration before disposing Footnote 20.
STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labeled Footnote 20.
Is Hepatitis Testing Recommended For People With Hiv
Yes. Everyone living with HIV should be tested for HBV and HCV when they are first diagnosed with HIV and begin treatment. People living with HIV who have ongoing risk factors for getting hepatitis B or hepatitis C should be tested annually.
In addition, new HCV screening recommendations from the Centers for Disease Control and Prevention call for:
- One-time screening for all adults 18 years and older
- Screening of all pregnant women during every pregnancy
- Testing for all persons with risk factors, with testing continued periodic testing those with ongoing risk.
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